11th Mediterranean Conference on Medical and Biological Engineering and Computing 2007: MEDICON 2007, 26-30 June 2007, Ljubljana, Slovenia (IFMBE Proceedings)

IFMBE Proceedings Series Editors: R. Magjarevic and J. H. Nagel

Volume 16/1

The International Federation for Medical and Biological Engineering, IFMBE, is a federation of national and transnational organizations representing internationally the interests of medical and biological engineering and sciences. The IFMBE is a non-profit organization fostering the creation, dissemination and application of medical and biological engineering knowledge and the management of technology for improved health and quality of life. Its activities include participation in the formulation of public policy and the dissemination of information through publications and forums. Within the field of medical, clinical, and biological engineering, IFMBE’s aims are to encourage research and the application of knowledge, and to disseminate information and promote collaboration. The objectives of the IFMBE are scientific, technological, literary, and educational. The IFMBE is a WHO accredited NGO covering the full range of biomedical and clinical engineering, healthcare, healthcare technology and management. It is representing through its 58 member societies some 120.000 professionals involved in the various issues of improved health and health care delivery. IFMBE Officers President: Makoto Kikuchi, Vice-President: Herbert Voigt, Past-President: Joachim H. Nagel Treasurer: Shankar M. Krishnan, Secretary-General: Ratko Magjarevic http://www.ifmbe.org

Previous Editions: IFMBE Proceedings MEDICON 2007 “11th Mediterranean Conference on Medical and Biological Engineering and Computing 2007”, Vol. 16, 2007, Ljubljana, Slovenia, CD IFMBE Proceedings BIOMED 2006 “Kuala Lumpur International Conference on Biomedical Engineering”, Vol. 15, 2004, Kuala Lumpur, Malaysia, CD IFMBE Proceedings WC 2006 “World Congress on Medical Physics and Biomedical Engineering”, Vol. 14, 2006, Seoul, Korea, DVD IFMBE Proceedings BSN 2007 “4th International Workshop on Wearable and Implantable Body Sensor Networks”, Vol. 13, 2006, Aachen, Germany IFMBE Proceedings ICBMEC 2005 “The 12th International Conference on Biomedical Engineering”, Vol. 12, 2005, Singapore, CD IFMBE Proceedings EMBEC’05 “3rd European Medical & Biological Engineering Conference, IFMBE European Conference on Biomedical Engineering”, Vol. 11, 2005, Prague, Czech Republic, CD IFMBE Proceedings ICCE 2005 “The 7th International Conference on Cellular Engineering”, Vol. 10, 2005, Seoul, Korea, CD IFMBE Proceedings NBC 2005 “13th Nordic Baltic Conference on Biomedical Engineering and Medical Physics”, Vol. 9, 2005, Umeå, Sweden IFMBE Proceedings APCMBE 2005 “6th Asian-Pacific Conference on Medical and Biological Engineering”, Vol. 8, 2005, Tsukuba, Japan, CD IFMBE Proceedings BIOMED 2004 “Kuala Lumpur International Conference on Biomedical Engineering”, Vol. 7, 2004, Kuala Lumpur, Malaysia IFMBE Proceedings MEDICON and HEALTH TELEMATICS 2004 “X Mediterranean Conference on Medical and Biological Engineering”, Vol. 6, 2004, Ischia, Italy, CD IFMBE Proceedings 3rd Latin – American Congress on Biomedical Engineering “III CLAEB 2004”, Vol. 5, 2004, Joao Pessoa, Brazil, CD IFMBE Proceedings WC2003 “World Congress on Medical Physics and Biomedical Engineering”, Vol. 4, 2003, Sydney, Australia, CD IFMBE Proceedings EMBEC'02 “2nd European Medical and Biological Engineering Conference”, Vol. 3, Parts 1 & 2, 2002, H. Hutten and P. Kroesl (Eds.), Vienna, Austria IFMBE Proceedings 12NBC “12th Nordic Baltic Conference on Biomedical Engineering and Medical Physics”, Vol. 2, 2002, Stefan Sigurdsson (Ed.) Reykjavik, Iceland IFMBE Proceedings MEDICON 2001 – “IX Mediterranean Conference on Medical Engineering and Computing”, Vol. 1, Parts 1 & 2, 2001, R. Magjarevic, S. Tonkovic, V. Bilas, I. Lackovic (Eds.), Pula, Croatia

IFMBE Proceedings Vol. 16/1 T. Jarm, P. Kramar, A. Županič (Eds.)

11th Mediterranean Conference on Medical and Biological Engineering and Computing 2007 MEDICON 2007, 26 – 30 June 2007 Ljubljana, Slovenia

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Editors Tomaž Jarm University of Ljubljana Faculty of Electrical Engineering Trzaska 25 1000 Ljubljana, Slovenia E-Mail: [email protected]

Anže Županič University of Ljubljana Faculty of Electrical Engineering Trzaska 25 1000 Ljubljana, Slovenia E-Mail: [email protected]

Peter Kramar University of Ljubljana Faculty of Electrical Engineering Trzaska 25 1000 Ljubljana, Slovenia E-Mail: [email protected]

Library of Congress Control Number: 2007928834 ISSN: 1680-0737 ISBN: 978-3-540-73043-9 Springer Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable for prosecution under the German Copyright Law. The IFMBE Proceedings is an Offical Publication of the International Federation for Medical and Biological Engineering (IFMBE) Springer is a part of Springer Science+Business Media springer.com © International Federation for Medical and Biological Engineering 2007 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Typesetting: Data supplied by the authors Production: Le-Tex Jelonek, Schmidt & Vöckler GbR Cover design: deblik, Berlin Printed on acid-free paper

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About IFMBE The International Federation for Medical and Biological Engineering (IFMBE) was established in 1959 to provide medical and biological engineering with a vehicle for international collaboration in research and practice of the profession. The Federation has a long history of encouraging and promoting international cooperation and collaboration in the use of science and engineering for improving health and quality of life. The IFMBE is an organization with membership of national and transnational societies and an International Academy. At present there are 52 national members and 5 transnational members representing a total membership in excess of 120 000 worldwide. An observer category is provided to groups or organizations considering formal affiliation. Personal membership is possible for individuals living in countries without a member society The International Academy includes individuals who have been recognized by the IFMBE for their outstanding contributions to biomedical engineering.

Objectives The objectives of the International Federation for Medical and Biological Engineering are scientific, technological, literary, and educational. Within the field of medical, clinical and biological engineering it’s aims are to encourage research and the application of knowledge, and to disseminate information and promote collaboration. In pursuit of these aims the Federation engages in the following activities: sponsorship of national and international meetings, publication of official journals, cooperation with other societies and organizations, appointment of commissions on special problems, awarding of prizes and distinctions, establishment of professional standards and ethics within the field, as well as other activities which in the opinion of the General Assembly or the Administrative Council would further the cause of medical, clinical or biological engineering. It promotes the formation of regional, national, international or specialized societies, groups or boards, the coordination of bibliographic or informational services and the improvement of standards in terminology, equipment, methods and safety practices, and the delivery of health care. The Federation works to promote improved communication and understanding in the world community of engineering, medicine and biology.

Activities Publications of IFMBE include: the journal Medical and Biological Engineering and Computing, the electronic magazine IFMBE News, and the Book Series on Biomedical Engineering. In cooperation with its international and regional conferences, IFMBE also publishes the IFMBE Proceedings Series. All publications of the IFMBE are published by Springer Verlag. The Federation has two divisions: Clinical Engineering and Health Care Technology Assessment. Every three years the IFMBE holds a World Congress on Medical Physics and Biomedical Engineering, organized in cooperation with the IOMP and the IUPESM. In addition, annual, milestone and regional conferences are organized in different regions of the world, such as Asia Pacific, Europe, the Nordic-Baltic and Mediterranean regions, Africa and Latin America. The administrative council of the IFMBE meets once a year and is the steering body for the IFMBE: The council is subject to the rulings of the General Assembly, which meets every three years. Information on the activities of the IFMBE can be found on the web site at: http://www.ifmbe.org.

Foreword It is our great pleasure to welcome you at the11th Mediterranean Conference on Medical and Biological Engineering and Computing – the MEDICON 2007. After 24 years MEDICON conference is coming back to Slovenia, this time into its capital – Ljubljana. The MEDICON conferences are international events of high scientific standards with long lasting tradition held every third year in one of the Mediterranean countries under the auspices of the International Federation for Medical and Biological Engineering. Biomedical engineering today is a well-recognized area of research. It brings together bright minds from diverse disciplines ranging from engineering, physics, and computer sciences on one side to biology and medicine on the other side. With valuable assistance of members of the International Advisory Committee and Scientific Program Committee, the coorganizing institutions and societies, our sponsors, and distinguished invited lecturers we will ensure that the research and development presented at MEDICON 2007 plenary meetings, scientific sessions, and workshops will truly be relevant and up-to-date. MEDICON 2007 is taking place at the premises of University of Ljubljana, Faculty of Electrical Engineering. The choice was obvious: Ljubljana is accessible and vivid, and the academic environment is familiar to all of us. As Ljubljana is located in the centre of the country it offers an excellent opportunity also to explore on your own the remarkable variety of Slovenia’s scenery and national heritage. The Mediterranean coast of Primorska, Alpine resorts of Gorenjska, lovely hills and primeval forests of Dolenjska and the far-reaching plains of Prekmurje are just few examples of regional diversity you can encounter here. All these and other regions of Slovenia are easily accessible from Ljubljana within two hours of driving. We will visit some of our jewels together: Bled and Postojna. We feel confident that you will enjoy MEDICON 2007 both scientifically and socially. We will make every effort to make MEDICON 2007 a memorable event. This is also the place where you will meet your old friends and make new ones. Together we will all face new challenges imposed to us by our society and new technologies. We look forward to meeting you all in Ljubljana. Professor Damijan Miklavcic Organizing Committee The Chairman

Professor Tadej Bajd Slovenian Society of Medical and Biological Engineering, The President

Conference details Name: 11th Mediterranean Conference on Medical and Biological Engineering and Computing Short name: MEDICON 2007 Venue: Ljubljana, SLOVENIA June 26–30, 2007

Proceedings editors Tomaz Jarm Peter Kramar Anze Zupanic

Organized by Slovenian Society for Medical and Biological Engineering

In cooperation with: University of Ljubljana, Faculty of Electrical Engineering http://www.fe.uni-lj.si/ Institute for Rehabilitation of Republic of Slovenia http://www.ir-rs.si/ IFMBE - International Federation for Medical and Biological Engineering http://www.ifmbe.org Institute of Oncology, Ljubljana, Slovenia http://www.onko-i.si/ Jozef Stefan Institute, Ljubljana, Slovenia http://www.ijs.si/ijsw Clinical Center Ljubljana, Slovenia http://www2.kclj.si/ European Federation of Organisations for Medical Physics http://www.efomp.org/ University of Ljubljana, Faculty of Computer and Information Science http://www.fri.uni-lj.si/

University of Maribor, Faculty of Electrical Engineering and Computer Science http://www.feri.uni-mb.si/ podrocje.aspx

Local Organizing Committee Damijan Miklavcic (Chairman) Tadej Bajd Imre Cikajlo Peter Gajsek Tomaz Jarm Tadej Kotnik Peter Kramar Zlatko Matjacic Matjaz Mihelj Anze Zupanic Robert Cugelj Jadran Lenarcic Sasa Markovic Zvonimir Rudolf Tomaz Slivnik Igor Ticar

Scientific Programme Committee Maria Teresa Arredondo (Spain) Janez Bester (Slovenia) Manfred Bijak (Austria) Wolfgang Birkfellner (Austria) Bozidar Casar (Slovenia) Stelios Christofides (Greece) Igor Emri (Slovenia) Carlo Frigo (Italy) Borut Gersak (Slovenia) Milan Gregoric (Slovenia) Francis X. Hart (USA) William Harwin (UK) Ales Iglic (Slovenia) Paolo Inchingolo (Italy) Franc Jager (Slovenia) Joze Jelenc (Slovenia) Rihard Karba (Slovenia) Nada Lavrac (Slovenia) Ratko Magjarevic (Croatia) Crt Marincek (Slovenia)

Roberto Merletti (Italy) Lluis M. Mir (France) Marko Munih (Slovenia) Mustapha Nadi (France) Joachim Nagel (Germany) Eberhard Neumann (Germany) Franjo Pernus (Slovenia) Dejan Popovic (Denmark) Robert Riener (Switzerland) Gregor Sersa (Slovenia) Franc Solina (Slovenia) Vlado Stankovski (Slovenia) Martin Stefancic (Slovenia) Vojko Strojnik (Slovenia) Johannes Struijk (Denmark) Pascal Verdonck (Belgium) Max A. Viergever (Netherlands) Veljko Vlaisavljevic (Slovenia) Damjan Zazula (Slovenia) Ales Zemva (Slovenia) Tatjana Zrimec (Australia) Anton Zupan (Slovenia) Blaz Zupan (Slovenia)

International Advisory Committee Marcello Bracale (Italy) Ivan Bratko (Slovenia) Mario Cifrek (Croatia) David Elad (Israel) Attilio Evangelisti(Italy) Frederique Frouin (France) Enrique J Gomez (Spain) Akos Jobbagy(Hungary) Prodromos Kaplanis (Cyprus) Nicolas Pallikarakis (Greece) Costantinos S. Pattichis (Cyprus) Laura M. Roa (Spain) Herve Saint-Jalmes (France) Mario Forjaz Secca (Portugal) Thomas Sinkjaer (Denmark) Vesna Spasic Jokic (Serbia) Stanko Tonkovic (Croatia) Jos van der Sloten (Belgium) Peter Veltink (Netherlands)

IFMBE Mediterranean Conferences on Medical and Biological Engineering 1977–2007 MEDICON 1977 – I Mediterranean Conference on Medical and Biological Engineering, 12–17 September 1977, Sorrento, Italy MEDICON 1980 – II Mediterranean Conference on Medical and Biological Engineering, 15–19 September 1980, Marseilles, France MEDICON 1983 – III Mediterranean Conference on Medical and Biological Engineering, 5–9 September 1983, Portoroz, Yugoslavia MEDICON 1986 – IV Mediterranean Conference on Medical and Biological Engineering, 9–12 September 1986, Seville, Spain MEDICON 1989 – V Mediterranean Conference on Medical and Biological Engineering, 29 August–1 September 1989, Patras, Greece MEDICON 1992 – VI Mediterranean Conference on Medical and Biological Engineering, 5–10 July 1992, Capri, Italy MEDICON 1995 – VII Mediterranean Conference on Medical & Biological Engineering, 17–21 September 1995, Jerusalem, Israel MEDICON 1998 – VII Mediterranean Conference on Medical & Biological Engineering, 14–17 June 1998, Limassol, Cyprus MEDICON 2001 – IX Mediterranean Conference on Medical Engineering and Computing, 12–15 June 2001, Pula, Croatia MEDICON and HEALTH TELEMATICS 2004, X Mediterranean Conference on Medical and Biological Engineering, 31 July–5 August 2004, Ischia, Italy MEDICON 2007 – XI Mediterranean Conference on Medical Engineering and Computing June 26–30 2007, Ljubljana, Slovenia

Content Invited Lectures EMITEL – an e-Encyclopedia for Medical Imaging Technology......................................................................................... 1 S. Tabakov, C. A. Lewis, A. Cvetkov, M. Stoeva, EMITEL Consortium

Control for Therapeutic Functional Electrical Stimulation.................................................................................................. 3 Dejan B. Popovic, Mirjana B. Popovic

Patient-Cooperative Rehabilitation Robotics in Zurich ........................................................................................................ 7 Robert Riener

From Academy to Industry: Translational Research in Biophysics .................................................................................. 10 R. Cadossi, M.D

Information Technology Solutions for Diabetes management and prevention Current Challenges and Future Research directions............................................................................................................................................. 14 R. Bellazzi

Systemic Electroporation – Combining Electric Pulses with Bioactive Agents................................................................. 18 Eberhard Neumann,

Normal Sessions Analysis of ECG Intelligent Internet Based, High Quality ECG Analysis for Clinical Trials ...................................................................... 22 T.K. Zywietz, R. Fischer

Effects of vagal blockade on the complexity of heart rate variability in rats .................................................................... 26 M. Baumert, E. Nalivaiko and D. Abbott

Assessment of the Heart Rate Variability during Arousal from Sleep by Cohen’s Class Time-Frequency Distributions................................................................................................................. 30 M.O. Mendez , A.M. Bianchi , O.P. Villantieri and S. Cerutti

An algorithm for classification of ambulatory ECG leads according to type of transient ischemic episodes................. 34 A. Smrdel and F. Jager

Phase-Rectified Signal Averaging for the Detection of Quasi-Periodicities in Electrocardiogram ................................. 38 R. Schneider, A. Bauer, J.W. Kantelhardt, P. Barthel and G. Schmidt

Relative contribution of heart regions to the precordial ECG-an inverse computational approach .............................. 42 A.C. Linnenbank, A. van Oosterom, T.F. Oostendorp, P.F.H.M. van Dessel, A.C. van Rossum, R. Coronel, H.L. Tan, J.M.T. de Bakker

Classification Methods for Atrial Fibrillation Prediction after CABG.............................................................................. 46 S. Sovilj, R. Magjarević and G. Rajsman

Modelling effects of Sotalol on Action Potential morphology using a novel Markov model of the HERG channel.............................................................................................................................................................. 50 T.P. Brennan, M. Fink, B. Rodriguez, L.T. Tarassenko

Sample Entropy Analysis of Electrocardiograms to Characterize Recurrent Atrial Fibrillation................................... 54 R. Cervigon, C. Sanchez, J.M. Blas, R. Alcaraz, J. Mateo and J. Millet

USB Based ECG Acquisition System .................................................................................................................................... 58 J. Mihel, R. Magjarevic

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QT Intervals Are Prolonging Simultaneously with Increasing Heart Rate during Dynamical Experiment in Healthy Horses............................................................................................................... 62 P. Kozelek, J. Holcik

FPGA-based System for ECG Beat Detection and Classification ...................................................................................... 66 M. Cvikl and A. Zemva

Feature extraction and selection algorithms in biomedical data classifiers based on time-frequency and principle component analysis. ........................................................................................................................................ 70 P. S. Kostka, E. J. Tkacz

Dynamic Repolarization Assessment and Arrhythmic Risk Stratification........................................................................ 74 E. Pueyo, M. Malik and P. Laguna

Fractal analysis of heart rate variability in COPD patients................................................................................................ 78 G. D’Addio, A. Accardo, G. Corbi, N. Ferrara, F. Rengo

Autonomic Modulation of Ventricular Response by Exercise and Antiarrhythmic Drugs during Atrial Fibrillation ....................................................................................................................................................... 82 VDA Corino, LT Mainardi, D Husser, A Bollmann

Flexible Multichannel System for Bioelectrical Fields Analysis ......................................................................................... 86 P. Kneppo, M. Tysler, K. Hana, P. Smrcka, V. Rosik, S. Karas, E. Heblakova

Neural Networks Based Approach to remove Baseline drift in Biomedical Signals ......................................................... 90 J. Mateo, C. Sanchez, R. Alcaraz, C. Vaya and J. J. Rieta

Non-Linear Organization Analysis of the Dominant Atrial Frequency to Predict Spontaneous Termination of Atrial Fibrillation ............................................................................................................................................................... 94 R. Alcaraz and J. J. Rieta

Using Supervised Fuzzy Clustering and CWT for Ventricular Late Potentials (VLP) Detection in High-Resolution ECG Signal............................................................................................................................................. 99 Ayyoub Jafari, M.H. Morradi

Analysis of Surface EMG An Approach to the Real-Time Surface Electromyogram Decomposition...................................................................... 105 V. Glaser, A. Holobar and D. Zazula

Non-invasive estimation of the degree of motor unit synchronization in the biceps brachii muscle ............................ 109 A. Holobar, M. Gazzoni, D. Farina, D. Zazula, and R. Merletti

EMG Based Muscle Force Estimation using Motor Unit Twitch Model and Convolution Kernel Compensation...... 114 R. Istenic, A. Holobar , R. Merletti and D. Zazula

Model Based Decomposition of Muaps Into Their Constituent Sfeaps............................................................................ 118 M.G. Xyda, C.S. Pattichis, P. Kaplanis, C. Christodoulou and D. Zazula

Fast-Slow phase separation of Near InfraRed Spectroscopy to study Oxigenation v/s sEMG Changes....................... 124 Gian Carlo Filligoi

Analysis of Uterine EMG/EHG Uterine Electromyography in Humans – Contractions, Labor, and Delivery................................................................. 128 R. E. Garfield and W. L. Maner

Predictive value of EMG basal activity in the cervix at initiation of delivery in humans .............................................. 131 D. Rudel, G. Vidmar, B. Leskosek and I. Verdenik

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Evaluation of adaptive filtering methods on a 16 electrode electrohysterogram recorded externally in labor............ 135 J. Terrien, C. Marque, T. Steingrimsdottir and B. Karlsson

Abdominal EHG on a 4 by 4 grid: mapping and presenting the propagation of uterine contractions ......................... 139 B. Karlsson, J. Terrien, V. Gudmundsson, T. Steingrimsdottir and C. Marque

Evaluating Uterine Electrohysterogram with Entropy ..................................................................................................... 144 J. Vrhovec, A. Macek Lebar, D. Rudel

Detection of contractions during labour using the uterine electromyogram................................................................... 148 D. Novak, A. Macek-Lebar, D. Rudel and T. Jarm

Artificial Intelligence and Intelligent Data Analysis in Medicine GIFT: a tool for generating free text reports from encoded data..................................................................................... 152 Silvia Panzarasa, Silvana Quaglini, Mauro Pessina, Anna Cavallini, Giuseppe Micieli

Supporting Factors to Improve the Explanatory Potential of Contrast Set Mining: Analyzing Brain Ischaemia Data......................................................................................................................................... 157 N. Lavrac, P. Kralj, D. Gamberger and A. Krstacic

Availability Humanization - The Semantic Model in Occupational Health .................................................................... 162 M. Molan and G. Molan

Analyzing Distributed Medical Databases on DataMiningGrid© .................................................................................... 166 Vlado Stankovski, Martin Swain, Matevz Stimec and Natasa Fidler Mis

Bioimpedance FENOTIP: Microfluidics and Nanoelectrodes for the Electromagnetic Spectroscopy of Biological Cells ................... 170 V. Senez, A. Treizebré, E. Lennon, D. Legrand, H. Ghandour, B. Bocquet, T. Fujii and J. Mazurier

Impedance method for determination of the root canal length ........................................................................................ 174 D. Krizaj, J. Jan and T. Zagar

Separation of electroporated and non-electroporated cells by means of dielectrophoresis ........................................... 178 J. Oblak, D. Krizaj, S. Amon, A. Macek-Lebar and D. Miklavcic

A simple DAQ-card based bioimpedance measurement system....................................................................................... 182 T. Zagar and D. Krizaj

Bioimpedance spectroscopy of human blood at low frequency using coplanar microelectrodes .................................. 186 J. Prado, M. Nadi, C. Margo and A Rouane

Impedance Spectroscopy of Newt Tails .............................................................................................................................. 190 F.X. Hart, J.H. Johnson and N.J. Berner

Dielectric properties of water and blood samples with glucose at different concentrations .......................................... 194 A. Tura, S. Sbrignadello, S. Barison, S. Conti, G. Pacini

Parameter Optimization in Voltage Pulse Plethysmography............................................................................................ 198 M. Melinscak

Inherently Synchronous Data Acquisition as a Platform for Bioimpedance Measurement........................................... 202 G. Poola and J. Toomessoo

Benefits and disadvantages of impedance-ratio measuring method in new generation of apex-locators ..................... 206 T. Marjanovic, Z. Stare

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Biological Effects of Electromagnetic Radiation Effect of Modulated 450 MHz Microwave on HumanEEG at Different Field Power Densities .................................... 210 R. Tomson, H.Hinrikus, M. Bachmann, J. Lass, and V. Tuulik

Regenerative Effects of (-)-epigallocatechin-gallate Against Hepatic Oxidative Stress Resulted by Mobile Phone Exposure .................................................................................................................................................. 214 E. Ozgur, G. Güler and N. Seyhan

Conducting Implant in Low Frequency Electromagnetic Field ....................................................................................... 218 B. Valic, P. Gajsek and D.Miklavcic

Measurements of background electromagnetic fields in human environment................................................................ 222 T. Trcek, B. Valic and P. Gajsek

Numerical Assessment of Induced Current Densities for Pregnant Women Exposed to 50 Hz Electromagnetic Field............................................................................................................................................ 226 A. Zupanic, B. Valic and D. Miklavcic

The Relation Assessment Between 50 Hz Electric Field Exposure-Induced Protein Carbonyl Levels and The Protective Effect of Green Tea Catechin (EGCG) .............................................................................................. 230 A. Tomruk, G. Guler and N. Seyhan

EMF Monitoring Campaign in Slovenian Communes ...................................................................................................... 234 B. Valic, J. Jancar and P. Gajsek

Biomaterials Surface modification of titanium fiber-mesh scaffolds through a culture of human SAOS-2 osteoblasts electromagnetically stimulated ............................................................................................................................................ 238 L. Fassina, L. Visai, E. Saino, M.G. Cusella De Angelis, F. Benazzo and G. Magenes

Expression of Smooth Muscle Cells Grown on Magnesium Alloys .................................................................................. 242 S.K. Lu, W.H. Lee, T.Y. Tian, C.H. Chen, H.I. Yeh

Coalescence of phospholipid vesicles mediated by β2GPI – experiment and modelling ................................................ 246 J. Urbanija, B. Rozman, A. Iglič, T. Mareš, M. Daniel, Veronika Kralj-Iglič

Advancing in the quality of the cells assigned for Autologous Chondrocyte Implantation (ACI) method ................... 249 A. Barlic, D. Radosavljevic, M. Drobnic and N. Kregar-Velikonja

Mesenchymal Stem Cells: a Modern Approach to Treat Long Bones Defects................................................................ 253 H. Krečič-Stres, M. Krkovič, J. Koder, E. Maličev, M. Drobnič, D. Marolt and N. Kregar-Velikonja

Biomechanics Combination of microfluidic and structure-continual studies in biorheology of blood with magnetic additions ........ 257 E.Yu. Taran, V.A. Gryaznova and O.O. Melnyk

Virtual Rehabilitation of Lower Extremities...................................................................................................................... 262 T. Koritnik, T. Bajd and M. Munih

Rating Stroke Patients Based on Movement Analysis ....................................................................................................... 266 A. Jobbagy, G. Fazekas

Bending stiffness of odontoid fracture fixation with one cortical screw – numerical approach .................................... 270 L. Capek, P. Buchvald

Elastic Moduli and Poisson’s Ratios of Microscopic Human Femoral Trabeculae ........................................................ 274 J. Hong, H. Cha, Y. Park, S. Lee, G. Khang,and Y. Kim

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The Dissipation of Suction Waves in Flexible Tubes ......................................................................................................... 278 J. Feng and A.W. Khir

Hip stress distribution may be a risk factor for avascular necrosis of femoral head...................................................... 282 D. Dolinar, M. Ivanovski, I. List, M. Daniel, B. Mavcic, M. Tomsic, A. Iglic and V. Kralj-Iglic

Elasticity Distribution Imaging of Sliced Liver Cirrhosis and Hepatitis using a novel Tactile Mapping System........ 286 Y. Murayama, T. Yajima, H. Sakuma, Y. Hatakeyama, C.E. Constantinou, S. Takenoshita, S. Omata

Changes in Biomechanics Induced by Fatigue in Single-leg Jump and Landing............................................................ 288 J. Stublar, P. Usenik, R. Kamnik, M. Munih

Musculoskeletal Modeling to Provide Muscles and Ligaments Length Changes during Movement for Orthopaedic Surgery Planning...................................................................................................................................... 292 C.A. Frigo and E.E. Pavan

Numerical model of a myocyte for the evaluation of the influence of inotropic substances on the myocardial contractility............................................................................................................................................ 296 Bernardo Innocenti, Andrea Corvi

Biomechanical Analysis of Bolus Processing ...................................................................................................................... 300 T. Goldmann, S. Konvickova and L. Himmlova

Application of Simplified Ray Method for the Determination of the Cortical Bone Elastic Coefficients by the Ultrasonic Wave Inversion ....................................................................................................................................... 304 T. Goldmann, H. Seiner and M. Landa

Model for Muscle Force Calculation Including Dynamics Behavior and Vicoelastic Properties of Tendon................ 308 M. Vilimek

Biomedical Engineering Education and E-learning New courses in medical engineering, medical physics and bio/physics for clinical engineers, medicine and veterinary medicine specialists in Serbia..................................................................................................................... 310 V. M. Spasic-Jokic, D. Lj. Popovic, S. Stankovicand I. Z. Zupunski

The Education and Training of the Medical Physicist in Europe The European Federation of Organisations for Medical Physics -EFOMP Policy Statements and Efforts......................................................................................... 313 S. Christofides, T. Eudaldo, K. J. Olsen, J. H. Armas, R. Padovani, A. Del Guerra, W. Schlegel, M. Buchgeister, P. F. Sharp

Assessment of a system developed for virtual teaching ..................................................................................................... 319 M.L.A.Botelho, D.F.Cunha, F.B.Mendonca and S.J.Calil

A Web-Based E-learning Application on Electrochemotherapy ...................................................................................... 323 S. Corovic, J. Bester, A. Kos, M. Papic and D. Miklavcic

The value of clinical simulation-based training.................................................................................................................. 327 Vesna Paver-Erzen, Matej Cimerman

Biomedical Engineering and Virtual Education ................................................................................................................ 329 A. Kybartaite, J. Nousiainen, K. Lindroos, J. Malmivuo

Presentation of Cochlear Implant to Deaf People .............................................................................................................. 332 J. Vrhovec, A. Macek Lebar , D. Miklavcic, M. Eljon and J. Bester

Internet Examination – A New Tool in e-Learning ........................................................................................................... 336 J.A. Malmivuo, K. Lindroos and J.O. Nousiainen

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Biomedical Instrumentation and Measurement Development of a calibration bath for clinical thermometers .......................................................................................... 338 I. Pusnik, J. Bojkovski and J. Drnovsek

Evaluation of non-invasive blood pressure simulators ...................................................................................................... 342 G. Gersak and J. Drnovsek

Development of Implantable SAW Probe for Epilepsy Prediction .................................................................................. 346 N. Gopalsami, I. Osorio, S. Kulikov, S. Buyko, A. Martynov and A.C. Raptis

Accurate On-line Estimation of Delivered Dialysis Dose by Dialysis Adequacy Monitor (DIAMON) ......................... 350 I. Fridolin, J. Jerotskaja, K. Lauri, A.Scherbakovand M. Luman

Clinical implication of pulse wave analysis......................................................................................................................... 354 R. Accetto, K. Rener, J. Brguljan-Hitij, B. Salobir

Ambulatory blood pressure monitoring is highly sensitive for detection of early cardiovascular risk factors in young adults.......................................................................................................... 357 Maja Benca, Ales Zemva, Primoz Dolenc

Simple verification of infrared ear thermometers by use of fixed-point.......................................................................... 361 J. Bojkovski

Control Abilities of Power and Precision Grasping in Children of Different Ages ........................................................ 365 B. Bajd and L. Praprotnik

Bluetooth Portable Device for Continuous ECG and Patient Motion Monitoring During Daily Life .......................... 369 P. Bifulco, G. Gargiulo, M. Romano, A. Fratini and M. Cesarelli

Wearable Wireless Biopotential Electrode for ECG Monitoring ..................................................................................... 373 E.S. Valchinov and N.E. Pallikarakis

Modelling and Simulation of Ultrasound Non Linearities Measurement for Biological Mediums ............................... 377 R. Guelaz, D. Kourticheand M. Nadi

A Personal Computer as a Universal Controller for Medical-Focused Appliances........................................................ 381 Denis Pavliha, Matej Rebersek, Luka Krevs and Damijan Miklavcic

System Identification of Integrative Non Invasive Blood Pressure Sensor Based on ARMAX Estimator Algorithm ....................................................................................................................................... 385 Noaman M. Noaman, Abbas K. Abbas

Experimental Measurements of Potentials Generated by the Electrodes of a Cochlear Implant in a Phantom.......... 390 G. Tognola, A. Pesatori, M. Norgia, F. Sibella, S. Burdo, C. Svelto, M. Parazzini, A. Paglialonga, P. Ravazzani

Evaluation of muscle dynamic response measured before and after treatment of spastic muscle with a BTX-A − A case study ............................................................................................................................................... 393 D. Krizaj, K. Grabljevec, B. Simunic

Home Care Technologies for Ambient Assisted Living..................................................................................................... 397 Ratko Magjarevic

Development of the ISO standard for clinical thermometers ........................................................................................... 401 I. Pusnik

Hardware optimization of a Real-Time Telediagnosis System .......................................................................................... 405 Muhammad Kamrul Hasan, Md. Nazmus Sayadat, and Md. Atiqur Rahman Sarker

Application of time-gated, intensified CCD camera for imaging of absorption changes in non-homogenous medium. ............................................................................................................................................... 410 P. Sawosz, M. Kacprzak, A. Liebert, R. Maniewski

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The impact of the intubation model upon ventilation parameters ................................................................................... 413 B. Stankiewicz, J. Glapinski, M. Rawicz, B. Woloszczuk-Gebicka, M. Michnikowski, M. Darowski

The hybrid piston model of lungs ........................................................................................................................................ 416 M. Kozarski, K. Zielinski, K.J. Palko and M. Darowski

Biomedical Signal Processing Estimation of Neural Noise Spectrum in a Postural Control Model ................................................................................ 419 A.F. Kohn

Optimized Design of Single-sided Quadratic Phase Outer Volume Suppression Pulses for Magnetic Resonance Imaging ........................................................................................................................................ 423 N. Stikov, A. Mutapcic and J.M. Pauly

Analysis of foveation duration and repeatability at different gaze positions in patients affected by congenital nystagmus ...................................................................................................................................................... 426 M. Cesarelli, P. Bifulco, M. Romano, G. Pasquariello, A. Fratini, L. Loffredo, A. Magli, T . De Berardinis, D. Boccuzzi

Frequency characteristics of arterial catheters – an in vitro study .................................................................................. 430 F. T. Molnar and G. Halasz

Signal Processing methods for PPG Module to Increase Signal Quality ......................................................................... 434 K. Pilt, K. Meigas, J. Lass and M. Rosmann

Detection of the cancerous tissue sections in the breast optical biopsy dataflow using neural networks...................... 438 A. Nuzhny, S. Shumsky, T. Lyubynskaya

On the Occurrence of Phase-locked Pulse Train in the Peripheral Auditory System .................................................... 442 T. Matsuoka, D. Konno and M. Ogawa

A device for quantitative kinematic analysis of children’s handwriting movements...................................................... 445 A. Accardo, A. Chiap, M. Borean, L. Bravar, S. Zoia, M. Carrozzi and A. Scabar

Blood Flow and Oxygenation Measurement Monitoring of preterm infants during crying episodes...................................................................................................... 449 L. Bocchi, L. Spaccaterra, F. Favilli, L. Favilli, E. Atrei, C. Manfredi and G. P. Donzelli

Measuring Tumor Oxygenation by Electron Paramagnetic Resonance Oximetry in vivo............................................. 453 Z. Abramovic, M. Sentjurc and J. Kristl

Radiotracer and Microscopic Assessment of Vascular Function in Cancer Therapy .................................................... 457 G.M. Tozer and V.J. Cunningham

The Influence of Endurance Training on Brain and Leg Blood Volumes Translocation During an Orthostatic Test ............................................................................................................................................................... 461 A. Usaj

Comparison of two hypoxic markers: pimonidazole and glucose transporter 1 (Glut-1) .............................................. 465 A. Coer, M. Legan, D. Stiblar-Martincic, M. Cemazar, G. Sersa

Effects of vinblastine on blood flow of solid tumours in mice ........................................................................................... 469 S. Kranjc, T. Jarm, M. Cemazar, G. Sersa, A. Secerov, M. Auersperg

Automatic recognition of hemodynamic responses to rare stimuli using functional Near-Infrared Spectroscopy...... 473 M. Butti, A. C. Merzagora, M. Izzetoglu, S. Bunce, A. M. Bianchi, S. Cerutti, B. Onaral

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Brain Research and Analysis of EEG Brain on a Chip: Engineering Form and Function in Cultured Neuronal Networks..................................................... 477 B.C. Wheeler

Identification of Gripping-Force Control from Electroencephalographic Signals ......................................................... 478 A. Belic, B. Koritnik, V. Logar, S. Brezan, V. Rutar, R. Karba, G. Kurillo and J. Zidar

Quantitative EEG as a Diagnostic Tool in Patients with Head Injury and Posttraumatic Epilepsy............................. 482 T. Bojic, B. Ljesevic, A. Dragin, S. Jovic, L Schwirtlich, A. Stefanovic

BSI versus the Eye: EEG Monitoring in Carotid Endarterectomy.................................................................................. 487 W.A. Hofstraand M.J.A.M. van Putten

Assessing FSP Index Performance as an Objective MLAEP Detector during Stimulation at Several Sound Pressure Levels ........................................................................................................................................ 492 M. Cagy, A.F.C. Infantosi and E.J.B. Zaeyen

The Colorful Brain: Compact Visualisition of Routine EEG Recordings ....................................................................... 497 Michel J.A.M. van Putten

Using ANN on EEG signals to predict working memory task response .......................................................................... 501 V. Logar, A. Belic, B. Koritnik S. Brezan, V. Rutar, J. Zidar, R. Karba and D. Matko

Comparison of methods and co-registration maps of EEG and fMRI in Occipital Lobe Epilepsy............................... 505 M. Forjaz Secca, A. Leal, J. Cabraland H. Fernandes

Multimodal imaging issues for electric brain activity mapping in the presence of brain lesions .................................. 509 F. Vatta, P. Bruno, F. Di Salle, F. Meneghini, S. Mininel and P. Inchingolo

Proposal and validation of a framework for High Performance 3D True Electrical Brain Activity Mapping ............ 513 S. Mininel, P. Bruno, F. Meneghini, F. Vatta and P. Inchingolo

EEG Peak Alpha Frequency as an Indicator for Physical Fatigue .................................................................................. 517 S.C. Ng, P. Raveendran

Acetylcholine addition and electrical stimulation of dissociated neurons from an extended subthalamic area – A pilot study in the rat.......................................................................................................................................................... 521 T. Heida, K.G. Usunoff and E. Marani

Cross-correlation based methods for estimating the functional connectivity in populations of cortical neurons........ 525 A.N. Ide, M. Chiappalone , L. Berdondini , V. Sanguineti , S. Martinoia

Movement Related Potentials in Spontaneous and Provoked Thumb Movement .......................................................... 529 A.B. Sefer, M. Krbot, V. Isgum and M. Cifrek

Cardiovascular System Simulation of Renal Artery Stenosis Using Cardiovascular Electronic System.............................................................. 533 K.Hassani, M.Navidbakhsh and M.Rostami

Extracellular ATP-Purinoceptor Signaling for the Intercellular Synchronization of Intracellular Ca oscillation in Cultured Cardiac Myocytes.......................................................................................... 537 K. Kawahara and Y. Nakayama

Computer Assisted Optimization of Biventricular Pacing Assuming Ventricular Heterogeneity................................. 541 R. Miri, M. Reumann, D. Farina , B. Osswald, O. Dössel

Power density spectra of the velocity waveforms in Artificial heart valves..................................................................... 545 A. A. Sakhaeimanesh

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Medical Plans as a Middle Step in Building Heart Failure Expert System ..................................................................... 549 Alan Jovic, Marin Prcela and Goran Krstacic

Method for Reducing Pacing Current Threshold at Transesophageal Stimulation ....................................................... 554 A. Anier, J. Kaik and K. Meigas

User–centered system to manage Heart Failure in a mobile environment ...................................................................... 558 E. Villalba, D. Salvi, M. Ottaviano, I. Peinado, M. T. Arredondo, M. Docampo

Comparison of Four Calculation Techniques for Estimation of Local Arterial Compliance ........................................ 562 R. Raamat, J. Talts and K. Jagomägi

The Effect of in vitro Anticoagulant Disodium Citrate on Beta-2-glycoprotein I - Induced Coalescence of Giant Phospholipid Vesicles ............................................................................................................................................ 566 M. Frank, M. Lokar, J. Urbanija, M. Krzan, V. Kralj-Iglic, B. Rozman

Electroporation Based Therapies Cell membrane fluidity at different temperatures in relation to electroporation effectiveness of cell line V79 ........... 570 Masa Knaduser, Marjeta Sentjurcand Damijan Miklavcic

Voltage commutator for multiple electrodes in gene electrotransfer of skin cells .......................................................... 574 M. Kranjc, P. Kramar, M. Rebersek and D. Miklavcic

Voltage breakdown measurement of planar lipid bilayer mixtures ................................................................................. 578 P. Kramar, D. Miklavcic and A. Macek Lebar

Antitumor effectiveness of electrotransfer of p53 into murine sarcomas alone or combined with electrochemotherapy using cisplatin........................................................................................................................... 582 M. Cemazar, A. Grosel, S. Kranjc, and G. Sersa

Electrochemotherapy in veterinary medicine .................................................................................................................... 586 Natasa Tozon and Maja Cemazar

Tumor electrotransfection progress and prospects: the impact of knowledge about tumor histology ......................... 589 S. Mesojednik, D. Pavlin, G. Sersa, A. Coer, S. Kranjc, A. Grosel, G. Tevz, M. Cemazar

Quantification of ion transport during cell electroporation – theoretical and experimental analysis of transient and stable pores during cell electroporation.................................................................................................. 593 M. Pavlin, and D. Miklavcic

A numerical model of skin electroporation as a method to enhance gene transfection in skin...................................... 597 N. Pavselj, V. Preat and D. Miklavcic

Tumor blood flow modifying and vascular disrupting effect of electrochemotherapy................................................... 602 G. Sersa, M. Cemazar, S. Kranjc and D. Miklavcic

Real time electroporation control for accurate and safe in vivo electrogene therapy..................................................... 606 David Cukjati, Danute Batiuskaite, Damijan Miklavčič, Lluis M. Mir

Electrochemotherapy of equids cutaneous tumors: a 57 case retrospective study 1999-2005 ....................................... 610 Y. Tamzali, J. Teissie, M. Golzioand M. P. Rols

Electrochemotherapy in treatment of solid tumours in cancer patients .......................................................................... 614 G. Sersa for the ESOPE group

Electropulsation, an biophysical delivery method for therapy ......................................................................................... 618 J. Teissie and M. Cemazar

Bases and rationale of the electrochemotherapy................................................................................................................ 622 L.M. Mir

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A critical step in gene electrotransfer: the injection of the DNA...................................................................................... 623 F.M. André and L.M. Mir

In vivo imaging of siRNA electrotransfer and silencing in different organs ................................................................... 624 A. Paganin-Gioanni, J.M. Escoffre, L. Mazzolini, M.P. Rols, J. Teissiéand M. Golzio

An endoscopic system for gene & drug delivery directly to intraluminal tissue. ............................................................ 628 D.M. Soden, M. Sadadcharam, J. Piggott,A. Morrissey, C.G. Collins and G.C. O’Sullivan.

The effects of irreversible electroporation on tissue, in vivo............................................................................................. 629 Boris Rubinsky

Equine Cutaneous Tumors Treatment by Electro-chemo-immuno-geno-therapy ......................................................... 630 Y. Tamzali, B. Couderc, M.P. Rols, M. Golzio and J. Teissie

Analysis of Tissue Heating During Electroporation Based Therapy: A 3D FEM Model for a Pair of Needle Electrodes.............................................................................................................................................................. 631 I. Lackovic, R. Magjarevic and D. Miklavcic

The induced transmembrane potential and effective conductivity of cells in dense cell system .................................... 635 M. Pavlin, and D.Miklavcic

An experimental and numerical study of the induced transmembrane voltage and electroporation on clusters of irregularly shaped cells ................................................................................................................................. 639 G. Pucihar, T. Kotnik, and D. Miklavcic

Functional Electrical and Magnetic Stimulation The effect of afferent training on long-term neuroplastic changes in the human cerebral cortex ................................ 643 R.L.J. Meesen, O. Levin and S.P. Swinnen

An Experimental Test of Fuzzy Controller Based on Cycle-to-Cycle Control for FES-induced Gait: Knee Joint Control with Neurologically Intact Subjects................................................................................................... 647 T. Watanabe, A. Arifin, T. Masuko and M. Yoshizawa

Troubleshooting for DBS patients by a non-invasive method with subsequent examination of the implantable device...................................................................................................................................................... 651 H. Lanmüller, J. Wernisch and F. Alesch

Treating drop-foot in hemiplegics: the role of matrix electrode....................................................................................... 654 C. Azevedo-Coste, G. Bijelic, L. Schwirtlich and D.B. Popovic

FES treatment of lower extremities of patients with upper / lower motor neuron lesion: A comparison of rehabilitation strategies and stimulation equipment.................................................................................. 658 M. Bijak, M. Mödlin, C. Hofer, M. Rakos, H. Kern, W. Mayr

Optimal Control of Walking with Functional Electrical Stimulation: Inclusion of Physiological Constraints............ 661 Strahinja Dosen, Dejan B. Popovic

Magnetic Coils Design for Localized Stimulation .............................................................................................................. 665 L. Cret, M. Plesa, D. Stet and R.V. Ciupa

Gait and Motion Analysis Vertical unloading produced by electrically evoked withdrawal reflexes during gait: preliminary results................. 669 J. Emborg, E. Spaichand O.K. Andersen

Two-level control of bipedal walking model....................................................................................................................... 673 A. Olensek and Z. Matjacic

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Data mining time series of human locomotion data based on functional approximation............................................... 677 V. Ergovic, S. Tonkovic V. Medved and M. Kasovic

Kinematic and kinetic patterns of walking in spinal muscular atrophy, type III ........................................................... 681 Z. Matjacic, A. Praznikar, A. Olensek, J. Krajnik, I. Tomsic, M. Gorisek-Humar, A. Klemen, A. Zupan

The Gait E-Book – Development of Effective Participatory Learning using Simulation and Active Electronic Books ................................................................................................................................................ 685 A. Sandholm, P. Fritzson, V. Arora, Scott Delp, G. Petersson and J. Rose

A Study on Sensing System of Lower Limb Condition with Piezoelectric Gyroscopes: Measurements of Joint Angles and Gait Phases................................................................................................................. 689 Norio Furuse and Takashi Watanabe

Health Care and Medical Informatics A standard tool to interconnect clinical, genomic and proteomic data for personalization of cardiac disease treatment................................................................................................................................................. 693 M. Giacomini, F. Lorandi and C. Ruggiero

How do physicians make a decision?................................................................................................................................... 696 Kaiser Niknam, Mahdi Ghorbani Samini, Hedyeh Mahmudi, Sahar Niknam

Informational Internet-systems in Ukrainian healthcare – problems and perspectives................................................. 700 A.A. Lendyak

Reducing time in emergency medical service by improving information exchange among information systems........ 704 A. Jelovsek, M. Stern

Data Presentation Methods for Monitoring a Public Health-Care System ..................................................................... 708 Aleksander Pur, Marko Bohanec, Nada Lavrač, Bojan Cestnik

Adaptive Altered Auditory Feedback (AAF) device based on a multimodal intelligent monitor to treat the permanent developmental stuttering (PDS): A critical proposal ............................................................................... 712 Manuel Prado, Laura M. Roa

Simulation in Medicine and Nursing – First Experiences in Simulation centre at Faculty of Health Sciences University of Maribor........................................................................................................................... 716 D. Micetic-Turk, M. Krizmaric, H. Blazun, N. Krcevski-Skvarc, A. Kozelj, P. Kokol, Š. Grmec, Z. Turk

Open Source in Health Care: a milestone toward the creation of an ICT-based pan-European health facility .......... 719 D. Dinevski, P. Inchingolo, I. Krajnc, P. Kokol

The Open Three Consortium: an open-source, full-service-based world-wide e-health initiative ................................ 723 P. Inchingolo, M. Beltrame, P. Bosazzi, D. Dinevski G. Faustini, S. Mininel, A. Poli, F. Vatta

O3-RWS: a Java-based, IHE-compliant open-source radiology workstation ................................................................. 727 G. Faustini, P. Inchingolo

O3-DPACS: a Java-based, IHE compliant open-source data and image manager and archiver.................................. 732 M. Beltrame, P. Bosazzi, A. Poli, P. Inchingolo

GATEWAY: Assistive Technology for Education and Employment............................................................................... 737 D. Kervina, M. Jenko, M. Pustisek and J. Bester

Reshaping Clinical Trial Data Collection Process to Use the Advantages of the Web-Based Electronic Data Collection...................................................................................................................................................................... 741 I. Pavlovic and I. Lazarevic

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Telepathology: Success or Failure? ..................................................................................................................................... 745 D. Giansanti, L. Castrichella and M. R. Giovagnoli

E-learning for Laurea in Biomedical laboratory Technicians: a feasibility study .......................................................... 749 D. Giansanti, L. Castrichella and M.R. Giovagnoli

Health Care Technology Assessment and Management A hospital structural and technological performance indicators set................................................................................ 752 E. Iadanza, F. Dori and G. Biffi Gentili, G. Calani, E. Marini, E. Sladoievich, A. Surace

Continuous EEG monitoring in the Intensive Care Unit: Beta Scientific and Management Scientific aspects ........... 756 P.M.H. Sanders, M.J.A.M. van Putten

Technology Assessment for evaluating integration of Ambulatory Follow-up and Home Monitoring......................... 758 L. Pecchia, L. Bisaccia, P. Melillo, L. Argenziano, M. Bracale

A Multi Scale Methodology for Technology Assessment. A case study on Spine Surgery ............................................. 762 L. Pecchia, F. Acampora and S. Acampora, M. Bracale

Heart Rate Analysis Complexity Analysis of Heart Rate Control Using Symbolic Dynamics in Young Diabetic Patients ........................... 766 M. Javorka, Z. Trunkvalterova, I. Tonhajzerova, J. Javorkova and K. Javorka

Recurrence Quantification Analysis of Heart Rate Dynamics in Young Patients with Diabetes Mellitus.................... 769 Z. Trunkvalterova, M. Javorka, I. Tonhajzerova, J. Javorkova, and K. Javorka

Joint Symbolic Dynamic of Cardiovascular Time Series of Rats ..................................................................................... 773 D. Varga,T. Loncar-Turukalo, D.Bajic, S. Milutinovic, N. Japundzic-Zigon

Technical problems in STV indexes application ................................................................................................................ 777 M. Cesarelli, M. Romano, P. Bifulco

2CTG2: A new system for the antepartum analysis of fetal heart rate............................................................................ 781 G. Magenes, M.G. Signorini, M. Ferrario, F. Lunghi

Speeding up the Computation of Approximate Entropy................................................................................................... 785 G. Manis and S. Nikolopoulos

Cardiac arrhythmias and artifacts in fetal heart rate signals: detection and correction ............................................... 789 M. Cesarelli, M. Romano, P. Bifulco, A. Fratini

Medical Imaging Artery movement tracking in angiographic sequences for coronary flow calculation ................................................... 793 Hanna Goszczynska

Battery powered and wireless Electrical Impedance Tomography Spectroscopy Imaging using Bluetooth................ 798 A.L. McEwan and D.S. Holder

Using Heuristics for the Lung Fields Segmentation in Chest Radiographs..................................................................... 802 D. Gados and G. Horvath

Sampling Considerations and Resolution Enhancement in Ideal Planar Coded Aperture Nuclear Medicine Imaging ................................................................................................................................................................. 806 D.M. Starfield, D.M. Rubin and T. Marwala

Measuring Red Blood Cell Velocity with a Keyhole Tracking Algorithm....................................................................... 810 C.C. Reyes-Aldasoro, S. Akerman and G.M. Tozer

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Web-based Visualization Interface for Knee Cartilage..................................................................................................... 814 C.-L. Poh, R.I. Kitney and R.B.K. Shrestha

Markov Chain Based Edge Detection Algorithm for Evaluation of Capillary Microscopic Images............................. 818 G. Hamar, G. Horvath, Zs. Tarjan and T. Virag

Lung Surface Classification on High-Resolution CT using Machine Learning .............................................................. 822 S. Busayarat and T. Zrimec

Evaluation of Tomographic Reconstruction for Small Animals using micro Digital Tomosynthesis (microDTS)............................................................................................................................................................................ 826 D. Soimu, Z. Kamarianakis and N. Pallikarakis

Methods for Automatic Honeycombing Detection in HRCT images of the Lung........................................................... 830 T. Zrimec and J. Wong

Stochastic Rank Correlation - A novel merit function for dual energy 2D/3D registration in image-modulated radiation therapy .................................................................................................................................................................. 834 W. Birkfellner

Evaluation of peptides tagged nanoparticle adhesion to activated endothelial cells....................................................... 835 K. Rhee, H.J.Moon, K.S. Park and G. Khang

Estimation method for brain activities are influenced by blood pulsation effect............................................................ 839 W. H. Lee, J. H. Ku, H. R. Lee, K. W. Han, J. S. Park, J. J. Kim, I. Y. Kim, and S. I. Kim

Classification of Prostatic Tissues using Feature Selection Methods ............................................................................... 843 S. Bouatmane, B. Nekhoul, A. Bouridane and C. Tanougast

Texture Classification of Retinal Layers in Optical Coherence Tomography................................................................. 847 M. Baroni, S. Diciotti , A. Evangelisti, P. Fortunato and A. La Torre

Automatic cell detection in phase-contrast images for evaluation of electroporation efficiency in vitro ................................................................................................................................... 851 Marko Usaj, Drago Torkar, Damijan Miklavcic

Medical Physics Scattered radiation spectrum analysis for the breast cancer diagnostics ........................................................................ 856 S.A. Belkov, G.G. Kochemasov, N.V. Maslov, S.V. Bondarenko, N.M. Shakhova, I.Yu. Pavlycheva, A. Rubenchik, U. Kasthuri, L.B. Da Silva

Laminar Axially Directed Blood Flow Promotes Blood Clot Dissolution: Mathematical Modeling Verified by MR Microscopy................................................................................................................................................................ 859 J. Vidmar, B. Grobelnik, U. Mikac, G. Tratar, A. Blinc and I. Sersa

Snoring and CT Imaging...................................................................................................................................................... 864 I. Fajdiga, A. Koren and L. Dolenc

Modulation of the beam intensity with wax filter compensators...................................................................................... 867 D. Grabec and P. Strojan

A Model of Flow Mechanical Properties of the Lung and Airways ................................................................................. 871 B. Kuraszkiewicz, T. Podsiadly-Marczykowska and M. Darowski

Standard versus 3D optimized MRI-based planning for uterine cervix cancer brachyradiotherapy – The Ljubljana experience .................................................................................................................................................... 875 R. Hudej, P. Petric, J. Burger

Problems faced after the transition from a film to a DDR Radiology Department ........................................................ 879 S.P. Spyrou,I. Gerogiannis, A.P. Stefanoyiannis, S. Skannavis, A. Kalaitzis, P.A. Kaplanis

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Verification of planned relative dose distribution for irradiation treatment technique using half-beams in the area of field abutment ................................................................................................................................................ 883 R. Hudej

Experimental verification of the calculated dose for Stereotactic Radiosurgery with specially designed white polystyrene phantom .......................................................................................................... 887 B. Casar, A. Sarvari

In vivo dosimetry with diodes in radiotherapy patients treated with four field box technique ..................................... 891 A. Strojnik

The Cavitational Potential of a Single-leaflet Virtual MHV: A Multi-Physics and Multiscale Modelling Approach ................................................................................................................................... 895 D. Rafiroiu, V. Díaz-Zuccarini, D.R. Hose, P.V. Lawford, A.J. Narracott, R.V. Ciupa

Wavelet-based quantitative evaluation of a digital density equalization technique in mammography ........................ 899 A.P. Stefanoyiannis, I. Gerogiannis, E. Efstathopoulos, S. Christofides, P.A. Kaplanis, A. Gouliamos

Interaction between charged membrane surfaces mediated by charged nanoparticles ................................................. 903 J. Pavlic, A. Iglic, V. Kralj-Iglic, K. Bohinc

Optical biopsy system for breast cancer diagnostics.......................................................................................................... 907 S.A.Belkov, G.G.Kochemasov, S.M.Kulikov, V.N.Novikov, U.Kasthuri, L.B. Da Silva

Implantable brain microcooler for the closed-loop system of epileptic seizure prevention ........................................... 911 I. Osorio, G. Kochemasov, V. Baranov, V. Eroshenko, T. Lyubynskaya, N. Gopalsami

Acetabular forces and contact stresses in active abduction rehabilitation ...................................................................... 915 H. Debevec, A. Kristan, B. Mavcic, M. Cimerman, M. Tonin, V. Kralj-Iglic, and M. Daniel

Time-Frequency behaviour of the a-wave of the human electroretinogram ................................................................... 919 R. Barraco, L. Bellomonte and M. Brai

Studies on the attenuating properties of various materials used for protection in radiotherapy and their effect of on the dose distribution in rotational therapy..................................................................................... 923 T. Ivanova, G. Malatara, K. Bliznakova, D. Kardamakis and N. Pallikarakis

Monte Carlo Radiotherapy Simulator: Applications and Feasibility Studies ................................................................. 928 K. Bliznakova, D. Soimu, Z. Bliznakov and N. Pallikarakis

Recovery of 0,1 Hz microvascular skin blood flow in dysautonomic diabetic (type 2) neuropathy by using Frequency Rhythmic Electrical Modulation System (FREMS) ........................................................................ 932 M. Bevilacqua, M. Barrella, R. Toscano, A. Evangelisti

Rehabilitation Engineering Complementary evaluation tool for clinical instrument in post-stroke rehabilitation ................................................... 936 I.Cikajlo, M.Rudolf, N.Goljar and Z.Matjacic

Electrically Elicited Stapedius Muscle Reflex in Cochlear Implant System fitting ........................................................ 940 A. Wasowski , T. Palko , A. Lorens , A. Walkowiak , A. Obrycka , H. Skarzynski

Use of rapid prototyping technology in comprehensive rehabilitation of a patient with congenital facial deformity or partial finger or hand amputation ........................................................................... 943 T. Maver, H. Burger, N. Ihan Hren, A. Zuzek, L. Butolin, and J. Weingartner

Using computer vision in a rehabilitation method of a human hand ............................................................................... 947 J. Katrasnik, M. Veber and P. Peer

Experimental Evaluation of Training Device for Upper Extremities Sensory-Motor Ability Augmentation .............. 950 J. Perdan, R. Kamnik, P. Obreza, T. Bajd and M. Munih

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New Experimental Results in Assessing and Rehabilitating the Upper Limb Function by Means of the Grip Force Tracking Method.................................................................................................................................... 954 M.S. Poboroniuc, R. Kamnik, S. Ciprian, Gh. Livint, D. Lucache and T. Bajd

The “IRIS Home” ................................................................................................................................................................. 958 A. Zupan, R. Cugelj, F. Hocevar

Evaluation of biofeedback of abdominal muscles during exercise in COPD................................................................... 961 M. Tomsic

Robotics and Haptics Can haptic interface be used for evaluating upper limb prosthesis in children and adults .......................................... 965 H. Burger, D. Brezovar, S. Kotnik, A Bardorfer and M. Munih

FreeForm modeling of spinal implants ............................................................................................................................... 969 R.I. Campbell, M. Lo Sapio and M. Martorelli

Grip force response in graphical and haptic virtual environment ................................................................................... 973 J. Podobnik and M. Munih

A Hierarchical SOM to Identify and Recognize Objects in Sequences of Stereo Images............................................... 977 Giovanni Bertolini, Stefano Ramat, Member IEEE

Assessment of hand kinematics and its control in dexterous manipulation..................................................................... 982 M. Veber, T. Bajd and M. Munih

A model arm for testing motor control theories on corrective movements during reaching ......................................... 986 D. Curone, F. Lunghi, G. Magenes and S. Ramat

Sports Sessions Acceleration driven adaptive filter to remove motion artifact from EMG recordings in Whole Body Vibration ..................................................................................................................................................... 990 A.Fratini, M. Cesarelli, P. Bifulco, A. La Gatta, M. Romano, G. Pasquariello

The Influence of Reduced Breathing During Incremental Bicycle Exercise on Some Ventilatory and Gas Exchange Parameters ............................................................................................................................................ 994 J. Kapus, A. Usaj, V. Kapus, B. Strumbelj

A Novel Testing Tool for Balance in Sports and Rehabilitation....................................................................................... 998 N. Sarabon, G. Omejec

Change of mean frequency of EMG signal during 100 meter maximal free style swimming ..................................... 1002 I. Stirn, T. Vizintin, V. Kapus, T. Jarmand V. Strojnik

Telemonitoring of the step detection: toward two investigations based on different wearable sensors? ................... 1006 G. Maccioni, V. Macellari and D. Giansanti

Repeatability of the Mean Power Frequency of the Endurance Level During Fatiguing Isometric Muscle Contractions ........................................................................................................... 1009 I. Stirn, T. Jarmand V. Strojnik

Ultrasound Image Processing Obtaining completely stable cellular neural network templates for ultrasound image segmentation ........................ 1013 M. Lenic, D. Zazula and B. Cigale

Segmentation of 3D Ovarian Ultrasound Volumes using Continuous Wavelet Transform......................................... 1017 B. Cigale and D. Zazula

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Selected Applications of Dynamic Radiation Force of Ultrasound in Biomedicine ...................................................... 1021 A. Alizad, J.F. Greenleaf, and M. Fatemi

Breast Ultrasound Images Classification Using Morphometric Parameters Ordered by Mutual Information......... 1025 A.V. Alvarenga, J.L.R. Macrini, W.C.A. Pereira, C.E. Pedreira and A.F.C. Infantosi

Virtual Reality in Medicine Development of Knee Control Training System Using Virtual Reality for Hemiplegic Patients and Feasibility Experiment with Normal Participants.................................................................................................... 1030 J.S. Park, J.H. Ku, K.W. Han, S.W. Cho,D.Y. Kim, I.Y. Kim, and S.I. Kim

Development of Alcohol craving induction and measurement system using virtual reality: Craving characteristics to social situation ........................................................................................................................ 1034 S.W. Cho, J.H. Ku, J.S. Park, K.W. Han, Y.K. Choi, K. NamKoong, Y.C. Jung, J.J. Kim, I.Y. Kim, and S.I. Kim

Cataract Surgery Simulator for Medical Education ....................................................................................................... 1038 R. Barea, L. Boquete, J. F. Pérez, M. A. Dapena, P. Ramos, M. A. Hidalgo

Special Sessions and Symposiums Clinical Engineering and Patient Safety Patient safety - a challenge for clinical engineering ......................................................................................................... 1043 J.H. Nagel and M. Nagel

MIDS-project – a National Approach to Increase Patient Safety through Improved Use of Medical Information Data Systems.................................................................................................................................................. 1047 H. Terio

Improving Patient Safety Through Clinical Alarms Management ................................................................................ 1051 Y. David, J. Tobey Clark, J. Ott, T. Bauld, B. Patail, I. Gieras, M. Shepherd, S. Miodownik, J. Heyman, O. Keil, A. Lipschultz, B. Hyndman, W. Hyman, J. Keller, M. Baretich, W. Morse and D. Dickey

A Clinical Engineering Initiative within the Irish Healthcare System toward a Safer Patient Environment ............ 1055 P.J.C. Pentony, J. Mahady and R. Kinsella

A Pervasive Computing Approach in Medical Emergency Environments.................................................................... 1058 J. Thierry, C. Hafnerand S. Grasser

System for Tracing of blood transfusions and RFID ....................................................................................................... 1062 P. Di Giacomoand L. Bocchi

A preliminary setup model and protocol for checking electromagnetic interference between pacemakers and RFID (Radio Frequency IDentification).................................................................................................................... 1066 R. Tranfaglia, M. Bracale, A. Pone, L. Argenziano , L. Pecchia

Current Status of Clinical Engineering, Health Care Engineering and Health Care Technology Assessment in Austria ............................................................................................................................................................................. 1070 H. Gilly

Clinical Engineering Training Program in Emerging Countries Example from Albania ........................................... 1074 H. Terio

BME Education at the University of Trieste: the Higher Education in Clinical Engineering ..................................... 1077 P. Inchingolo and F. Vatta

Certification of Biomedical Engineering Technicians and Clinical Engineers: Important or Not.............................. 1081 James O. Wear, PhD, CCE, CHSP, FASHE, FAIMBE

Content

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Findings of the Worldwide Clinical Engineering Survey conducted by the Clinical Engineering Division of the International Federation for Medicine and Biological Engineering .................................................................... 1085 S.J. Calil, L.N. Nascimentoand F.R. Painter

Clinical Engineering in Malaysia – A Case Study............................................................................................................ 1089 Azman Hamid

Medical Equipment Inventorying and Installation of a Web-based Management System – Pilot Application in the Periphery of Crete, Greece ..................................................................................................... 1092 Z.B. Bliznakov, P.G. Malataras and N.E. Pallikarakis

A prototype device for thermo-hygrometric assessment of neonatal incubators .......................................................... 1096 P. Bifulco, M. Romano, A. Fratini, G. Pasquariello, and M. Cesarelli

Health Technology Assessment in Croatian Healthcare System .................................................................................... 1100 P. Milicic

A QFD-based approach to quality measurement in health care..................................................................................... 1102 F. Dori, E. Iadanza and D. Bottacci, S. Mattei

EVICAB - European Virtual Campus for Biomedical Engineering The E-HECE e-Learning Experience in BME Education............................................................................................... 1107 P. Inchingolo, F. Londero and F. Vatta

Web-based Supporting Material for Biomedical Engineering Education ..................................................................... 1111 K. Lindroos, J. Malmivuo, J. Nousiainen

European Virtual Campus for Biomedical Engineering EVICAB................................................................................. 1115 J.A. Malmivuo and J.O. Nousiainen

BIOMEDEA ........................................................................................................................................................................ 1118 Joachim H. Nagel

Biomedical Engineering Education, Virtual Campuses and the Bologna Process ........................................................ 1122 E.G. Salerud and Michail Ilias

How New and Evolving Biomedical Engineering Programs Benefit from EVICAB project....................................... 1126 A. Lukosevicius, V. Marozas

Learning Managements System as a Basis for Virtual Campus Project ....................................................................... 1130 K.V. Lindroos, M. Rajalakso and T. Väliharju

Future of Medical and Biological Engineering Computer Aided Surgery in The 21 Century ................................................................................................................... 1132 T. Dohi, K. Matsumiya and K. Masamune

Multi-dimensional fluorescence imaging .......................................................................................................................... 1134 P.M.W. French

Nanomedicine: Developing Nanotechnology for Applications in Medicine ................................................................... 1135 Gang Bao

The Physiome Project: A View of Integrative Biological Function ................................................................................ 1137 C.F. Dewey

Synthetic Biology – Engineering Biologically-based Devices and Systems .................................................................... 1138 R.I. Kitney

XXVIII

Content

Biomedical Engineering Clinical Innovations: Is the Past Prologue to the Future?..................................................... 1140 P. Citron

Innovations in Bioengineering Education for the 21 Century ........................................................................................ 1142 J.H. Linehan

Index Authors......................................................................................................................................1143 Index Subjects .....................................................................................................................................1149

Control for Therapeutic Functional Electrical Stimulation Dejan B. Popovic1,2, Mirjana B. Popovic1,2,3 1

Department of Health Science and Technology, SMI, Aalborg University 2 Faculty of Electrical Engineering, University of Belgrade 3 Center for Multidisciplinary Studies, University of Belgrade

Abstract— We suggest in this review paper that control of assistive systems for individuals with disability caused by injury or disease of central nervous system has to be approached with rather sophisticated methods that are capable to deal with high redundancy, nonlinearities, time variations, adaptation to the environment, and perturbations. The use of three levels that provide interaction with user, coordination of multi joint activity, and biological actuators is likely to be the solution for future electrical stimulation assistive systems. This is especially important for therapeutic assistive systems that must mimic life-like movement. The top control level needs to be discrete and secure the recognition of intended movement and possibly some kind of feedback, the middle control level needs to be discrete and provide multi joint coordination that is based on temporal and spatial synergistic model of the movement. The lowest control level needs to be model-based in order to match the specifics of the musculo-skeletal system. The hierarchical hybrid control is inherently predictive adaptive controller that, if properly designed, could results with effective generation of segment movements that lead to life like function (e.g., walking, standing, manipulation, grasping, etc.). Keywords— Hierarchical hybrid control, Electrical stimulation, Rule-based control, Model-based control.

I. INTRODUCTION Several clinical trials demonstrated that intensive taskoriented exercise augmented with an assistive system based on electrical stimulation promotes recovery of sensorymotor functions in individuals after central nervous system injury or disease [1,2]. The reasons most likely contributing to the recovery are: 1) assistive system contributes to nearnatural activity of the paretic extremity; thereby, play a part in the re-development of healthy-like movement. 2) proprioception and exteroception are enhanced due to artificially induced movement, 3) the electrical stimulation activates afferent pathways in parallel with activation of efferent pathways, 4) ability to perform function increases the motivation to use the paretic/paralyzed sensory-motor mechanisms, and 5) voluntary exercise prevents disuse and development of compensatory strategies. The physiological explanation of the recovery is that the central nervous system plasticity is augmented during the said therapy. Studies using Positron Emission Tomography

(PET), functional Magnetic Resonance Imaging (fMRI), transcranial magnetic stimulation (TMS), and magneto encephalography (MEG) support the concept of functional reorganization after CNS lesions [3,4]. II. CONTROL METHODS FOR THE THERAPEUTIC FUNCTIONAL ELECTRICAL STIMULATION

We start with the target of this research; that is, a model of biological control that needs to be mimicked (Fig. 1). Electrical stimulation activates muscles with bursts of pulses (electrical charge) delivered via electrodes exciting the intact peripheral nerves, which subsequently leads to generation of action potentials that propagate in both afferent and afferent pathways. The direct response of the stimulation will be the contraction producing joint torques, ultimately leading to movement; yet, a reflex component of movement will follow due to excitation of afferent pathways. One method to control the bursts of pulses is to apply model-based open-loop method. There is no correction that could be applied to the electrical stimulation in case of deviation of the produced movement from the desired one. The open-loop control performance was found unsatisfactory due to several reasons: parameter variation, inherent time-variance, time-delay, and strong nonlinearities in the musculo-skeletal system. The engineering method to deal with these problems is to introduce feedback, that is, to correct for errors by using sensory information that assesses the deviations of the trajectory from the desired one. The error-driven control ensures better tracking performance and smaller sensitivity to modeling errors, parameter variations, and external disturbances. There are many theoretical studies and some simple applications of closed-loop control system in FES; yet, none

Fig. 1: Model of control of movement in a human

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Dejan B. Popovic, Mirjana B. Popovic

has reached the maturity and found use in rehabilitation. The main problem is that the model of the system is far from reality, and that the parameters of the system can not be determined with necessary accuracy. The alternative method for control was suggested by Tomovic and McGhee [5] in form of a finite state control of multi-legged locomotion. This control method evaluated into the black box model, termed Rule Base Control (RBC), where the structure of the system was not considered; yet, only the inputs and outputs. The RBC is an open-loop control driven by sensory information that switches from rule to rule that had been developed through heuristics. The RRC in its nature is on-off control, meaning that it does not consider the dynamics of the system. Rules for RRC are derived by using computerized classification, typically some kind of artificial neural network. Artificial neural networks have been incorporated into the control schemes as they are able to learn complex nonlinear mappings [6, 7]. The stability issues remain unresolved due to the black-box structure. The development of this control method led to the development of hierarchical hybrid control (HHC) that in principle could lead to better performance [8]. The expanded schema of the model in Fig. 1 shows the elements that HHC is integrating (Fig. 2). III. HIERARCHICAL HYBRID CONTROL OF MOVEMENT Hybrid means, in general, heterogeneous in nature or composition. The term "hybrid systems" is understood to describe systems with behavior defined by entities or processes of distinct characteristics. The hybrid systems of interest here are dynamic systems where the behavior is determined by interacting continuous and discrete dynamics. These systems typically contain variables or signals that take values from a continuous set (e.g., the set of real numbers) and also variables that take values from a discrete and typically finite set (e.g., the set of symbols {a, b, c}). These continuous or discrete-valued variables or signals depend on independent variables such as time, which also may be continuous or discrete; some of the variables may also be a

Fig. 2: The organization of sensory-motor systems leading to movement.

discrete-event that is driven in an asynchronous manner. There are several reasons for using hybrid models to represent movement. Reducing the complexity was and still is an important reason for dealing with hybrid systems. This is accomplished in hybrid systems by incorporating models of dynamic processes at different levels of abstraction. For another example, in order to avoid dealing directly with a set of nonlinear equations, one may choose to work with sets of simpler equations (e.g., linear) and switch among these simpler models. This is a rather common approach in modeling physical phenomena. In control, switching among simple dynamical systems has been used successfully in practice for many decades. The hybrid control systems typically arise from the interaction of discrete planning algorithms and continuous processes, and, as such, they provide the basic framework and methodology for the analysis and synthesis of autonomous and intelligent systems, i.e., planning to move the hand and grasp an object. The hybrid control systems contain two distinct types of components, subsystems with continuous dynamics and subsystems with discrete-event dynamics that interact with each other. Another important way in which hybrid systems arise is from the hierarchical organization of complex control systems. In these systems, a hierarchical organization helps manage the complexity, and higher levels in the hierarchy require less detailed models (discrete abstractions) of the functioning of the lower levels, necessitating the interaction of discrete and continuous components. There are analogies between certain current approaches to hybrid control and digital control system methodologies. In digital control, one could carry the control design in the continuous-time domain, then approximate or emulate the controller by way of a discrete controller and implement it using an interface consisting of a sample and a hold device. Alternatively, one could first obtain a discrete model of the

Fig. 3: The model of life-like movement controller

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Control for Therapeutic Functional Electrical Stimulation

Fig. 4: The organization of a man made HHC for restoring movement plant taken together with the interface and then carry the controller design in the discrete domain. In hybrid systems, in a manner analogous to the latter case, one may obtain a discrete-event model of the plant together with the interface using automata or Petri nets. The schema of an HHC based controller for movement incorporates three levels (Fig. 3). The top artificial control structure is the interface between the user and the machine. This interface is the principal command channel, and it allows the user to trigger the operation of their choice volitionally. The actual organization of the controller is sketched in Fig. 4. The interface initiates the activity of a discrete, rule-base controller. This rule-base controller operates as a discrete, sample data feedback control, and its main role is to distribute the commands to the lowest actuator levels. The rulebase controller is implementing the finite-state model of movement, and the rules have to be determined with sufficient generality to allow the application over many assistive systems to be applicable to the entire population with a similar level of disability. The rule-based control (RBC) system is applicable for the coordination level of control (Fig. 5). This level deals with the following: 1) the strategy of how to employ the resources available, and 2) the methodology of how to maximize the efficiency of the resources. The RBC in this multilevel control uses the simulation of movement as the pattern that has to be followed. The RBC considers that the system is to be applied in individuals with disability; hence, the heuristics is applied to the output of simulation of optimal control applied to the model customized with parameters that reflect the level of impairment of the potential user and healthy-like tra-

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Fig. 5: The schema of a rule-based control for coordination level of hierarchical hybrid controller.

jectories [9]. The RBC comprises the following elements: the “regular” rules that are sequentially switching from one to the expected action based on sensory input; “mode” rules that are responsible for selecting the appropriate set of regular rules; and “hazard” rules that deal with conflict situations. The conflict situations occur due to the uncertainty of the available sensory information and/or hardware limitations, in addition to unexpected gait events. The hazard rules result in the safety “behavior”, which attempts to minimize the eventual catastrophic consequences of the hazard (e.g., falling, obstacles, non-physiological loading). The lower, actuator control level is responsible for executing decisions from the coordination level. The actuator level deals with specific muscle groups responsible for the flexion or the extension of a single joint, or in other cases, the action of several joints when a multiarticular muscle is externally stimulated. The actuator level implements the continuous feedback control and structural modeling. IV. DISCUSSION Compared with other classes of dynamical systems, the sensory-motor systems supporting the execution of functional motions in humans have three unique features: 1) they are highly redundant; 2) they are organized in a hierarchical structure, yet with many parallel channels; and 3) they are self-organized relying, among other things, on an extremely complex connectionism. In spite of the above complexity, the movements resulting from the action of sensory system, as a rule, are deterministic and they follow the preferred way of performing the intended motor task.

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The technology has spawned many different types of control system; each suited to a particular application. Over a much larger time scale, the biological organisms have evolved control systems to suit many of species and physiological functions. The two streams of development have converged in the area of motor control rehabilitation. This paper proposes the integration of these two control issues. In rehabilitation of movements the aim is to activate joints in a controlled way so as to restore as much motor function as possible in humans with motor disabilities. The control strategies implemented in most of rehabilitation devices have so far been fairly simple, and have been developed largely in relation to the design of machines rather than to the design of nervous systems. Recent neurophysiological data show that some of these strategies have converged, so as to be quite similar to those in analogous natural systems. The question now is, how general is this outcome? In artificial devices, should we always strive to mimic the relevant natural control system on the assumption that it has been optimized in the course of evolution, and could we always mimic nature, given that our abilities to reproduce components of the neuromuscular system are limited? The presented control is of specific interest for neurorehabilitation, that is, a method allowing the preserved structures to find their best use if appropriately trained. The intensive, task -oriented exercise is showing very positive recovery in individuals with disability (e.g., non-ambulating subjects can walk unassisted for some distances). Neural engineering is where the ultimate successes at this stage must come. The development of new sophisticated; yet, simple to use devices that interface the central and peripheral nervous system opens new horizons in rehabilitation. The recent MEMS based technology makes dramatic impact to the development of rehabilitation technology. This technology provides today sensing and actuation that has been difficult to imagine only months ago. The computer power rises fast, and allows the processing and communication at levels that are appropriate for the use in various implantable systems. The development of power sources is still somewhat limiting factor for implantable systems. The intelligent control that resembles to natural control is the major missing link being essential for full integration of the

Dejan B. Popovic, Mirjana B. Popovic

technology and life-sciences knowledge into viable, effective rehabilitation systems.

ACKNOWLEDGMENT Danish National Research Foundation, Copenhagen, Denmark, and Ministry for Science and Environmental Protection, Belgrade, Serbia partly supported this work.

REFERENCES 1.

2. 3. 4.

5. 6. 7. 8. 9.

Yan TB, Hui-Chan CWY, and Li LSW. (2005) Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke - A randomized placebo-controlled trial, Stroke 36(1):80-5. Popovic MB, Popovic DB, Sinkjaer T, Stefanovic A and Schwirtlich L. (2003) Clinical Evaluation of Functional Electrical Therapy in Acute Hemiplegic Subjects. J Rehabil Res Dev 40(5):443-45 Khaslavskaya S and Sinkjær T. (2005) Motor cortex excitability following repetitive electrical stimulation of the common peroneal nerve depends on the voluntary drive. Exp Brain Res 162(4): 497-502 Ridding MC, Brouwer B, Miles TS, Pitcher JB, and Thompson PD. (2000) Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects. Exp Brain Res 131(1):135-43 Tomovic R. and McGhee RB. (1968) A finite state approach to the synthesis of bioengineering control systems. IEEE Trans Human Factors Eng HFE-7:65-69 Kawato M, Furukawa K, and Suzuki R. (1987) A Hierarchical Neural-Network Model for Control and Learning of Voluntary Movement. Biol Cybern 57:169-185 Kawato M. (1990) Feedback-Error-Learning Neural Network for Supervised Motor Learning. Advanced Neural Computers, pp 365-372 Popovic MB. (2003) Control of Neural Prostheses for Grasping and Reaching. Med Eng Phys 25(1):41-50 Popovic DB. (2003) Control of Walking in Humans with Impact to Standing and Walking, J Aut Control, 13:1-34 Author: Dejan B. Popovic Institute: SMI, Aalborg University, Denmark (also University of Belgrade, Faculty of Electrical Engineering, Belgrade, Serbia) Street: Fredrik Bajers Vej 7D3 City: 9220 Aalborg Country: Denmark Email: [email protected]

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EMITEL – an e-Encyclopedia for Medical Imaging Technology S. Tabakov, C. A. Lewis, A. Cvetkov, M. Stoeva, EMITEL Consortium King’s College London, Dept. Medical Engineering and Physics, UK and EMITEL Consortium – www.emerald2.eu Abstract— The paper gives a brief explanation of a new International project EMITEL and its associated multilingual e-Dictionary. The project is developing the first web-based e-Encyclopedia in the profession. EMITEL will address the lifelong learning of a wide range of specialists and will be available free on Internet. The project advanced work-inprogress - the e-Dictionary is already functioning at www.emitdictionary.co.uk Keywords— Education and Training, e-Learning

I. INTRODUCTION Contemporary medicine is impossible without medical technology and medical imaging equipment is one of the most complex technologies of our time. Its effective and safe use requires well educated and trained work force Medical Physicists and Engineers. The field of medical imaging and related technologies develops rapidly. The last 20 years introduced revolutionary methods as Magnetic Resonance, Molecular Imaging, etc. All these enter quickly in healthcare and often limited information is available about new methods and respective technology. Previous projects, as EMERALD and EMIT, developed training materials (e-books and Image Databases) to address the initial training of young medical physicists. However most “mature” specialists (who already work in healthcare) do not have “the luxury” of free special training time to learn all these new methods and technologies. This places the “older” specialists in a disadvantaged position, as no suitable material is available for their timely lifelong education. The new project EMITEL aims to improve this situation by providing an Internet-based tool (Medical Imaging Technology e-Encyclopaedia for Lifelong Learning - EMITEL), which will allow flexible use of the limited time of these specialists to acquire knowledge about the newest developments in the field. The need of such material was discussed and assessed at the two International Conferences on Medical Physics/Engineering Education and Training (ICTP, Trieste, 1998, 2003) - described in the book ‘Towards a European Framework for Education and Training in Medical Physics and Biomedical Engineering’, IOS Press.

II. E-DICTIONARY The project was initiated some 5 years ago with an original multilingual Dictionary of Medical Imaging Technology Terms, which quickly grew to a full Medical Physics Dictionary cross-translating terms between each of its languages. Initially the e-Dictionary was CD-based and included English, French, German, Swedish and Italian. Later it was expanded with Spanish and Portuguese. The volume of the Dictionary is approx. 4000 terms (either a single word, e.g. dose, or combined words e.g. absorbed dose, or complex terms e.g. Linear dose-response curve, etc.). Through EMITEL the Dictionary was developed as a web-based tool. Also, it was further updated with Polish, Hungarian, Estonian, Lithuanian, Romanian and Turkish. The possibility to include and to search different alphabets allowed the Dictionary to further expand into Thai and another 5 languages, which are in preparation for inclusion during 2007. The original Search Engine of the Dictionary allows also partial word search and search of complex terms (i.e. a word anywhere in the term). One can see the advanced work in progress on the Dictionary at www.emitdictionary.co.uk where the interface of the web e-Dictionary is shown on Fig. 1. The EMITEL Consortium encourages contacts with all specialists who would like for their language to be included in the Dictionary, and also with colleagues who could suggest further omitted terms. III. EMITEL E-ENCYCLOPEDIA EMITEL task is to include explanatory articles to each of the 4000 terms. The articles will aim at MSc-level and above. Each article will include images, graphs, examples and other additional information. Typical size of an article is 150-300 words. The articles will be in English, but will be linked to the appropriate language in the Dictionary. The e-Encyclopedia will aim at more shorter articles, which will provide sufficient information for the term, together with related diagrams and practical figures. This departure from large topical articles will facilitate its Web use and multilingual term translation. At the moment the EMITEL Consortium includes 20+ specialists from King’s College London and King’s College

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Hospital, University of Lund and Lund University Hospital, University of Florence and AM Studio, Plovdiv. The Consortium includes also the IOMP (International Organisation for Medical Physics) as an international partner through which colleagues from other countries will be additionally included. After the end of the project the Web based eEncyclopedia EMITEL will be available free to all colleagues and IOMP will take care for its constant and quick future update.

S. Tabakov, C. A. Lewis, A. Cvetkov, M. Stoeva, EMITEL Consortium

IV. CONCLUSION The previous EU projects, carried out by the core of the present consortium, developed the world’s first structured training packages for young specialists in this field – EMERALD (focusing on X-ray, Nuclear Medicine and Radiotherapy) and EMIT (focusing on Ultrasound and Magnetic Resonance Imaging) [1]. These materials are now used in some 70 countries worldwide. As a result EMIT Consortium received the inaugural EU Award for Education – The Leonardo da Vinci Award (Maastricht, Dec. 2004). The new project EMITEL addresses the life long learning of a wider audience. It also includes Radiotherapy Physics, Radiation Protection and Hospital Safety terms, what makes it useful for various other healthcare specialists. Such product does not exist at the moment. In order to collect a wide feedback and include more colleagues into the project, EMITEL Consortium is organizing an International Conference of Experts during May 2008. Information on the development of the project can be found at its web site www.emerald2.eu. EMITEL builds another layer on the innovative developments of e-Learning in Medical Engineering and Physics, described in the Special Issue of the Journal of Medical Engineering and Physics. EMITEL Consortium [2] believes that this new web based tool will be a valuable contribution to the lifelong learning of many colleagues around the world and will help the development of the workforce in Medical Engineering and Physics.

ACKNOWLEDGMENT The authors express their gratitude to the EU Leonardo Programme and their own Institutions.

REFERENCES 1.

2.

Tabakov S, Roberts C., Jonsson B., Ljungberg M., Lewis C., Strand S., Lamm I., Milano F., Wirestam R., Simmons A., Deane C., Goss D., Aitken V., Noel A., Giraud J. (2005), Development of Educational Image Databases and e-books for Medical Physics Training, Journal Medical Engineering and Physics, Elsevier, vol.27, N.7, p 591-599. EMITEL Consortium members: S Tabakov, C A Lewis, C. Deane, D Goss, G Clarke, V Aitken, A. Simmons, S Keevil, J Coward, C. Deehan, P Smith, F Milano, S-E Strand, F. Stahlberg, B-A Jonsson, M Ljungberg, I-L Lamm, R. Wirestam, M. Almqvist, T Jonsson, A Cvetkov, M Stoeva Author: Dr Slavik Tabakov

Fig. 1 e-Dictionary interface (example from English-French Translation)

Institute: King’s College London, Dept. Medical Engineering and Physics Street: 124 Denmark Hill, London SE5 9RS,U.K. Email: [email protected]

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From Academy to Industry: Translational Research in Biophysics R. Cadossi, M.D1 1

Laboratory of Clinical Biophysics, IGEA, Carpi, Italy.

Abstract— The translation “from bench to bedside” of a scientific discovery, proof of principle or simple idea, that originated within academia, into a successful industrial product is a complex, long and costly process. Many factors need to be accounted for and careful planning and protection of intellectual property are essential to retain the value of the idea. This analysis, based on more than twenty-five years of experience in the biomedical field at IGEA, is presented to outline the different steps involved in such an endeavour. Critical factors defining the different phases, from initial evaluation of the idea to marketing and post-marketing monitoring, are described focusing on development processes. Keywords— Translational research, intellectual property, marketing, Cliniporator.

I. INTRODUCTION This analysis intends to illustrate how it is possible, starting from a scientific discovery, a proof of principle or a simple idea matured in the academic field, to successfully create and market an industrial product. Basis of such analysis is the hands-on experience gained by the IGEA company, that for over twenty-five years has been designing, manufacturing and marketing electromedical devices. The decision processes described below are used during the development of our products; as an example the focus will be on the experience collected for the development of Cliniporator. The Cliniporator project, conducted with the support of European Union research grants, has allowed IGEA to gather a large interdisciplinary international experience, teaching valuable lessons in what a translational research project entails. The phases that have been identified and explained below for an effective and optimized industrialization process are heavily influenced by the peculiarities of the medical field. New product development in the medical field is usually a long process that requires large and long term investments. Product validation and marketing follow rules that are specific to this area, further adding to the complexity of projects. Nevertheless, the steps described below can easily be adapted and put into effect for any field of industry.

II. INITIAL EVALUATION OF THE IDEA AND INTELLECTUAL PROPERTY PROTECTION

In the medical field, the value of an idea, and the reasons why one should develop such idea, reside in its ability to: a) improve the quality of care; b) reduce medical cost; c) simplify procedure; d) financial return and/or personal recognition. Thus, the suitability of an idea for industrial development should be evaluated on the basis of factors that involve different company departments: Finance Department, Marketing Department, R&D. The factors to be taken into consideration include: a) the originality and/or novelty of the idea; b) the innovative content of the final product with respect to those already on the market; c) results from market analysis; d) the price competitiveness of the final product with respect to products already on the market; e) the financial and human resources available in the company to support the project; f) the capacity to undertake the project on the basis of company know-how; g) the availability of human, material and logistic resources; h) analysis of the clinical validation process feasibility. Following this initial evaluation of the idea, steps should be taken to ensure adequate protection of intellectual property inherent in the idea and/or that will be developed during the project. Ways to protect intellectual properties are: a) follow the patent process b) correct use of Confidentiality Disclosure Agreement (CDA) and Nondisclosure Agreement (NDA). III. FEASIBILITY STUDY: DEFINITION OF A WORKABLE PROJECT

The R&D department undertakes the preliminary research activity to identify the state-of-the-art technological solutions available to develop the initial idea in an industrial context. This feasibility study, and where possible the presentation of an early prototype, allows the Marketing Department and the Finance Department to evaluate whether the workable project meets the initial idea and the purposes of the different company functions and therefore whether the industrial development of the idea is viable.

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 10–13, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

From Academy to Industry: Translational Research in Biophysics

To obtain an effective feasibility study the R&D should: a) control and integrate the initial project specifics (the initial idea); b) research technical and manufacturing solutions; c) present the workable project, using sketches, diagrams or physical prototypes; d) present an initial evaluation of the cost of the final product. If the project needs to be developed with out of house expertise (i.e. subcontractors), care should be taken as to have some type of patent protection in place. Once all these steps have been successfully completed, R&D department will obtain the approval by Finance department to prepare a design plan. At this time the Project Leader will be identified. IV. DESIGN PLAN The Project Leader studies the work program and plans what will be the workflow of the project using a planning document that defines: a) specifics of the project; b) precise description of the tasks to be completed, and their assignment to appropriate workgroups c) the time plan for each task; d predefined control points to verify that the solutions developed are correct and compatible with the specifics of the design; e) the resources for the development of the project, as approved and made available by the Finance department; f) a contingency plan. Of note is the importance of good communication and coordination among different units participating in the program, be as they may different division within the same company or completely separate entities such as: other companies, research centers or hospitals. Such a condition will facilitate problem solving and drastically decrease delays due to miscommunication. V. VALIDATION OF A WORKING PROTOTYPE The Project Leader oversees and coordinates the workgroups involved in the programmed phases to obtain a working prototype, respecting the scheduled time frames and check points. As the project progresses the prototype will be subjected to functionality tests of the technology that is been developed. Specifically for electro-medical devices the prototypes will also be used to carry out scientific research that should include: in vitro and in vivo studies to characterize the mechanisms of action. In vivo study will also be a relevant part of the pre-clinical validation of the

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project. Final clinical validation of the device will be attained through clinical trials. VI. CLINICAL VALIDATION The Project Leader co-ordinates the scientific research necessary for the clinical validation of the developed technology. At this time it is extremely important to define the expected results and the parameters on the bases of which the efficacy of the treatment will be assessed. In the event of a negative outcome, one should consider either varying the specifics of the project or closing it down to limit financial and time losses. Provided the result of the clinical trial are positive, the technology cost/benefit ratio will be considered and compared to that of already existing alternative treatments to further assess viability and profitability of the project as a whole. VII. APPROVAL OF THE PROTOTYPE The Finance and Marketing Department and R&D evaluate the prototype whose technology has been positively tested and recognized as clinically valid. Indeed, it is necessary to select the characteristics to be included in the product, that should be manufactured and marketed. Finally, those specifications that have not yet been discussed should be defined, i.e. user interface, subsidiary functions and aesthetics. To carry out this evaluation the following are analyzed: a) features of the prototype; b) results of the functionality tests or of the scientific research; c) any new requirements identified by marketing; d) proposals for boxes, accessories and user interface; e) requisites for manufacturing. In this phase, considerations about localization of the product, such as interface language and cultural differences that could influence product acceptance and diffusion, are identified and implemented in the project. Once the prototype and the new additional specifics are approved, the development and marketing activity of the new product can be initiated. VIII. PREPARATION OF THE MARKETING STRATEGY The attainment of a “working” prototype, or rather the awareness of the performance of the new product and its particularities with respect to the competition or market alternatives, allows the Marketing Department to put together a precise strategy aimed at introducing the new product on the market.

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R. Cadossi, M.D

The Marketing Plan should be studied together with the Finance department, which provides the necessary resources, and with the Sales Management. For an effective marketing activity, it is necessary to carefully define: a) the target, i.e. the indications for use and who should use the product; b) the communication, i.e. the message; the instruments: brochures, leaflets, congresses, round tables, training centers, newspapers; c) the opinion leaders; d) the competition, i.e. the analysis of the competition, the alternatives to the new product; e) the resources, i.e. the investment needed for promotion, training and/or integration with the Sales Force; f) the price strategy. IX. IDENTIFICATION OF THE DEFINITIVE CONSTRUCTION SOLUTIONS

The R&D department develops the prototype, introducing modifications and integration to fulfill specification changes as determined during initial testing, or identified by the Marketing Department and choosing construction solutions suitable for manufacturing and which meet all the standards that apply to the product in question. To be able to develop the definitive solutions, effective coordination is needed between those working on the hardware, the software, the user interface, those writing the manuals and the forms and those working on obtaining the certification of the product. This co-ordination is managed and guaranteed by the Project Leader, who approves the solutions identified and transfers them to the Marketing Department that is responsible for the design of a precise and effective promotional strategy. The Project Leader also guarantees that every variation requested or proposed with respect to the already approved prototype is freshly discussed and approved by the Marketing Management. The product that is obtained by the development activity must meet the specifics of the project plan, the requisites defined subsequently and the standards defined in the different markets. The product is presented to the Marketing and Sales Division that, on the basis of the promotional strategy worked out define the “supplementary” aspects that are needed before sales begin: refining of the interface (colors, signs, messages); design of the labeling and packaging; commercial name, appearance and contents of the illustrative material. The approval of the final prototype, together with the definition of all the aspects necessary for manufacturing, gives the go ahead for the construction products for sale.

X. CERTIFICATIONS ATTAINEMENT AND TRANSFER TO MANUFACTURING

The R&D department co-ordinates the activities for the development of the first-series models and therefore: a) completes the certification process, completes the Technical File, the Device Master Record (DMR), and the Risk Management File (RMF); b) prepares the registration reports required by the compulsory norms and by the company Quality System; c) transfers to manufacturing the necessary data for the management of the components; d) transfers to manufacturing the know-how and the operational methods for the construction, testing and management of the product; e) co-ordinates the tests on the first-series models, necessary for the validation of the design and manufacturing process. The attainment of the certification, the transfer into manufacturing and the successful completion of the tests on the first-series models signals the end of the planning process. XI.

MARKETING ACTIVITY AND SALES STRATEGY

The start of the marketing activity, i.e. the preparation of the market for the introduction of the new product, together with its final development, provide the Sales Force with all the tools to start the detailed promotion in the field (Leaflets, Price Lists, Communication, Opinion Leaders). The Sales Force should prepare, together with the Finance and Marketing Department, a Sales Plan which defines: a) the priorities; b) the resources to be allocated to each objective; c) the return expected from operations; d) the contingency plan. XII. DISSEMINATION The members of the Marketing division who followed the development and validation of the product and who took care of the promotional strategy, the Core Group, select and prepare the Opinion Leaders in the countries where the new product will be introduced. In this sense the International Marketing Division creates, instructs, provides resources and tools for the National Marketing Divisions that have their references in the local Opinion Leaders. XIII. CUSTOMER CARE After the product has been marketed, Customer Care records every type of complaint, request for assistance and

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From Academy to Industry: Translational Research in Biophysics

feedback from the client. This information is monitored to identify problems and to initiate corrective action or make improvements to the product. Such solutions may involve the R&D process (updating the product), the manufacturing process and/or the promotional strategy. Any change to product needs to be approved by the Marketing and Sale Department before it is implemented in Products for sale. XIV. CONCLUSIONS The development of a product to be used to treat patients, a biomedical device, is certainly a long and costly process that involves all strategic functions of a company from the very onset of the project. The target and the potential diffusion of the new product have to be clearly identified since the beginning of the process. Moreover, peculiar to the development of a medical device is a further variable: i.e. the clinical validation whose outcome cannot be controlled. In fact, despite in vitro and in vivo results may be satisfactory, they do not necessarily guarantee that they can be translated into an effective clinical application. For example the above project steps have been followed in the successful experience we had in the Cliniporator project. Nevertheless we should not forget that from early experimental data on electrochemotherapy, that envisioned its use in clinical

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practice, to the introduction into the market of a CE marked device validated through the ESOPE clinical trial, 15 years have elapsed.

REFERENCES 1. 2. 3. 4. 5.

IGEA Quality Manual, Chapter 7.3: ISO 9001:2000. Bonutti PM, Seyler TM, Marker DR, Plate JF, Mont MA. Inventing Orthopedics: From Basic Design To Working Product. AAOS Annual Meeting Scientific Exhibit, San Diego, USA. 2007. Mir LM, Orlowski S, Belehradek J Jr, Paoletti C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses: Eur J Cancer. 1991;27(1):68-72. Lebar AM, Sersa G, Kranjc S, Groselj A, Miklavcic D. Optimisation of pulse parameters in vitro for in vivo electrochemotherapy: Anticancer Res. 2002 May-Jun;22(3):1731-6. Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation: Cancer Treat Rev. 2003 Oct;29(5):371-87. Author: Ruggero Cadossi, M.D. Institute: Street: City: Country: Email:

Laboratory of Clinical Biophysics, IGEA Via Parmenide 10/A 41012 Carpi (MO) Italy [email protected]

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Information Technology Solutions for Diabetes management and prevention Current Challenges and Future Research directions R. Bellazzi1 1

Dipartimento di Informatica e Sistemistica, Universita di Pavia, Italy

Abstract— This paper presents a list of current and future challenges for Information technology in Diabetes Mellitus management. Three main research areas are identified: supporting patients, supporting health care providers, including specialists, GPs and case managers and finally supporting organizations and health care policy makers. The new technological advances in context awareness, user modelling, data mining and integrated information systems enable the design and implementation of new decision support strategies which may be effective in improving the management and prevention of chronic diseases in general and of Diabetes Mellitus in particular. Keywords— Diabetes Management, decision support, information and communication technologies

I. INTRODUCTION Diabetes Mellitus (DM), a major metabolic disease related with a reduced or impaired capability of the body to regulate the Blood Glucose Level, is now reaching worldwide epidemic proportions. The prevalence of DM for all age-groups was recently estimated to be 2.8% in 2000 and to reach 4.4% in 2030, so that the total number of people with DM, which is currently 171 million, is projected to raise to 366 million in 2030 [1]. The International Diabetes Federation estimates that the majority of patients is affected by type 2 Diabetes (DM-2), namely 85-95% of Diabetics, while about 0.09% of the population is affected by type 1 Diabetes (DM-1). Europe has the highest number of DM-1 patients (1.27 million) (http://www.idf.org). Given its epidemical proportion, it is not surprising that DM is having a strong impact on the health care system of western countries. DCCT and UKPDS studies [2,3] have shown that DM related complications, including cardiovascular diseases, can be delayed or prevented through a strict metabolic control. For this reason a number of guidelines and best-practice procedures have been defined to improve the delivery of care. Moreover, it has been recently demonstrated that DM2 can be delayed or prevented, too, by means of intensive interventions on diet, exercise or medication; such interventions have been also proved to be cost-effective [4]. The epidemiological dimension of DM-2 is forcing national health authorities to launch programs for the prevention,

early diagnosis and management of DM-2 based on informative campaigns targeted to citizens. There are however several problems in the implementation of such prevention and disease management programs, mainly related to a timely identification of citizens at risk of diabetes and cardiovascular diseases and then to the implementation of personalized life-style and clinical interventions. Nowadays it has become clear that the difficulties in achieving a satisfactory level in the delivery of health care to DM patients are not related to the availability of knowledge on the best diagnostic and therapeutic procedures, while they are system and organizational problems [5]. Over the last thirty years a strong interest has been given to the design and implementation of systems based on Information and Communication Technology (ICT) aimed at supporting the management of DM, mainly in the areas of Electronic patient records, Decision support systems and telemedicine [6-8]. In particular, diabetes care is probably one of the areas in which telemedicine, e-Health and Consumer-health solutions have been more widely tested [9-11]. The chronic nature of the disease and the need of patients empowerment for performing glucose self-monitoring and insulin delivery makes DM a “natural” context to test ICT as a mean for the provision of home care. Some of the proposed systems are now running large clinical trials, although very few of them became part of disease management programs, supporting multi-faceted interventions for patient care [10, 12]. In this paper we will describe some of the most important research areas which may enable the effective implementation of ICT solutions for DM and may thus provide very useful tools for improving the delivery of care. II. CHALLENGES AND RESEARCH ARCH DIRECTIONS FOR ICT IN DIABETES MANAGEMENT

A number of unparalleled opportunities are nowadays available to implement disease management and prevention programs based on the current advances of research in ICT: •

The availability of centralized electronic data repository on drug and specialized visit prescriptions and on the citizen hospital admissions and discharges. Such data

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Information Technology Solutions for Diabetes management and prevention Current Challenges and Future Research directions

• • •

are a crucial source of information to perform citizen stratification for DM and cardiovascular risk. The availability of new research results on DM risk assessment, coming from epidemiology and from genetics/genomics/proteomic research. The availability of new ICT solutions based on usercentered design, mobile communication and theory of behavior change. The improvement of research in the areas of context awareness and wearable systems.

Those advances enable the design of new ICT-based decision support systems in DM management devoted to support all the actors involved in DM management and prevention: patients, diabetologists, GPs and case managers, health care policy makers. A. Supporting patients Traditionally, decision support systems have been classified as visit-by-visit systems and day-by-day systems, the first being aimed at supporting physicians and the second to help DM patients in their self-management activities. The availability of telemedicine solutions have changed this kind of paradigm, potentially providing patients and physicians with the same kind of information about selfmonitoring, though with different roles and responsibilities. The majority of the past efforts have been devoted to the design of systems for insulin management. We believe that current research frontier is on the contrary related to the citizen and patient empowerment through user modeling and context awareness. In the area of user modeling, there has been a tremendous growth in diversity of ICT solutions for over the last two decades, with particular reference to lifestyle behavior change. These systems provide health behavior change information to citizens on the basis of a variety of health behavior theories [13,14], using different communication media, ranging from Web sites to computer telephony interfaces (CTI). From a clinical viewpoint they have been applied to a wide number of behaviors, including DM related ones, such as physical activity promotion, diet adherence, medication regimen adherence. Overall, these systems have been shown to be effective in a number of randomized clinical trials [15]. Recently, an interesting paper has been published by Ma and colleagues on the delivery of information and communication support to DM patient on the Internet [16]. The system is able to select patient-specific information, prioritizing diabetes learning topics and defining individualized agendas for patient-physician encounters on the basis of the so-called “Diabetes Information Profile” (DIP). The DIP is a model, i.e. a multi-faceted profile, of

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the user which is progressively updated on the basis of the clinical data and of the patient interaction with the system. The technology has been evaluated through a small clinical study, which showed its potential effectiveness in providing useful information to patients. Web interfaces can be also used to implement embodied conversational agents and relational agents. which are animated computer-based characters that emulate human faceto-face conversation [17,18]. Promising future directions also involve wearable computers, PDAs and mobile phones as platforms for health behavior change interventions [19]. Other solutions would be of interest in order to seamlessly integrate support into the users’ everyday lives and to initiate the interaction with the user, such as Short Message Service (SMS) or natural language interaction systems integrated within CTI. The availability of such technologies can help to better define the “context” in which the conversation between the user and the helper application occurs. By context we mean the “interrelated conditions in which something exists or occurs”, including anything known about the participants in the (potential) communication relationship. Therefore, context will regard not only all the user data and information collected during the dialog but also something related to the “presence concept”. The presence concept depicts availability to communicate but proposed extensions include elements to be derived from user activity, sensors or others. The knowledge about the user (user modeling) and the context (context awareness) in which the monitoring activity is carried on opens interesting research questions concerning the personalization and distribution of decision support interventions. B. Supporting specialists, GPs and case managers Several computer-based systems for Diabetes management have been proposed since the early eighties [20,21,22]. Many of the systems described in the literature have been primarily designed to manage DM-1 patients, in accordance to the “specialist-patient” model of health care; on the contrary, the current interests are directed towards the management of DM-2 within a “specialist-GP-patient” model. The current trend is to integrate guidelines and decision support systems as reminders within Electronic Patient Records (EPR) to support complex primary care interventions. The need of integrated solutions are advocated also by the substantial lack of clinical evidence that stand-alone guideline-augmented EPR may be effective in clinical practice [23]. As an interesting example of integrated system we can refer to the Diabetes Audit and Research in Tayside (DARTS), which is a validated population-based diabetes information system that collects data coming from different

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sources, including hospital admissions, diabetes clinical visits and diabetes medication. DARTS have been redesigned to overcome the problem of “inertia to change”, which is considered the main reason for the sporadic uptake and partial use of ICT-based systems. DARTS combines different technologies to allow for universal data collection, correlation, dissemination, guideline provision, guideline implementation and others. Currently DARTS is used in one thousand general practice clinic sites and fifty major hospital clinics, routinely managing a diabetic patient population of more than 160,000 patients [24]. Another relevant integrated ICT intervention is the IDEATel project, now funded for eight years since the year 2000. IDEATel is designed to provide a telemedicine service in both urban and rural economically disadvantaged areas within New York State. The project involved 1,500 patients, half of them being managed through a telemedicine intervention. Patients, GPs, case managers and specialists are connected by means of an Internet service; the telemedicine service is fully integrated with an health-care information system and is empowered by guideline based reminders and alerts. After the first year of implementation some improvements in the clinical outcomes have been observed, in particular regarding blood pressure and LDL [25]. Finally, an interesting research effort has been represented by the European Project M2DM: Multi-Access Services for Managing Diabetes Mellitus. The main goal of the project was to develop and test a Multi-Access service for managing all type of Diabetic patients. The basic concept is to collect data in a central database server that can be accessed through the Web, through the phone or through dedicated software for data downloading from the glucometers. The M2DM system comprised a Web access, a CTI service based on an Interactive Voice response system and a smartmodem located at home. The Web pages were optimized for different access modalities, including mobile devices. A distinguishing feature of M2DM is to exploit technology for managing the knowledge available to patients and physicians. To this end, the information flows is regulated by a scheduler, called Organizer that, on the basis of the knowledge on the health-care organization, it is able to automatically send e-mails and alerts as well as to commit activities to software agents, such as data analysis. Many decision support tools are integrated in the system, including casebased and rule-based reasoning, as well as modeling and simulation software. Four medical centers and more than 60 patients have been involved in a one-year randomized controlled evaluation, which showed promising clinical and evaluation results, although not statistically significant in all medical centers [11].

R. Bellazzi

C. Supporting health care policy makers Policy makers are now dealing with the problem of DM risk stratification, in order to plan for tailored life-style and disease management interventions. A large number of studies are available on the definition of DM risk calculators, based on simple data which can be collected in primary care visits, such as Age, BMI, waist circumference, antihypertensive drug treatment; those calculators are often coupled with cardiovascular risk calculators, to compute the overall health risk profile [26]. Furthermore, the investigation of insulin resistance has received considerable attention over the last twenty years, leading to quantitative indexes like the quantitative insulin-sensitivity check index (QUICKI) [27] and the so-called “minimal model” [28,29]. Moreover, in the last few years, research is actively working to find novel markers of Diabetes risk based on genetic patient profiling. Current studies are looking for genes associated with phenotypic traits of the metabolic syndrome [30]. Less attention have been devoted to the exploitation of the information coming from the patients’ administrative data [31] collected by health care system, such as hospital admissions and discharges, drug prescriptions, ambulatory visits. This challenge seems particularly relevant for policy markers who seldom rely on health care information systems integrated with clinical EPR for DM management. The exploitation of Data Mining techniques, and in particular of temporal Data mining tools, may lead to define temporal patterns associated with the disease diagnosis. Such patterns may highlight precedence relationships between physicians prescriptions and patients outcomes which may lead to properly stratify the available population [32]. Finally, health care decision makers have been recently provided with new tools for decision analysis based on the so-called DM modeling, i.e. mathematical models of the disease progression which can be used to simulate the effect of novel strategies on a large population of patients, and to take decisions formally evaluating projected costs and benefits of such strategies [33]. Up to now, there are no integrated tools for risk stratification and decision making able to integrate the available data sources, the current research results and the more recent modeling efforts in a comprehensive solution for identifying subjects who needs tailored interventions. Research and technical implementations are needed to improve the implementation of prevention programs. III. CONCLUSIONS The need of new kind of interventions for chronic care management is related to two concurrent factors, the increase of the number of elderly chronic patients and the

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Information Technology Solutions for Diabetes management and prevention Current Challenges and Future Research directions

difficulty to improve their clinical outcomes. The availability of integrated health care information system is enabling the implementation of novel disease management and prevention programs, heavily relying on communication between citizens and health care providers, Current research in ICT may provide suitable tools and instruments to increase the quality of such programs by empowering patients and by optimizing the required organizational efforts.

ACKNOWLEDGMENTS I acknowledge Dr. Timothy Bickmore and Toni Giorgino for their help in writing this review.

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3. 4.

5. 6. 7.

8.

9. 10. 11.

12.

13.

Wild s, Roglic G, Green a, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes care. 2004;27(5):1047-53 Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: "double diabetes" in the Diabetes Control and Complications Trial. Diabetes Care. 2007; 30(3):707-12. UKPDS 33, Lancet 1998;352:837-53 Herman W, et al. The Cost-Effectiveness of Lifestyle Modification or Metformin in Preventing Type 2 Diabetes in Adults with Impaired Glucose Tolerance, Annals of Internal Medicine. 2005; 142 (5): 323332. Glasgow RE, et al. Report of the health care delivery work group: behavioral research related to the establishment of a chronic disease model for diabetes care. Diabetes Care. 2001; 24(1):124-30. Cavan DA, et al. Preliminary experience of the DIAS computer model in providing insulin dose advice to patients with insulin dependent diabetes. Comput Methods Programs Biomed. 1998; 56(2):157-64. Hetlevik I, Holmen J, Kruger O, Kristensen P, Iversen H, Furuseth K. Implementing clinical guidelines in the treatment of diabetes mellitus in general practice. Int J Technol Assess Health Care. 2000; 16(1):210-27. Montani S, Bellazzi R, Portinale L, d'Annunzio G, Fiocchi S, Stefanelli M. Diabetic Patients Management Exploiting Case-Based Reasoning Techniques, Comput. Meth. and Progs. in Biomedicine 2000; 62: 205-218. Gomez EJ, Del Pozo F, Hernando E. Telemedicine for Diabetes care: the DIABTel approach. Medical Informatics, 1996; 21:283-295 Starren J, et al. Columbia University's Informatics for Diabetes Education and Telemedicine (IDEATel) project: technical implementation. J. Am Med Inform Assoc. 2002; 9(1):25-36. Larizza C, Bellazzi R, Stefanelli M, Ferrari P, De Cata P, Gazzaruso C, Fratino P, D'Annunzio G, Hernando E, Gomez EJ. The M2DM Project--the experience of two Italian clinical sites with clinical evaluation of a multi-access service for the management of diabetes mellitus patients. Methods Inf Med. 2006; 45(1):79-84. Sperl-Hillen J, O'Connor PJ, Carlson RR, Lawson TB, Halstenson C, Crowson T, Wuorenma J. Improving diabetes care in a large health care system: an enhanced primary care approach. Jt Comm J Qual Improv. 2000; 26(11):615-22. Prochaska, J., & Marcus, B. (1994). The Transtheoretical Model: Applications to Exercise. In R. Dishman (Ed.), Advances in Exercise Adherence (pp. 161-180).

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14. Glanz, K., Lewis, F., & Rimer, B. (1997). Health Behavior and Health Education: Theory, Research, and Practice. SF, CA: Jossey-Bass. 15. Owen, N., Fotheringham, M., & Marcus, B. (2002). Communication technology and health behavior change. In K. Glanz, B. Rimer, F. Lewis (Eds.), Health behavior and health education. SF, CA: JosseyBass. 16. Ma C, Warren J, Phillips P, Stanek J. Empowering patients with essential information and communication support in the context of diabetes. Int J Med Inform. 2006. 75(8):577-96. 17. Cassell, J., Sullivan, J., Prevost, S., & Churchill, E. (2000). Embodied Conversational Agents. Cambridge: MIT Press. 18. Bickmore, T. and Picard, R. (to appear) "Establishing and Maintaining Long-Term Human-Computer Relationships" ACM Transactions on Computer Human Interaction (ToCHI). 19. Koch S. Meeting the challenges--the role of medical informatics in an ageing society. Stud Health Technol Inform. 2006;124:25-31. 20. Lehmann ED, Deutsch T. Application of computers in Diabetes care – a review. Part I and II. Med Inform. 1995;20(4):281-329. 21. Lehmann ED, Deutsch T. Computer assisted diabetes care: a 6-year retrospective. Comput Methods Programs Biomed. 1996, 50(3):20930. 22. Dorr D, Bonner LM, Cohen AN, Shoai RS, Perrin R, Chaney E, Young AS. Informatics Systems to Promote Improved Care for Chronic Illness: A Literature Review. J Am Med Inform Assoc. 2007 14(2):156-163. 23. O'Connor PJ, Crain AL, Rush WA, Sperl-Hillen JM, Gutenkauf JJ, Duncan JE. Impact of an electronic medical record on diabetes quality of care. Ann Fam Med. 2005 3(4):300-6. 24. Leese G., Boyle D., Morris A. The Taysisde Diabetes Network. Diabetes Research and Clinical Practice, 2006, 74,S197-S199. 25. Shea S, et al, A randomized trial comparing telemedicine case management with usual care in older, ethnically diverse, medically underserved patients with diabetes mellitus. J Am Med Inform Assoc. 2006;1340-51. 26. Lindstrom J, Tuomilehto J, The Diabetes Risk Score. A practical tool to predict type 2 diabetes risk Diabetes Care 26: 725-731,2003. 27. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85: 2402-2410, 2000 28. Magni P, Sparacino G, Bellazzi R, Toffolo GM, Cobelli C. Insulin minimal model indexes and secretion: proper handling of uncertainty by a Bayesian approach. Ann Biomed Eng. 2004 32(7):1027-37. 29. Bergman R, Ider Y, Bowden C, Cobelli C: Quantitative estimation of insulin sensitivity. Am J Physiol 236: E667-E677, 1979 30. Sladek R, et al., . A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-5. 31. Kristensen JK, Sandbaek A, Lassen JF, Bro F, Lauritzen T. Use and validation of public data files for identification of the diabetic population in a Danish county. Dan Med Bull. 2001 Feb;48(1):33-7. 32. Bellazzi R, Larizza C, Magni P, Bellazzi R. Temporal data mining for the quality assessment of hemodialysis services. Artif Intell Med. 2005;34(1):25-39. 33. Herman W., Diabetes Modeling. Diabetes care, 2003; 26 (11): 3182 Author: Ricccardo Bellazzi Institute: Dipartimento di Informatica e Sistemistica, Universita di Pavia Street: via Ferrata 1 City: Pavia Country: Italy Email: [email protected]

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Patient-Cooperative Rehabilitation Robotics in Zurich Robert Riener1,2 1

Sensory-Motor Systems Laboratory, ETH Zurich, Switzerland Spinal Cord Injury Center, University Hospital Balgrist, Zurich, Switzerland

2

Abstract— This paper gives a short overview of new patientcooperative robotic approaches applied to the rehabilitation of gait and upper-extremity functions in patients with movement disorders. So-called patient-cooperative controllers take into account the patient’s intention and efforts rather than imposing any predefined movement. Audiovisual displays in combination with the robotic device can be used to present a virtual environment and let the patient perform different gait tasks and activities of daily living. Furthermore, the sensors implemented in the robots allow to measure and assess the patient performance and, thus, evaluate the therapy status. It is hypothesized that such patient-cooperative robotic approaches can improve patient motivation and the quality of the therapy compared to conventional approaches. Keywords— Rehabilitation Robotics, Gait Therapy, Treadmill Training, Arm Therapy, Patient-Cooperative

I. ROBOT-AIDED REHABILITATION Task-oriented repetitive movements can improve muscular strength and movement coordination in patients with impairments due to neurological or orthopaedic problems. A typical repetitive movement is the human gait. Treadmill training has been shown to improve gait and lower limb motor function in patients with locomotor disorders. Similarly, repetitive arm therapy is used for patients with paralysed upper extremities after stroke or SCI. Several studies prove that arm therapy has positive effects on the rehabilitation progress of stroke patients. It was observed that more and longer training sessions per week and longer total training periods have a positive effect on the motor function. The finding that the rehabilitation progress depends on the training intensity motivates the application of robot-aided therapy [1-5]. In contrast to manually assisted movement training, with automated, i.e. robot-assisted, gait and arm training the duration and number of training sessions can be increased, while reducing the efforts spent by the therapists per patient. Furthermore, the robot provides quantitative measures, thus, allowing the observation and evaluation of the rehabilitation process [1]. An example for a typical arm therapy robot is presented in Fig. 1.

II. PATIENT-RESPONSIVE CONTROL So-called “patient-responsive” strategies will recognize the patient’s movement intention and motor abilities in terms of muscular efforts and adapt the robotic assistance to the patient’s contribution. The best control strategy will do the same as a qualified human therapist – it will assist the patient’s movement only as much as needed. This will allow the patient to actively learn the spatiotemporal patterns of muscle activation associated with normal gait and arm/hand function. The term “patient-responsive” comprises the meanings of compliant, because the robot behaves soft and gentle and reacts to the patient’s muscular effort, adaptive, because the robot adapts to the patient’s motor abilities, and supportive, because the robot helps the patient and does not impose a predefined movement. It is assumed that patient-responsive strategies will maximize the therapeutic outcome. Among many different patient-responsive controllers developed so far [2] one of the most promising is a “pathcontroller”, where not the robot, but the patient is controlling the timing of the movements. The patient can move freely along a path corresponding to a physiological walking pattern, and is corrected by a surrounding force field when he/she deviates from the path. An additional

Fig. 1 The Zurich arm rehabilitation robot ARMin [3-5]

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Robert Riener

multi-modal (visual, acoustic, and haptic) displays allowing the patient to solve any virtual activity of daily living (ADL). These VR tasks can increase the motivation of the patients to participate. IV. ROBOT-AIDED PATIENT ASSESSMENT

Fig. 2 Lokomat equipped with a multimodal display comprised by a stereo projection system, a doubly surround sound system, a wind-generating fan, and the Lokomat providing haptic feedback. Virtual objects can be projected motivating the patient to lift the leg.

supportive force can assist the patient’s efforts as much as needed. The strategy can be adapted to the individual patient’s capabilities. III. BIOFEEDBACK AND VIRTUAL REALITY Optimal training effects during gait therapy depend on appropriate feedback about performance. For the patient, the quality of movement and extent of activity are significant measures of performance that are not easily assessed subjectively, particularly when there are also deficits in sensation, proprioception, and cognition. The robotic devices ARMin and Lokomat are instrumented with potentiometers and force transducers, and thus, are capable of providing online feedback about joint movement and joint moment production, respectively. The feedback values enable easy presentation by graphical, acoustical, or tactile displays to the patient motivating him/her to improve his/her gait pattern during the therapy. Special Virtual Reality (VR) techniques are being established allowing the patients to perform specific gait or reach-and-grasp tasks. For example with the Lokomat virtual obstacles can be displayed that must be crossed by the patient (Fig. 2). An acoustic display generates the step sound and other environmental sound sources. Hitting the obstacle can be seen, heard and felt by a 3D screen, surround sound system and a force displayed by the Lokomat, respectively. A fan produces a wind that increases its intensity with increasing gait speed. Similarly, with the ARMin system any virtual scenario can be generated by

Compared to manual treadmill therapy, there is a loss of physical interaction between therapist and patient with robotic gait retraining. Thus, it is difficult for the therapist to assess the patient’s contribution and to provide necessary feedback and instructions. The values recorded by the robot sensors can provide feedback not only to the patient but also to the therapist allowing him to evaluate the patient’s effort and assess the therapeutic progress. Important measures to be assessed are primary and secondary impairments originating from brain or spinal cord injuries including muscle weakness/strength, muscle tone/spasticity, active and passive joint range of motion etc. These measures provide important outcome indicators for the therapist in assessing functional improvement with any therapy. Performing each of these tests during every rehabilitation session would be time-consuming. However, implementation of tests that can measure these parameters could be achieved by appropriate instrumentation of robotic devices. The enhancement of the robotic trainers would be a viable approach because no additional acquisitions are required. For example, force transducers offer a means to evaluate muscle strength and voluntary force. Potentiometers offer a convenient method to extract joint range of motion information. Last but not least, imposing joint movements at different speeds and concomitant measurements from force transducers offer a possibility to evaluate passive joint stiffness as well as active and passive muscle properties. V. CONCLUSION The aim of patient-responsive control strategies is to consider voluntary efforts and exploit remaining natural control capabilities of the central nervous system after damage of brain or spinal cord. The force information is used to adapt the robotic assistance to the patient’s motor abilities enabling the patient to contribute as much as possible to the movement. At the same time, force and movement recordings can be displayed to the patient for biofeedback purposes and serve the therapist to evaluate the long term results of the movement therapy. The effects of the responsive strategies on the patient can be compared to the behavior of a qualified human therapist,

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Patient-Cooperative Rehabilitation Robotics in Zurich

who moves the patient’s limbs with some amount of compliance. It is expected that the above-mentioned patientcooperative strategies will stimulate active participation by the patient and maximize the therapeutic outcome in terms of reduced therapy duration and an improved gait quality. The high potential for future robot-aided treadmill training lies in the combination of robot-assisted training with robot-assisted assessment. Thus, only one device is required to do both training and assessment. No additional efforts of donning and doffing are necessary, because the patient can use the training device also for the assessment before, during or after the therapy. Furthermore, the instrumented robotic actuation makes training as well as assessment not only repeatable, but also recordable. This is an important prerequisite for intra- and inter-subject comparisons required to assist the therapist in the evaluation of the rehabilitation process. In summary, patient-cooperative rehabilitation robotics has a high potential to make future gait and arm therapy easier, more comfortable, and more efficient. However, broad clinical testing is still required to prove these assumptions.

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Union (Marie-Curie Project “MIMARS”) Bangerter-Rhyner-Foundation, Switzerland.

and

the

REFERENCES [1] Riener, R., Lünenburger, L., Colombo, G. (2006) Humancentered robotics applied to gait training and assessment, Journal of Rehabilitation Research & Development 43, pp. 679-694. [2] Riener, R., Lünenburger, L., Jezernik, S., Anderschitz, M., Colombo, G., Dietz, V. (2005) Cooperative subject-centered strategies for robot-aided treadmill training: first experimental results. IEEE Transactions on Neural Systems and Rehabilitation Engineering 13, p. 380-393. [3] Riener, R., Nef, T., Colombo, G. (2005) Robot-aided neurorehabilitation for the upper extremities. Medical & Biological Engineering & Computing 43, p. 2-10. [4] Mihelj, M., Nef, T., Riener, R. (2006) A novel paradigm for patient cooperative control of upper limb rehabilitation robots, Advanced Robotics, in press. [5] Nef, T., Mihelj, M., Colombo. G., Riener, R. (2006) ARMin – Robot for rehabilitation of the upper extremities. IEEE Int. Conference on Robotics and Automation, ICRA 2006, Orlando. p. 3152-3157.

ACKNOWLEDGEMENTS I thank my team of the Sensory-Motor Systems Lab, ETH and University Zurich, and the team of the SCI Center, Balgrist University Hospital for their contributions to this work. Special thanks go to Dr. Matjaz Mihelj who contributed major parts to the ARMin developments. This project was partially supported by the Swiss National Science Foundation NCCR Neuro (project 8), the European

Author: Institute: Street: City: Country: Email:

Robert Riener ETH Zürich SMS-Laboratory Tannenstrasse 1 TAN E 4 8092 Zürich Switzerland [email protected]

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Systemic Electroporation – Combining Electric Pulses with Bioactive Agents Eberhard Neumann Physical and Biophysical Chemistry, Faculty of Chemistry, University of Bielefeld, Bielefeld, Germany Abstract— In the year 2007, the documentation of the first functionally effective electrotransfer of naked DNA by electroporation, with stable gene expression, is 25 years old. This first functional electro-uptake has been preceded, in 1972, by the first documentation of controlled electrorelease of cellular components from bovine medullar chromaffin granules. - In the meantime, the electroporation field pulse techniques combined with the application of bioactive agents, have culminated in the new clinical disciplines of electrochemotherapy and electrogenetherapy. There are continuously ongoing efforts to improve the pulse protocols by optimizing equipment and cell biological strategies, relying heavily on the increasing knowledge on molecular-mechanistic details derived from the various electroporation data. - The digression here is restricted to a survey-like appreciation of the early functional electroporation data and their thermodynamic and mechanistic interpretation. We briefly touch the potential to explore systemic electroporation for the treatments of tissue, in particular, tumors. The goal is to provide tools in order to optimize systemic electroporation protocols and the design of electrode arrays for clinical use. Keywords— DNA electrotransfer, electrorelease, dipole rearrangements, systemic electroporation

I. INTRODUCTION The Medicon 2007 happens to be also the frame of the 25th anniversary of the first documentation of “The electric pulse method for the stable transformation of biological cells with naked gene DNA“, celebrating the first functionally effective electro-transfer of nonviral DNA by electroporation with stable gene expression in 1982 [1,2]. Complementary to electro-uptake, ten years earlier, in 1972, the electric pulse technique had been used to achieve the first non-destructive electro-release of cellular components like catecholamines, ATP and chromogranine proteins from isolated chromaffin granules of bovine adrenal medullae [3]. These initial physical chemical studies on the fieldcontrolled electroporative uptake and release of mole- cules have been recently valued in Nature Methods [4] as seminal for the various biotechnological and medical applications of what now may be called „Systemic Electroporation“, i.e., the application of voltage pulses combined with bioactive agents.

The recent developments of the techniques of systemic electroporation culminate in the new clinical disciplines of electro-chemotherapy and gene electrotherapy (L. Mir, R. Heller, D. Miklavcic, J. Teissie, G. Sersa, et al.). The following digression is restricted to a critical appreciation of the early data of functional electro-poration and the early molecular-mechanistic proposals for pore formation in high electric fields, along some of the original references (E. Neumann et al.). II. PORATION THERMODYNAMICS A. Electrochemical ansatz Already in 1982, a simple chemical scheme for the structural overall transition from a cascade of field sensitive closed membrane states (C) to the sequence of porous states (P) has been chemically formulated as: (C)

(P)

(1)

The overall distribution equilibrium constant of this overall scheme is specified as the state density ratio K= (P)/(C) = f/(1-f) and the fraction of pore states is f = (P)/[(P)+(C)]. It is found that both, K and f, increase with increasing field, maximally up to a few 0.1 percent in cells, and a few percent in curved lipid bilayers. A general analytical ansatz has been specified in terms of a generalized van t’ Hoff relationship, covering as a total differential, changes dT in temperature T in Kelvin units, changes dp in pressure p and changes dE in the strength E of the locally active electric field, relative to the molar energy unit RT, RT ⋅ d n K = (ΔH° / T) p,E dT − (ΔV° )T,E dp + ( ΔM°) p,T dE

(2)

Here R = k N A is the gas constant, k the Boltzmann constant and N A the Loschmidt-Avogadro constant. Note that Eq.(2) refers to three physical poration phenomena. Electroporation is characterized by the standard value ΔM 0 = M(P) - M(C) of the reaction dipole moment for the C to P transition, sono-poration by the standard reaction volume ΔV° and thermo-poration, including laser optoporation, by the standard reaction enthalpy ΔH° . Note that ΔH° is the total energy at constant pressure p, at a given

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Systemic Electroporation – Combining Electric Pulses with Bioactive Agents

temperature T and field strength E. Note that, for field effects, we have to specify the reaction enthalpy as ˆ + TΔS ΔH = ΔG

(3)

where the work potential ΔGˆ = ΔG − E ⋅ M is the Legendre-transformed Gibbs reaction energy, ΔG the ordinary reaction Gibbs energy in the field E, M the projection of the total electric moment vector M onto the direction of E, and ΔS the reaction entropy, all at constant outside pressure. It is worth mentioning that Eq. (3) reflects the first law of electro-thermodynamics at constant pressure in a canonical ensemble, i.e., a reactive system neighboured by other molecules. The electro-thermodynamic standard term ΔGˆ ° is the reversible extra work and T Δ S° refers to the reversible, i.e., exchangeable, heat energy. B. Chemical Electrothermodynamics The connection between the experimental signal (S) and the fractional effect f=S/ Smax and the electrothermodynamic quantities is via the relationships K = f/(1-f). The field dependence of K (and thus of the fraction f) is given by: K(E) = K(0) ⋅ exp X(E)

(4)

Eq. (4) reflects the electrochemical equilibrium condition ˆ = 0 , such that for dipolar molecular organizations ΔG ˆ ° results. The field effect factor is specified RT ⋅ n K = −ΔG as X(E loc ) =

∫ ΔM ⋅ dEloc RT

,

(5)

where E loc is the local field. If we refer to permanent dipoles, E loc is the directing field E dir , calculated from the induced field in given by: E m = - Δϕm /d m ,

(6)

where d m is the membrane of thickness d m , Δϕm the potential difference across the membrane. According to Maxwell, the electric current density vector for cross membrane cation and anion flows is given by. jm = σm (−∇ϕm ) = σm E m

(7)

where σ m is the membrane conductivity (of all the pores), The stationary value of the (Maxwell-Wagner) polarization-induced electric potential difference Δϕm (or Einduced membrane potential) for spherical membranes with the scalar value a of the radius vector r, under the angle θ to the direction of the homogeneous external field vector E, is given by:

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Δϕm (θ) = - (3/2) ⋅ a ⋅ E ⋅ f σ cosθ

(8)

applicable for the description of current flows, consistent with Eq. (7), through the two hemispheres of a spherical membrane shell. Integration within the boundaries θ = 0;π yields the average membrane potential: Δϕm = −

3 E⋅a ≈ − E⋅a , 2

(9)

as a practically useful approximation for isolated cells as well as for densely packed cells in cell pellets or tissue. The average membrane field amplification is then given by: Em ≈ E a / dm

(10)

For instance, the amplification factor of a sphere with radius a = 10 µm and d m = 10 nm is a/d m = 10−3 . Finally, substitutions into Eqs. (4) and (5) result in expressions which permit to determine the reaction dipole moment or the polarization volume (giving the pore radius). Substitution of the respective expressions for K = f /(1-f) yields the relationship for the field-induced fractional change, Δ f = f(E) - f(0), relative to the zero-field fluctuation term f(0) as: ⎛ K 0 exp X K0 Δf = ⎜ − 1 + K exp X 1 + K0 0 ⎝

⎞ K 0 (exp X − 1) ⎟= ⎠ (1 + K 0 exp X)

(11)

In the case that, at E = 0, the condition K 0 1 holds true, the second part of Eq. (11) is a very good approximation of the first part. Eq. (11) has been frequently used to determine reaction dipole moments and/or reaction volumes and thus average pore radii, independent of the selective assumption of a balance of electric free energy and line/surface tension energies. It is also important to note that the exponential time courses indicate that it is the number of defined pores of a given type, which increases with increasing field strength, and that the data do not indicate continuous pore expansion. C.Reaction couplings and normal modes

In practical work, it has turned out that the overall state (C) in scheme (1) represents a whole cascade of several steps ( C1 C2 ... ) and that also (P) must be replaced with ( P1 P2 ... ). The electro-thermodynamic analysis is then more complex, too. For instance, if the kinetic data are consistent with the state transition cascade C P1 P2 , the respective terms are: K1 = P1 / C and f1 = P1 /(P1 + C) , and K 2 = P2 / P1 and f 2 = P2 /(P1 + P2 ) , both steps associated with the re-

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Eberhard Neumann

spective separate reaction moments and polarization volumes. The single normal modes are characterized by the fielddependent normal mode relaxation times and amplitudes, yielding molecular polarization volume of each mode, and thus the respective pore radii and fractions of pores. The data on cells, isolated or in densely packed cell pellets, and on lipid vesicles, are consistent with at least two types of pores. The first type is a kind of perm-selective “NernstPlanck” pore, permitting transport either of cations or of anions, which thus go separately through different pores. So, on average, half of the pores transport cations and, parallel to it, the other half counter-transport anions. The transport of this type is a kind of ion exchange, e.g., cations go in on one hemisphere and go out on the other hemisphere such that there is no net transport of ions, for instance, out of the compartment. The data further suggest that these ion exchange pores (of radius r/nm =0.8 ± 0.2) can, at a higher pore density, develop larger pores at the expense of the smaller ones. The lager pores (r ≥ 1 nm) permit net transport of ions, for instance, net outflow from a cell of higher internal ion concentration than the outside. Further progress in the theory shows that the observation of field strength thresholds for measurable signals, as quantified in strength-duration curves, can be rationalized as a limit in the experimental detection (“visibility” threshold). The experimental threshold does certainly not just reflect the energetic balance of electric polarization and surface tension and (counter-acting) line tension. III. ELECTROPORATIVE TRANSPORT In essence, the field primarily acts on the structure, leading to pores of defined size. Concomitant transport is thus structurally controlled, the permeability changes both are based on the poration steps and resealing processes. Therefore the kinetics of electroporative transport also reflects the underlying structural changes, i.e., number and type of transport passages. Proper analysis provides, on the one hand permeability coefficients for the diffusion of molecules across concentration gradients. On the other hand, we obtain the kinetic parameters of the field-dependent pore formation and resealing processes. It is recalled that the mole flow (mol/s) of ion transport must be formulated in terms of the, recently introduced, concept of time-dependent transport coefficients. These coefficients explicitly reflect the, usually exponential, kinetics of poration processes and the flow coefficient of resealing indicates the much slower process of pore resealing. In

any case, the measured transport curves, like the time courses of conductance changes are therefore exponentials of exponentials. This can deceive smeared exponentials of the “Kohlrausch-type”. Specifically, the time courses reflect, in a folded form, the change in the fraction of pores, because the mole flow is proportional to the flow area, i.e., to the increasing or decreasing number of pores. Therefore, proper analysis starts with the mole flow, and not with the mole flow density (mol/s m²) or mole flux (=flow per area), in order to rationalize time-dependent flow coefficients. In addition, the value of the flow coefficient at the time point of the end of the applied pulse, yields the kinetic parameters for the rate limiting, (primary) structural transitions, preceding the (secondary) transport processes. IV. LOCAL LIPID REARRANGEMENTS

(PORES)

Molecular mechanistic, it had been presumed and explicitly indicated already in 1982 that the field forces cause lipid rearrangements such that the locally the charged groups and dipolar lipid head groups form a specific pore wall like that in hydrophilic or inverted pores. The dipolar head groups were drawn as aligned parallel to the external field direction [1]. This presumption has been recently supported by both, relaxation kinetic data obtained with small lipid bilayer vesicles, and by molecular dynamics simulations of the molecular rearrangements of lipid and water molecules involved in membrane electroporation. The technique of cell electroporation has been recently extended to ultra-short pulses with nominally very high external electric field strengths. At these high external field strengths and the short rise times, probably the rapid dielectric polarization of interfaces, besides the slower MaxwellWagner ionic polarization, may rapidly induce locally larger fields which, in turn, affect primarily the intracellular organelles. Ultra-electroporation is supposed to have powerful clinical potential, for instance, for inducing cell apoptosis in malignant tissue (K. Schoenbach, J.C. Weaver), Analytically, if the experimental electroporation times are expressed as a function of the respective directing field, (calculated from the external field using the dielectric constant of the polar environment), the entire field strength range, from moderate field strengths and short pulse times up to the very high external fields of the ultra-short pulses, can be consistently described with one and the same permanent dipole moment. The electro-thermodynamic analysis yields the mean dipole moment of 91.7 ( ± 5.0) 10-30Cm (27.4 ± 1.4 D) associated with the elementary unit, involved in a defined dipolar rotation process.

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Systemic Electroporation – Combining Electric Pulses with Bioactive Agents

If we compare this value with the dipole moment of the zwitterionic phosphatidylcholine head group of (70 ± 5)10-30 Cm (21 ± 2 D), we may conclude that the hydrated ionic and dipolar lipid head groups, where the water molecules in the asymmetric hydration shells of the ionic groups lead to higher dipole moments, are the molecular receptors for the interaction of the local field with the membranes. Further on, we quantify rotations of these dipolar field receptors into field-parallel positions in the walls of the hydrophilic (inverted) electropores, as one type of the dominant elementary processes in membrane electroporation. Besides the structural (C) = (P) model and the suggestion of direct field effects on the dipolar lipid head groups, the membrane electroporation processes have been viewed as a structural hysteresis with rapid in-field electric pore formation and much slower field-off resealing [5]. Since the late seventies pure physical theories have been developed and they continue to provide additional deeper insights (K. Kinosita, Jr., T.Y. Tsong, Y.A. Chiz-madzhev, J.C.Weaver) into physical details of. On the level of densely packed cells and tissue, conductivity data have been interpreted as models for tissue. For instance, field distributions across tissue between electrodes have been calculated (D. Miklavcic) and successfully applied for the design of new electrode arrays and medical electroporators. V. CONCLUSIONS In summary, the first functional electrotransfer of DNA in 1982, was the starting point of many fruitful studies, also aiming at the optimization of the guidelines of cell biological and clinical electroporation protocols and for the devel-

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opment of new electrode arrays and electro-porators such as the semi-automatic EU- Cliniporator©.

ACKNOWLEDGMENT We gratefully acknowledge financial support by the DFG, Bonn, grants Ne-227/1-9; by the ministry MSWF of the Land NRW for grant ELMINOS; by the European Union, Brussels, center grant QLK3-CT-1999-00484.

REFERENCES 1. 2. 3. 4. 5.

Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse lyoma cells by electro-poraton in high electric fields, EMBO J, 1, 841-845 Wong TK, Neumann E (1982) Electric field mediated gene transfer, Biophys Biochem Res Commun 107, 584-587 Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes, J Membr Biol 10, 279-290 and (1973) 14, 194-196 Eisenstein M (2006) A look back: a shock to the system, Nature Methods, 3, 66 Neumann E (1989) The relaxation hysteresis of membrane electroporation, In: Electroporation and electrofusion in cell biology. Eds. Neumann E, Sowers AE, and Jordan CA, Plenum Press, p.61-82 Author: Eberhard Neumann Institute: Physical and Biophysical Chemistry, Faculty of chemistry, University of Bielefeld Street: P.O. Box 100 131 City: Bielefeld Country: Germany Email: [email protected]

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An algorithm for classification of ambulatory ECG leads according to type of transient ischemic episodes A. Smrdel1 and F. Jager1 1

Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia

Abstract— We developed and evaluated an algorithm for classification of ECG leads in ambulatory records according to type of transient ischemic ST segment episodes using the LongTerm ST Database. The algorithm robustly generates ST level function in each ECG lead, tracks non-ischemic ST changes to construct the ST reference function and subtracts it from the ST level function to obtain the ST deviation function. Then the algorithm using statistical moment of the histogram of the ST deviation function given lead classifies the lead according to type of transient ischemic ST episodes (elevations, depressions). The algorithm correctly classified all 9 ECG leads with elevated and 89 out of 90 ECG leads with depressed transient ischemic ST episodes.

severe cases of ischemic heart disease, such as Prinzmetal's angina, while the depressed ischemic episodes appear in patients with milder cases of ischemic heart disease, such as stable angina. Furthermore, elevated ST segment indicates high risk of mortality [2], an ischemic injury [3], or an acute myocardial infarction [4]. As a diagnostic tool it would be beneficial to be able to determine the severeness of the heart disease by analyzing ambulatory ECG records and determining orientation of leads. In this paper we present an algorithm to classify ambulatory ECG leads according to their orientation. The algorithm was developed and evaluated using the LTST DB.

Keywords— Ambulatory electrocardiogram, transient ischemia, ECG lead classification, Long-Term ST Database.

I. INTRODUCTION Ischemia is one of the most common heart diseases. It is a state when there is insufficient supply of heart muscle with oxygenated blood. This can lead to myocardial infarction and, in worst case, death. In electrocardiogram (ECG), ischemia is manifested as change of ST segment morphology (ischemic ST segment changes). In addition, nonischemic changes of ST segment morphology are similar to true ischemic changes and include: heart-rate related ST segment changes, changes of ST segment level due to sudden shifts of the electrical axis of the heart (axis shifts) due to body position changes, and slow drifts of ST segment level due to diurnal changes or effects of medications. Ischemic changes and non-ischemic heart-rate related changes construct transient ischemic and transient heart-rate related ST segment episodes respectively. According to the shift of the ST segment level (positive or negative), the ST segment episodes are elevated or depressed. If we observe ambulatory ECG records, we notice, that majority of ECG leads contain only one type of episodes: elevations or depressions, while only a small number of leads contain both types. Therefore we can define the lead orientation such as: positive (only elevations present), negative (only depressions), mixed (elevations and depressions), and no orientation (no episodes). Elevated ischemic ST episodes, as we can observe in ambulatory ECG records of the Long-Term ST Database (LTST DB) [1], usually appear in patients with

II. MATERIAL AND METHODS The LTST DB includes 86 2- and 3-lead 24-hour ambulatory records (190 ECG leads), obtained during daily clinical practice. Each record contains reference annotations (set by human expert annotators) for ischemic and heart-rate related ST segment episodes, and human expert reference annotations that define time-varying ST segment reference level (non-ischemic path). By subtracting time-varying ST segment reference level from actual ST segment level the ST segment deviation level or the ST segment deviation function is obtained in which transient ischemic and heartrate related ST segment episodes are annotated. These ST segment episodes were annotated according to annotation criteria, which state that: • • •

an episode begins when the magnitude of the ST deviation function first exceeds 50 μV; the ST deviation function must reach a magnitude of Vmin or more throughout the interval of at least Tmin s; the episode ends when the ST deviation function becomes smaller than 50 μV, provided that it does not exceed 50 μV in the following 30 s.

Values for Vmin and Tmin differ according to three annotation protocols: • • •

Protocol A: Vmin = 75 μV; Tmin = 30 s; Protocol B: Vmin = 100 μV; Tmin = 30 s; Protocol C: Vmin = 100 μV; Tmin = 60 s; For this study we chose reference annotations according to protocol B. For each lead of each record of the LTST DB, we

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An algorithm for classification of ambulatory ECG leads according to type of transient ischemic episodes

visually verified the episodes in order to determine the lead orientation: if the extrema of all episodes in the lead were positive, the lead has positive orientation; if the extrema of all episodes were negative, the lead has negative orientation; if the episodes had negative and positive extrema the lead orientation is mixed; and if there were no episodes, the lead has no orientation. In our study we included leads with transient ischemic ST episodes only (104 leads), and leads without any ischemic or heart-rate related ST episodes (42 leads). Of the former, 9 have elevated episodes only, 90 have depressed episodes only, while 5 leads have elevated and depressed episodes. Leads which contain heart-rate related episodes or both types were excluded (44 leads). The algorithm developed for classification of leads according to their orientation is based on our previous work [5,6]. It is composed of following modules. A. Preprocessing The algorithm initially robustly preprocesses raw ECG data, and extracts noises and abnormal heart beats. To further avoid the effects of noise the average heart beats are constructed. Each normal heart beat in the raw ECG signal is replaced with the average heart beat. For the construction of each average heart beat that replaces individual current heart beat normal non-noisy heart beats in the 16 s neighborhood of the current heart beat are used. To construct the ST level function given lead, the algorithm first searches for the isoelectric levels and J points in each average heart beat. To determine the isoelectric level, I(j), where j denotes average heart beat number, the algorithm searches for the “flattest” part of the signal from the fiducial point, FP(j), backwards [5]. For the position of the J point, J(j), the algorithm searches forward from the FP(j) for a part of a waveform that “starts to flatten” [5]. After that, the ST segment amplitude is measured in each average heart beat and in each lead as the difference between the amplitudes at the point of measurements of ST segment level, J(j)+ 80 ms, and isoelectric level, I(j). These measurements constitute `fine' ST level function, s(i,j), where i denotes the lead number. This function is then resampled (ΔT=2 s) and smoothed to obtain the `raw' ST level function, s(i,k), where k denotes the sample number. Examples of the ST level function derived by the human expert annotators of the LTST DB and that derived by the algorithm are shown in Fig. 1.b and 1.d respectively. B. Tracking of slow drifts and detection of axis shifts Non-ischemic events have to be excluded from the ST level function. The algorithm tracks the non-ischemic path in the ST level function to create the ST reference function,

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which is then subtracted from the ST level function to obtain the ST deviation function. In the first step, slowly varying reference trend is tracked. The filters of 6 h 40 min ( h g ) and 5 min ( hl ) in duration are applied to obtain the timevarying global, rg (i, k ) , and local, rl (i, k ) , ST reference level trends respectively. Then the estimation of the reference level, r1 (i, k ) , which tracks slow drifts, but skips faster events and episodes is obtained using: ⎧⎪rg (i, k ) : if rg (i, k ) − rl (i, k ) > 50 μV r1 (i, k ) = ⎨ ⎪⎩rl (i, k ) : otherwise.

(1)

In the second step, axis shifts due to body position changes are detected. To detect step changes of the ST level function the ST level function and the Mahalanobis distance functions of the first order of the QRS complex and ST segment Karhunen-Loève (KL) coefficient feature vectors are used. Axis shifts are detected in all three functions as a step change which has a flat interval before and after the step change. In each of the three functions, the algorithm first searches for a flat interval of T f =216 s in length, which has to have its mean absolute deviation from its own mean less than K f =20μV for the ST level function, and less than Σ F =0.33 SD (SD - standard deviation) for both Mahalanobis distance functions of the first order. This has to be followed by a step change, characterized by the moving average value over Ta =72 s in length, and has to change for at least K S =50 μV for the ST level function and for at least Θ QRS =0.5 SD for the QRS KL distance function and for at least Θ ST =0.4 SD for the ST KL distance function in the next 2Ta =144 s in length. This step change has to be followed by another flat interval in all three functions defined the same as for the first flat interval. In the intervals surrounding the step change, the ST reference function is updated, following: ⎧r1 (i, k ) : if rg (i, k ) − s (i, k ) < 50μV ∧ ⎪⎪ r2 (i, k ) = ⎨ rl (i, k ) − s(i, k ) < 50μV ⎪ s (i, k ) : otherwise. ⎪⎩

(2)

It means that those parts of the ST reference function coinciding with sudden step changes are replaced by the ST level function. By subtracting the ST reference function of the lead from the ST level function the ST deviation function, d(i,k), is finally constructed: d (i, k ) = s(i, k ) − r2 (i, k ).

(3)

An example of an ST deviation function is shown in Fig. 1.f, that resembles one constructed by the human experts (Fig. 1.c).

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A. Smrdel and F. Jager

Fig. 1 Time trends of a three-lead record s30661 (shown is the first lead) from the LTST DB (6 hour excerpt from 24 hour record is shown, starting at 10 hours after the start of the recording). Legend: (a) heart rate ([bpm]); (b) ST level function as derived by the annotators of the LTST DB ([μV]); (c) ST deviation function as derived by the annotators ([μV]); (d) ST level function as derived by the algorithm ([μV]); (e) ST reference function as derived by the algorithm ([μV]); (f) ST deviation function as derived by the algorithm ([μV]); (g) an axis shift as detected by the algorithm (a vertical tic above the line), and two ST segment episodes and two axis shifts (vertical tics below the line) as annotated by the expert annotators. Determination of lead orientation To determine the lead orientation, the samples of the ST deviation function of an ECG lead, d(i,k), are considered as samples of a random variable to construct a histogram of this function. An example of such a histogram of the first lead of record s30661 is shown in Fig. 2. Next, the z-th statistical moment above the threshold K S =50 μV: B z 1 (4) mz+ (i, K S ) = ∑ ( x − K S N (i, x)), M x=KS and z-th statistical moment below the threshold − K s : m z− (i,− K S ) =

−KS

∑ (x+K

x=− B

z S

1 N (i, x)), M

classification. To optimize the algorithm the first, second, and the third moment for various values of K C were investigated. As the optimization constraint the minimum number of leads containing only elevations as being falsely classified as those containing depressions and the minimum number of leads containing only depressions as being falsely classified as containing elevations was chosen. The optimal values for K C according to optimization constraints are: 2 × 10 3 ( μV ) for the first, 75 × 10 3 ( μV ) 2 for the second, and 3.75 × 10 6 ( μV ) 3 for the third moment. An example in Fig. 2 demonstrates detection of a lead orientation.

(5)

are constructed, where z denotes moment used, N(i,x) represents number of samples with value x in the histogram, M is number of samples of d(i,k), and B=1500 μV defines the bounds between which the histogram is constructed. From these two moments the algorithm determines the lead orientation using following rule: 1 ⎧ + − ⎪ p : if (mz (i, K S ) − mz (i,− K S ) > M K C ) ⎪ 1 ⎪ O(i ) = ⎨n : if (mz+ (i, K S ) − mz− (i,− K S ) < − KC ) M ⎪ ⎪u : otherwise, ⎪ ⎩

where p, n, and u denote positive, negative and uncertain orientation respectively, and K C is the threshold for lead

(6)

Fig. 2 Histogram of the ST deviation function of the first lead, d(1,k), of record s30661 of the LTST DB. Ischemic episodes in this lead are depressions. See text.

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An algorithm for classification of ambulatory ECG leads according to type of transient ischemic episodes

III. RESULTS Table 1 summarizes results of the ECG lead classification using the first, second and the third moment and optimal thresholds K C . The results show that the algorithm using the first, second or the third moment, correctly classified all 9 leads with elevations as having positive orientation. The algorithm, using the first moment, correctly classified 86 out of 90 leads with depressions as having negative orientation, while three leads were classified as having positive orientation, and one as uncertain. Using the second (third) moment, the algorithm correctly classified 87 (89) leads with depressions as having negative orientation, while three (one) leads were classified as uncertain. Regardless of the moment used, the classification of the leads with mixed type of episodes was poor. The classification of the leads without episodes showed, that the best results were obtained using the third moment, when the algorithm classified 15 out of 42 leads as uncertain.

37

such leads. Larger number of episodes of one type than of the other prevails in such a way that the orientation is shown as either positive or negative. The developed algorithm also did not perform well while classifying leads containing no ischemic episodes. To better evaluate leads with mixed type of episodes and leads containing no episodes the rule (6) will need to be improved and more sophisticated method for determining the lead orientation will be investigated. Although, the best results were achieved using the third moment, the choice of the moment to use is predominantly dependent on the application for which it is to be used. In applications that would follow the protocol A of the LTST DB the use of the lower amplitude thresholds might be preferable. In this case the use of the second or the first moment might be desirable. We conclude that the algorithm developed showed nice performance in classification of ECG leads, will be improved, and could be a valuable tool to determine the severeness of ischemic heart disease.

Table 1 Results of the ECG lead classification using the first, second and the third moment with optimal threshold according to the reference annotations for the protocol B of the LTST DB. See text. Positive

REFERENCES

Negative

Uncertain

1.

0 86 2 24

0 1 1 8

2.

0 87 2 20

0 3 0 12

0 89 2 18

0 1 0 15

First moment Elevations Depressions Mixed No episodes

9 3 2 10

3.

Second moment Elevations Depressions Mixed No episodes

9 0 3 10 Third moment

Elevations Depressions Mixed No episodes

9 0 3 9

IV. DISCUSSION The results showed that the algorithm developed is efficient in classifying ECG leads with only elevated or depressed transient ischemic ST segment episodes. Using the third moment, almost all leads with either elevations or depressions were correctly classified. Main reason for uncertain classification of leads with mixed types of episodes is due to the different number of episodes of each type in

4. 5. 6.

Jager F, Taddei A et al (2003) Long-term ST database: a reference for the development and evaluation of automated ischaemia detectors and for the study of the dynamics of myocardial ischaemia. Med Biol Eng Comput 41: 172-182. Berger PB (2006) Acute Myocardial Infarction. Acp Medicine http://www.acpmedicine.com/dxrx/dxrx0108.htm Kleber AG (2003) ST segment elevation in electrocardiogram: a sign of myocardial ischemia. Cardiovasc Res 45: 111118. Wang K et al (2003) ST-Segment Elevation in Conditions Other Than Acute Myocardial Infarction. N Engl J Med 349: 2128-2135. Smrdel A, Jager F (2004) Automated detection of transient ST-segment episodes in 24 h electrocardiograms. Med Biol Eng Comput 42: 303-311. Smrdel A (2004) Robustno avtomatsko odkrivanje prehodnih epizod segmenta ST v 24-urnih elektrokardiogramih. PhD Thesis, Faculty of Computer and Information Science, University of Ljubljana. Author: Institution: Address: City: Country: E-mail:

Ales Smrdel Faculty of Computer and Information Science Trzaska 25 Ljubljana Slovenia [email protected]

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Assessment of the Heart Rate Variability during Arousal from Sleep by Cohen’s Class Time-Frequency Distributions M.O. Mendez 1, A.M. Bianchi1 , O.P. Villantieri1 and S. Cerutti1 1

Bioengineering Department, Politecnico di Milano, Milano, Italy

Abstract— Arousal from sleep is a normal physiologic event which produces well defined changes in the sympatho-vagal balance. Arousal from sleep is related to sleep fragmentation and some sleep disorders as obstructive sleep apnea. However when repetitive arousals are found during sleep time, bad sleep quality and as consequence sleepiness during the day are associated. We studied the dynamic of the HRV during arousal accompanied by muscular activity. Ten isolated arousals free from any pathologic event where studied. Three TimeFrequency distributions (TFDs), Born-Jordan, Choi-Williams and Smooth Pseudo Wigner-Ville Distributions, were analyzed in order to evaluate their performance during arousal episodes. The three TFDs showed the same performance when analytic HRV signal is used. LF component suggests a major participation of the sympathetic activity at the beginning of the arousal episode while HF component suggests a major role of the parasympathetic drive at after arousal episode. Keywords— Sympatho-vagal balance, Time-Frequency Distribution, Obstructive Sleep Apnea.

I. INTRODUCTION Sleep is an unconscious process where the human being interacts with his inner world and interaction with real worldis basically vanished. When we have a restorative sleep, we wake with energy to do all our daily tasks. However, sleep can be disturbed by different causes that range from stress until physiological pathologies as obstructive sleep apnea. Arousal from sleep is a natural physiological event that appears during both the normal sleep and pathologic episodes. Arousal from sleep has a very close relationship with sleep fragmentation since repetitive arousals from sleep produce a low sleep quality. Classical symptoms caused by a disrupted normal sleep are daily sleepiness, memory impairment and low concentration. In addition when arousal from sleep are related to noxious respiratory pathologies as obstructive sleep apnea, normal physiological levels can be altered even during wakefulness. Consequences of diurnal hypertension until heart failure can occur. Arousals from sleep have two main functions, activating sensory organs to monitor the environment and bolstering physiological system up to overcome noxious events [1]. Arousal from sleep is defined from the cortical electroencephalogram waves. Some definitions can be found in literature were spindles, k-complexes are part of

the arousal hierarchy as arousal precursors. An arousal episode is defined as a sudden increment in the EEG waves with at least thee seconds and not superior to 10 seconds. In addition, the shift frequency includes theta, alpha or frequencies higher that 16 Hz. In REM sleep an arousal must be accompanied by muscular activity. A complete arousal description is found in [2]. Arousals from sleep produce changes in heart rate. Heart rate presents increment during arousal episodes due to a withdrawal of the parasympathetic flow and a strong activation of sympathetic activity. Effects of arousal from sleep in sympatho-vagal balance have been widely studied as during NREM sleep and with inducted arousals [1,3-4]. On the other hand, in the past decades has been found a tie relationship between the autonomic nervous system and the spectral components of the heart rate variability. Therefore, methods of spectral decomposition represent a non invasive tool to evaluate the behavior of the of the autonomic nervous system. Heart rate fluctuations range between 0 and about 0.5 Hz. Frequency range between 0.15 – 0.5 Hz is directly correlated with the vagal flow, while range between 0.02 – 0.15 represent mainly the sympathetic activity [5]. The classical method to analyse the spectral components of a signals is the Fourier transform. However, this approach does not take in account the temporal evolution of the spectral components. In addition, arousal episodes produce a transitory reflex of the sympathetic muscle which is reflected as a non stationarity in the heart rate. Approaches as Wavelets transform, Time-variant autoregressive models and Time-Frequency Distributions (TFD) allow to evaluate the temporal dynamic of the signal fluctuation and are suitable to evaluate transitories changes as those present in the heart rate variability during arousal events. TFD evaluate the Fourier transform of the temporal autocorrelation. In other words, they evaluate the Fourier transform of the autocorrelation function without expected operator (Wigner-Ville Distribution). This evaluation enables to the TFD to capture the evolution of the spectrum at each sample, but in multi-component signals spurious frequency components appear. In order to reduce the spurious terms, some smooth functions (Kernels) have been incorporated inside to the Wigner-Ville Distribution. Each kernel represent a Time-Frequency Distribution and attain to specific properties such as time-frequency invariance, finite support, etc. Cohen’s class TFD is a well defined group of

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 30–33, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Assessment of the Heart Rate Variability during Arousal from Sleep by Cohen’s Class Time-Frequency Distributions

kernels that satisfy the time-frequency invariance property. This means that if a signal x(t) is delayed in time or modulated in frequency then its TFR will be delayed in time and shifted in frequency. This is an important property when physiological signals are analyzed [6]. The aim of this study is evaluate beat-by-beat the dynamic evolution of the autonomic nervous system. BornJordan, Choi-Williams and Smooth Pseudo Wigner-Ville Distribution which are part of the Cohen’s class are tested on synthetic signal and HRV sequence during arousal episode. We evaluated the goodness of each distribution to assess the dynamic changes of the HRV fluctuation in arousal episodes. II. MATERIAL AND METHODS Five overnight polysomnographic recordings were obtained from five healthy subjects. The subjects were 48±5 year old, Body Mass Index was 36±2 Kg/m2. Data were obtained using a polymnosograph Heritage Digital PSG Grass Telefactor. All signals were acquire with a sampling frequency of 100 Hz. Sleep stages were evaluated according to the standard clinical criteria [7]. Arousals were identified from EEG C4/A1 channel during stage 2 by expert personal, in agreement with the definition given in [2]. Ten arousal with muscular activity were selected free of noise and distant of any pathologic event (OSA or PLM). Therefore, the RR intervals were searched and detected from ECG channel by a derivative algorithm. Due to the low sampling frequency a better detection of R peaks was obtained by a parabolic interpolation. RR time series were verified and manually corrected where misdetections occurred and when extrasystoles happened the corresponding portion of the signal was discarded. Intervals of 2 min and 30 sec as baseline and the same interval as recovery after arousal were taken. A. Method Development Cohen’s Class Time-Frequency Distributions (TFD) of a signal x(t) is defined as:

⎛ τ⎞ ⎛ τ⎞ C x (t , f ) = ∫∫ φ (t − t ' ,τ ) x * ⎜ t '− ⎟ x⎜ t '+ ⎟e − j 2πfτ dt ' dτ ⎝ 2⎠ ⎝ 2⎠ (1) Where φ (θ ,τ ) is a function labeled kernel. By choosing different kernels, different features of the distributions are obtained. From here there is an infinite number of distributions that can be obtained. The TFD are defined according

31

to the kernel. Smooth Pseudo Wigner-Ville Distribution is characterized by independent smoothing functions, in time and in frequency originated by γ (t ) and η ⎛⎜ τ ⎞⎟η * ⎛⎜ − τ ⎞⎟ ⎝2⎠ ⎝ 2⎠ windows respectively, where the kernel function is:

⎛τ ⎞ ⎛ τ ⎞ ϕ ( t ,τ ) = γ ( t )η ⎜ ⎟η * ⎜ − ⎟ ⎝2⎠

⎝

2⎠

(2)

Choi and Williams Distribution is defined as:

ϕ ( t ,τ ) =

⎡ σ σ 1 exp ⎢ − 4π τ ⎣⎢ 4

2 ⎛t⎞ ⎤ ⎜ ⎟ ⎥ ⎝ τ ⎠ ⎦⎥

(3)

The scaling factor σ determines the cross-terms suppression, time and frequency resolution and concentration of auto-terms. High value of σ gives a good definition of autoterms and low cross-terms suppression, while low values of σ reduces cross-terms and spread out the auto-terms. Born-Jordan Distribution (BJD) maintains most of the attractive properties due to associates mixed products of time and frequency. The distribution had been used as bases for creating other distributions, or used for evaluating new distributions proposed. BJD is defined as:

⎧1 ⎪ , ϕ (t ,τ ) = ⎨ τ ⎪0, ⎩

t / τ 1/ 2

Arousal from sleep produce a strong and rapid change in the HRV signal. We are interesting in analyzing the ability of this TFD to follow this fast changes. In order to test the capacity of the different TFD we generate a tri-component synthetic real signal in the following way:

⎧sin(2πf1n), 32 ≤ n ≤ 192 ⎪sin(2πf n), 193 ≤ n ≤ 319 ⎪ 2 i= ⎨ ⎪sin(2πf 3 n), 320 ≤ n ≤ 480 ⎪⎩0, otherwise

(5)

Where f1=0.1 Hz, f2=0.25 Hz and f3=0.4 Hz In order to reduce the cross terms produced by the negative frequencies, Hilbert Transform was applied to the synthetic sequence. The sampling frequency of the synthetic signals was 4 Hz and 512 samples. The TFR parameters for SPWV were : smooth time window, hamming 21 samples; smooth frequency window Hamming 129 samples. For CWD a fixed σ = 1. Three frequency bands, A (0.35 –

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M.O. Mendez, A.M. Bianchi, O.P. Villantieri and S. Cerutti

0.45 Hz), B (0.15 – 0.25 Hz) and C (0.05 – 0.1 Hz) across all time were created in order to have a clear indication of the instantaneous power in each band. These bands show the interference terms attenuation and negative components. Each band and the total frequency range (0-0.5 Hz) were integrated across the frequency axis with the intention of comparing the real time evolution of the instantaneous power of the signal and the one obtained with the TFR. The results of the TFRs are showed by means of an image, the energy range is plotted in a gray scale of 256 values. B. Arousal Data Resulting RR sequences were re-sampled at 2 Hz by cubic spline interpolation and detrended. Therefore, to each RR sequence was applied Hilbert Transform in order to obtain an analytic signal. After that, SPWVD was used to obtain the evolution of RR power at different frequencies and times. Then, it was computed the time evolution of the classical heart rate variability indexes: (PT) total power (0.005-0.5 Hz), (VLF) very low frequency (0.005-0.04 Hz) ; (LF) low frequency (0.04-0.15 Hz); (HF) high frequency (0.15-0.4 Hz); and low to high frequency ratio (LF/HF). All spectral powers were computed in absolute units. The representation and spectral indexes was obtained using the absolute values of the distribution. The data were synchronized with the occurrence of the minimum RR value. Thereafter, an ensemble average was obtained for each spectral index and RR intervals. Each sequence was normalized as the percentage of change respect to the mean of the first 20 seconds of each sequence. All the indexes values were given as mean ± standard deviation. Segments of 180 points from data and spectral indexes were analyzed. III. RESULTS Figure 1 shows three sinusoids at different times and frequencies according to Equation 5. Signal components are clearly separated and fine represented by the three distributions in the time-frequency plane (upper panel). The results are so similar that is almost impossible distinguish among them by their time-frequency representation. From the middle panel, we can observe that the instantaneous power in A, B and C bands is totally smoothed by the three distributions. Finally, when we compare the instantaneous power of the real signal and the instantaneous power evaluated from the timefrequency energy plane, all TFDs follow in mean the real instantaneous power (lower panel). However, most important is to recognize that TFDs followed with high time resolution

Figure 1. Time-Frequency analysis of a synthetic signal composed by three sinusoids after the Hilbert transformation. The first row shows the time evolution of the PSD of the signal obtained by three Time-Frequency representations, Smooth Pseudo Wigner-Ville Distribution (SPWVD), ChoiWilliams Distribution (CWD) and Born-Jordan Distribution (BJD). The second row depicts the instantaneous frequency for A (dashed line), B (black line) and C (gray line) frequency bands. The third row present the instantaneous power for the whole frequency axis, gray line represents the theoretical instantaneous power while black line is the one obtained after integrating the PSD respect to the frequency axis.

the changes the changes in frequency presented in the synthetic signal. Figure 2 presents mean and SE of time evolution of the spectral indexes of HRV for arousals from sleep during stage two sleep. The series are presented as percentage variations respect to the baseline (see method). RR intervals present a fast decrement which reaches its minimum value around seven seconds after the beginning of the arousal episode, after that it begins a recovery phase over-passing the baseline and returning to the base line 20 seconds later. RR intervals, have significant lower values respect to the base line during 9 to 15 seconds. HF component has a decrement immediately when an arousal happens during the first 3 seconds, then a constant increment which arrive at the maximum value close at the final of the arousal. However, no significant difference were found. LF component presents a strong increment during arousal episode which shows its maximum value close to RR minimum and go back to baseline levels after 25 seconds. Significant differences respect to baseline are from 9 to 20 second. VLF component and LF to HF ratio showed an analogous performance as the LF component.

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Assessment of the Heart Rate Variability during Arousal from Sleep by Cohen’s Class Time-Frequency Distributions

33

but a smoothed version of this one (see Figure 1). When we deal with the HRV signal we are interested in the instantaneous frequency which describes the relations of the sympatho-vagal balance. Then, when we use an analytic version of a HRV signal it is indifferent to use any distribution. Changes in the sympatho-vagal balance during an arousal event are produced by both an increment in the symphatetic activity (LF increment) and a reduction in the parasympathetic activity (HF reduction). This fast and large change is caused by the activation of the sympathetic activity while the vagal tone seem not play an important role during the episode. On the Contrary, at the arousal end a tachycardia is observed where the vagus nerve play a major role. In conclusion TFDs are a fine tool to evaluate the dynamic that the autonomic nervous system presents during an arousal episode. When we work with analytic version of the HRV, the results suggest that it is indifferent applied any TFD. The sudden tachycardia observer at the beginning of an arousal seems caused mainly by the sympathetic activation. In the tachycardia after arousal episode parasympathetic activity seems to play a major role. Figure 2. Time evolution indexes of the heart rate variability parameters during arousal from sleep episode. Spectral indexes were evaluate by Smooth Pseudo Wigner-Ville distribution. Values are presented as mean value and standard error of the percentage changes respect to the baseline. Form the top to the bottom. RR intervals (RR), High frequency (HF), Low frequency (LF), Very low frequency (VLF) and Low to high frequency ratio (L/H). The window with * represents significant differences.

IV. DISCUSION AND CONCLUSIONS Born-Jordan, Choi-Williams and Smooth Pseudo Wigner-Ville distributions belonged to Quadratic Cohen Class Time-Frequency Distributions are used to evaluated the behavior of the autonomic nervous system during arousal form sleep episodes. Our main observations are : a) the three TFDs allow to evaluate with large time-frequency resolution the behavior of the heart rate variability even during transitory events. b) When we used an analytic signal, applying any of these TFDs during arousal episodes is indifferent. c) Arousal episodes produce a high increment in the LF/HF balance during arousal. However this change is mainly caused by a rise in LF. Physiological signals are real in nature. However, when we work with Time-Frequency distribution is recommended to use analytic signals in order to reduce the interference terms generated by the quadratic nature of this approach. Nevertheless the interference terms are necessary to retain fine properties found in BJD and CWD such as finite time support and marginals. Those properties are lost when we use analytic signals. If we integrate respect to the frequency axis, we do not obtain the instantaneous power of a signal

ACKNOWLEGEMENT This work was supported by the European project MY HEART

REFERENCES 1. 2. 3. 4. 5. 6. 7.

Halasz P, Terzano M. Liborio P, Bodizs R (2004) The Nature of Arousal in Sleep. J Sleep Res 13:1-13. Atlas Task Force of American Sleep Disorders Association (1992) EEG arousal: scoring rules and examples. Sleep 15: 174-184. Catcheside, et. al (2001) Acute Cardiovascular Responses to Arousal from Non-REM Sleep During Normoxia and Hypoxia. Sleep 24:895-902. Blasi A et.al. (2003) Cardiovascular Variability after Arousal from Sleep: Time-Varying spectral Analysis J Appl Physiol 95:1394-1404. Malliani A (1999) The Pattern of Sympathovagal Balance Explored in the Frequency Domain. News Physiol Sci 14: 111-117. Cohen L (1989) Time-Frequency Distributions – A Review. Proc. IEEE (77) 941-981. Rechtschaffen A, Kales AE (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Brain information Services/Brain Research Institute, UCLA, 1968. Author: Institute: Street: City: Country: Email:

Martin Mendez Politeci di Milano P.zza Leonardo da Vinci 32, 20133 Milan Italy [email protected]

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Autonomic Modulation of Ventricular Response by Exercise and Antiarrhythmic Drugs during Atrial Fibrillation VDA Corino1,2, LT Mainardi1, D Husser2, A Bollmann2 1

2

Department of Biomedical Engineering, Politecnico di Milano, Milano, Italy Department of Cardiology, University Hospital Magdeburg, Magdeburg, Germany

Abstract— Ventricular response (VR) during atrial fibrillation (AF) is a complex process that is influenced by the autonomic nervous system (ANS). Although antiarrhythmic drugs are known to have modulating ANS effects, these are not routinely evaluated in the clinical setting. Therefore, the purpose of this study is to characterize VR to exercise as ANS stimulus during AF and to evaluate possible modulating effects of antiarrhythmic drugs (flecainide and amiodarone). Seventeen patients (11 males, mean age 61±11 years), with persistent AF, underwent bicycle exercise testing before and after 3 – 5 days of oral flecainide (9 patients) or amiodarone (8 patients) loading. RR series were derived from ECG recordings and analyzed by means of time domain parameters (mean, SDNN, pNN50 and rMSSD) and non-linear methods assessing the predictability of the time series (level of predictability (P) and regularity (R)). The effect of exercise in VR modulation was evident both with and without antiarrhythmic drugs (p 4.5 ms) [6]. Acceleration related PRSA signal

Deceleration related PRSA signal Heart Beat Interval (ms)

Survivor

850

A

DC= 5.1ms

B

AC= -5.2ms

V. CONCLUSION The phase-rectified signal averaging method facilitates the detection of oscillations in biological signals; it provides a much better signal-to-noise ratio than the standard Fourier transformation [5,7]. Furthermore, it allows the separate investigation of heart rate deceleration related HRV and acceleration related HRV. As shown in [6], DC is a better risk predictor of mortality after myocardial infarction than not only the standard HRV parameters but also the left ventricular ejection fraction.

845

REFERENCES

840

1.

835

Non-survivor

Heart Beat Interval (ms)

2. 700 C

DC= 2.4ms

D

AC= -2.5ms

695

3.

690

4. 5.

685

Non-survivor

865 Heart Beat Interval (ms)

41

E

DC= 2.5ms

F

AC= -5.0ms

6.

860

7. 855

8.

850 -60 -40 -20

0

i

20

40

59 -60 -40 -20

0

i

20

40 59

Fig. 3 Representative PRSA signals of 24-hour ECGs from post myocardial infarction patients. (A) and (B) are from a patient who survived the follow-up period, both DC and AC are normal. (C) and (D) are from a patient who died 3 month after the index infarction, both DC and AC are abnormal. (E) and (F) are from a patient who died 5 month after the index infarction, the PRSA signal-pattern are asymmetric, DC is abnormal but AC is normal. (From [6] with permission.)

Kleiger RE, Miller JP, Bigger JT et al. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. American Journal of Cardiology 1987; 59: 256-62. Task Force of the European Society of Cardiology and the American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 1996; 93: 1043-65. Schmidt G, Malik M, Barthel P et al. Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 1999; 353: 1390-6. Barthel P, Schneider R, Bauer A et al. Risk Stratification After Acute Myocardial Infarction by Heart Rate Turbulence. Circulation 2003; 108: 1221-6. Bauer A, Kantelhardt JW, Bunde A et al. Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Physica A 2006; 364: 423-34. Bauer A, Kantelhardt JW, Barthel P et al. Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 2006; 367:1674-81. Kantelhardt JW, Bauer A, Schumann AY et al. Phase-rectified signal averaging for the detection of quasi-periodicities and the prediction of cardiovascular risk. Chaos (in press). Bauer A, Deisenhofer I, Schneider R et al. Effects of circumferential or segmental pulmonary vein ablation for paroxysmal atrial fibrillation on cardiac autonomic function. Heart Rhythm 2006; 3: 1428-35. Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Raphael Schneider Munich University of Technology, 1st Medical Clinic Ismaninger Str. 22 81675 Munich Germany [email protected]

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QT Intervals Are Prolonging Simultaneously with Increasing Heart Rate during Dynamical Experiment in Healthy Horses P. Kozelek, J. Holcik Czech Technical University in Prague, Faculty of Biomedical Engineering, nam. Sitna 3105, 27201 Kladno E-mail:[email protected], Phone: +420 312 608 213, Fax: +420 312 608 204 Abstract – Prolonging of QT intervals was published numerously and it is considered as a significant factor in prediction of sudden death. Available sources are occupied by analysis of static re-cords, i.e. without transient processes. We have recorded ECG data in horses that show clear prolonging of QT intervals during increasing heart rate in dynamical experiment. Generally speaking it is suggested as great risk of sudden heart failure. Paradoxically those records were measured in well trained horses. We suppose that such a phenomenon is caused by changes in nervous control of a heart. We have developed several model structures of QT intervals control. Simulation results indicate that generally accepted attitude to QT intervals control is misguiding or incomplete. We have proved theoretically that the abnormalities are caused by variant sensitivity of ventricular cells to sympathetic and parasympathetic during repolarisation phase. I. INTRODUCTION

Past studies on controlling the myocardium based on the cardiovascular system anatomy show that there are two mechanisms (stimulating and inhibiting) controlling performance of heart in organism. The task of our project was to describe mathematically the sympathetic (stimulating) and vagal (inhibiting) activities in a vegetative part of nervous system. Direct measurement of electro-chemical activity of both branches would be very complicated considering practical reasons (invasive measurement; difficulties in connecting the measuring electrodes to the nervous fibres outside of laboratory environment etc.). Therefore, we decided to use data from indirect measurements through the activity of organs, which are controlled by the vegetative nervous system. The anatomy of equine heart shows that open ends of vegetative nerves have a great density close to the sine node which is the basic source of electrical impulses in heart muscle and determines a heart rate. Thus sine node also determines the length of RR intervals in ECG. RR intervals can serve as an indirect indicator of common sympathetic and parasympathetic activity. In our work we assumed mutually independent activities of both branches. Two independent controlling mechanisms are fully described by two signals, therefore, we have to define another nervous activ-

ity indicator. There are open nervous ends of both vegetative branches in equine heart ventricles. That is why a suitable solution for defining another nervous activity indicator was choosing a sequence of QT intervals (time of spreading the electrical excitation through tissue of myocardium ventricles). Based on knowledge of the sequences of RR and QT intervals we designed a model of a myocardium control that could help to explain the causes of control mechanisms of the heart performance [4]. II. METHODS

Block diagram of the model structure is depicted in Fig. 1. As follows from our previous studies [1], [4] we used the formula

RR (t ) = RRSAU − k SR N S (t ) + k PR N P (t )

(1)

for generating sequences of RR intervals. RRSAU is a basic heart period of sine node and NS and NP represent sympathetic and parasympathetic activity levels. kSR, kPR are multiplicative parameters that express levels of influence of each neural branch upon the duration of RR intervals. Similarly,

QT (t ) = QT0 − k SQ N S (t − τ SQ ) + + k PQ N P (t − τ PQ )

(2)

describes an equation generating QT intervals where τSQ and τPQ are delays in sympathetic and parasympathetic neural branches in heart ventricles and kSQ, kPQ are multiplicative parameters, similar to those in the eq. (1). QT0 is a basic length of QT interval at neural ventricular blockade. Both

Fig. 1: Principle structure of the cardiovascular system control

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 62–65, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

QT Intervals Are Prolonging Simultaneously with Increasing Heart Rate during Dynamical Experiment in Healthy Horses

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the delays are connected with the finite velocity of nervous stimulation spreading. The aim of extending the described model was to find the internal structure of the subsystems SYM and PSYM (see Fig. 1) and their mutual relationship. The models for simulating static and dynamic properties of both the types of nerves fibres have structures depicted in Fig. 3, as published in [2] and [3]. First of all, it was necessary to describe sensitivity of the fibres on their stimulation represented by input signal NE. In our model, we have used bottom-limited piecewise linear function (Fig. 2) ⎧ ⎪a N + bS , P N S ,P = ⎨ S ,P E ⎪ 0 ⎩

if N E > −

bS , P

aS ,P otherwise

Fig. 2: Sympathetic and/or parasympathetic sensitivities, NS, NP (3)

where indexes “S” and/or “P” represent sympathetic and parasympathetic branch, aS,P is the sensitivity coefficient. Inertia of the nerves is modelled by the first-order low-pass filter described by the frequency response

F ( jω ) =

k T X jω + 1

⋅ e - jωτ X

(4)

where ω represents a frequency, TX is a time constant of the filter, τX is a unit delay and k is a gain of filter. The inertia is associated with the limited delay in response of the cells to their excitation. Finally, the “time-delay” block t represents a final velocity of spreading of the excitation along nervous threads and/or heart tissue. Input signal NE represents response of the neural feedback to impulse stimulation. It is described as

⎧ ⎡ ⎛ 2π π⎞ ⎤ (t − t1 ) − ⎟ + 1⎥, ⎪ A.⎢sin ⎜ 2⎠ ⎦ ⎪ ⎣ ⎝ T if t1 ≤ t ≤ t1 + T NE = ⎨ ⎪ ⎪ 0, otherwise, ⎩

Fig. 3: Basic structure of nervous fibres' model

Fig. 4: Input signal NE

(5)

where T is a duration of the input impulse and t1 represents its lag after some reference starting point. Fig. 5 shows a structure of the nervous heart control. It is based on the hypothesis that QT intervals are not controlled by the nervous activity only, but we can identify an indirect dependency of QT intervals on heart rate and its variability. Fig. 5: Detail structure of nervous control

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64

P. Kozelek, J. Holcik

objective function

kS

objective function

kS

kP

kP

h

opti ma l path

lp at

op

kS = kP

tim

a

optimum k S = kP

optimum

Fig. 7: Schematic explanation of different behaviour in equine heart

parameters (record 1 – left, record 2 – right)

ventricles (record 1 – left, record 2 – right)

0.1

0.1

0.08

0.08 Objective function

Objective function

Fig. 6: Experimental and simulated data generated by the optimized

0.06 0.04 0.02 Optimum

0 -6

0 -2

kPQ -5

-4

-6

-4 k SQ

0.06 0.04 0.02 Optimum

0 -6

0 -2

kPQ -5

-4

-6

-4 k SQ

Fig. 8: Objective functions for different values of gain factors kSQ, kPQ.

III. RESULTS

The simulation results have been compared to 4 most representative sets of experimental data. The criterion for choosing records was noiseless signal with considerable changes in the sequences of RR and QT intervals as responses to impulse stimulation. The aim of the work is to define properties of controlling subsystems, we have identified some of the model parametres as time constants of the filters (TSRp, TPRp, TSQp, TPQp and/or TSRs, TPRs, TSQs, TPQs), time delays (τSQp, τPQp and/or τSQs, τPQs) and gain factors (kSQp, kPQp and/or kSQs, kPQs). We used Matlab® Optimization Toolbox as an optimization tool. A root mean square error between simulated and real experimental data has been used for an optimization and its minimum was searched by the gradient method. The identification results for two different types of records are summarized in Table 1:

Table 1: Summary of optimized parameters for two different relationships between sequences of RR and QT intervals record 1 (velvet - s el 1 - 2002-04-24) 1. TSR = 25 s

record 2 (nikita - s el - 2002-04-24) 2. TSR = 4 s

3. TPR = 25 s

4. TPR = 4 s

5. TSQ = 19 s

6. TSQ = 18 s

7. TPQ = 17 s

8. TPQ = 18 s

9. τSQ = 18 s

10. τSQ = 4 s

11. τPQ = 20 s

12. τPQ = 1.2 s

13. kSQ = – 5.1

14. kSQ = – 4.2

15. kPQ = – 4.6

16. kPQ = – 4.6

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QT Intervals Are Prolonging Simultaneously with Increasing Heart Rate during Dynamical Experiment in Healthy Horses

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a) direct dependency QT on RR intervals – shortening of the RR intervals is followed by the shortening of QT intervals (Figure 6-left) b) relationship between RR and QT that is not explained yet – shortening of the RR causes almost immediate prolonging of the sequences of QT intervals (Figure 6-right). IV. CONCLUSIONS

Having identified model parameters by means of computer simulations we are able to explain fundamental causes of various behaviour of the QT intervals. We recognised almost linear dependency with positive slope constant between optimum parameters of τSQ, τPQ, and TSQ, TPQ,. It is due to the fact that the developed model uses linear subsystems only (the non-linear functions NS = NS(NE) and NP = NP(NE) are used in their linear parts only) and the input signal NE is used for both sympathetic and parasympathetic branch. We have proved experimentally that the simple shape of the QT interval sequences with one local extreme is generated by the model using very similar values of τSQ, τPQ and TSQ, TPQ in both the neural branches. If the supposition about the similarity of the above mentioned parameters is not valid then the signals NS, NP are mutually shifted in time. The mutual shift will cause a change of the QT sequence shape. In the case, one local extreme is substituted by biphasic waveform with local maximum and minimum (Fig. 9). Dependency of parameters kPQ, kSQ can be approximated well by a linear relationship with a negative slope constant (see the x-y projection of the optimum path in Fig. 7 and Fig. 8) kSQ = a.kPQ + b,

(6)

where the estimated values of coefficients a = −2 and b = −13.5 are roughly valid for all analysed records. If we suppose the simplified criteria τSQ = τPQ and TSQ = TP, then the breaking point between the direct (Fig. 6-left) and inverse (Fig. 6-right) dependency of QT on RR intervals is set for kSQ = kPQ = −4.5. Then for kSQ > kPQ we observe the direct and for kSQ < kPQ the inverse dependency of QT on RR intervals.

Fig. 9: Bi-phase sequences of QT intervals (heda1)

ACKNOWLEDGEMENT The research was granted by the project of Internal Grant Competition in Czech Technical University in Prague.

REFERENCES 1.

2. 3.

Holcik, J., Kozelek, P., Hanak, J. and Sedlinska, M.: Mathematical Modelling as a Tool for Recognition of Causes of Disorders in QT/RR Interval Relationship in Equine ECG. Proc. of PRIA2004, St. Peterburg, Russia, part.III, p.688-691. Van der Voorde, B.J.: Modeling The Baroreflex - a system analysis approach, p.10-59, 136-178. Amsterdam, Netherlands, September 1992. Holcik, J., Kozelek, P., Jirina, M., Hanak, J., Sedlinska, M.: Open-loop Model of Equine Heart Control, 13th NordicBaltic Conference on Biomedical Engineering and Medical Physics, vol. 9, pp. 297–298. ISSN 1680-0737 Author: Institute: Street: City: Country: Email:

Petr Kozelek Czech Technical University in Prague nam. Sitna 3105 272 01 Kladno Czech Republic [email protected]

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Relative contribution of heart regions to the precordial ECGan inverse computational approach A.C. Linnenbank1,2, A. van Oosterom3, T.F. Oostendorp4, P.F.H.M. van Dessel5, A.C. van Rossum2,6, R. Coronel1, H.L. Tan1,5, J.M.T. de Bakker1,2,7 1

Heart Lung Center, Dept. of Exp. Cardiology, AMC, Amsterdam, Netherlands, 2 ICIN, Utrecht, Netherlands 3 Dept. of Cardiology, University of Lausanne, Switzerland, 4 Dept. of Biophysics, Radboud University, Nijmegen, Netherlands, 5 Dept. of Clinical Cardiology, AMC, Amsterdam, Netherlands, 6 Dept. of Cardiology, VUMC, Amsterdam, Netherlands, 7 Dept. of Cardiology, UMC, Utrecht, Netherlands

Abstract— With an inverse computational approach using a multi-lead ECG recording of normal sinus rhythm in a patient spread of activation and repolarization was computed. Using this timing information, contributions to the standard 12-lead ECG were computed for selected segments of the heart. The results show that in none of the precordial leads is the influence of the right ventricle larger than from the left. The electric activity of basal regions and the RVOT are relatively poorly represented in the standard 12-lead ECG. Keywords— body surface mapping, activation time imaging, action potential duration, inverse procedure.

I. INTRODUCTION It is generally assumed that the precordial lead V1 mainly reflects electrical activity from the right ventricle, V2 that of from the interventricular septum and that V3-V6 signals are dominated by the left ventricle. The relative contribution of these cardiac regions to the ECG can not be verified experimentally. Knowledge about the contribution of activation of various parts of the heart to the ECG is important to ascribe ECG abnormalities to certain locations of the heart. Diseases like the Brugada syndrome affect the entire heart but ECG characteristics suggest that abnormalities predominantly arise in the right ventricle (RV). To study the contributions of various parts of the heart to the normal 12-lead ECG we built a (mathematical) volume conduction model of a patient from whom multiple body surface leads were previously recorded. Torso, lungs and heart geometry were reconstructed from magnetic resonance images (MRI). A previously developed inverse method [1,2] was used to estimate the timing of depolarization and repolarization at 1737 nodes specifying the geometry of the heart. The heart was digitally segmented, with triangles added to close the cutting edges. The inversely computed

depolarization and repolarization times were used to specify the local source strength while computing the contributions stemming from these different segments. II. METHODS 65 Channels of ECG data were recorded from a 55 year old female patient. The recordings were made as part of a standard family screening for the presence of the Brugada syndrome. Prior to this test 10 minutes of baseline ECGs were recorded. At baseline the ECG was within normal range and the heart was shown to have no structural abnormalities by MRI.

Fig 1. Left: anterior view of torso, lungs and heart. Right: posterior view. Positions of recording electrodes are indicated by blue dots. Electrodes on other side are visible as gray dots. Lungs are gray. Myocardium is brown. On the right blood volumes connected to the left and right cavities are visible in red and blue respectively

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Relative contribution of heart regions to the precordial ECG-an inverse computational approach

A. MRI and triangulation. A standard cardiac MRI protocol was used to build a 3D numerical model of the heart, lungs and thorax of this patient (Fig. 1), as required for the inverse procedure. From the MRI data slices in the horizontal, transversal and sagital direction, short axis views, and a long axis view were selected. The short axis views were used to create a triangulation of the heart. The same set of slices was used to define the boundaries of the lungs close to the heart to avoid intersection of the organs. The other slices were used to define lung boundaries further away from the heart. Special software to mark points on the slices and convert those to 3D vertices and to combine all these vertices into consistent triangulation was custom written. The thorax was created by deforming an existing mesh (Judy from Poser 5, efrontier.com, Santa Cruz CA) to fit the boundaries in the MRI slices. The electrodes were placed on the thorax at the documented recording sites. B. ECG recordings During a 40 minutes procedure, a 65-lead ECG was continuously recorded at the locations of the Amsterdam lead system [3], at 2 kHz sampling rate, bit_step of 1/8 µV and 24 bits resolution (modified Active2, BioSemi, Amsterdam). Post processing of the signals included the following elements: averaging of 1 minute episodes including rejection of artefacts, reference to zero mean, appropriate baseline correction and selection of the signals elements. For the part of study reported here only the 10 minutes of baseline ECGs were used.

43

electrodes by minimizing the difference between measured and model based potentials. As the relation between activation time and source strength is non-linear, the problem involved constitutes a non-linear parameter estimation problem. Such problems demand the specification of an initial estimate of the solution. Next, the minimization is performed iteratively, for which, in this study, the Levenberg-Marquardt method was used. The quality of the inverse procedure relies heavily on the initial estimate. Several methods to obtain an initial estimate have been described in the literature [2,6]. In the current study we have used a method based on the intra-myocardial distance function as previously described [6,7]. In short, with this method the initial estimate is selected from the exhaustive search of all activation patterns resulting from activations in which, successively, each node is taken as a focus. For each focus the timing of the other nodes was computed from the known distance to the focus and an assumed propagation velocity. The inverse problem is mathematically ill-posed. This is overcome by including the surface Laplacian to constrain the spread of activation to physiologically realistic values [2]. III. RESULTS The inversely computed activation and repolarization times are shown in Figure 2. The earliest activation was

C. Inverse procedure The method used for estimating the timing of the activation at the surface of the ventricular mass was based on the equivalent source model, as used previously [1,2,4]. In short, a tranfer matrix from every source location on the heart to every point on the surface is computed by using the boundary element method. Forward computation of surface potential is performed by multiplying this transfer matrix by simulated action potentials (AP) whose timing and shape depend on activation and repolarization times. A single logistic function was used as a model for the action potential when estimating activation times only. When estimating both activation and repolarization this function was replaced by a model of the action potential that also depends on the repolarization time, specified by a combination of logistic functions [5]. The inverse procedure estimates the activation times at the ventricular surface from the measured potentials at the

Fig 2. Top left: estimated depolarization sequence. Top right: the estimated repolarization times. Below: two views of the heart, showing the difference between the timing of local repolarization and depolarization (APD). The arrows mark an area, which extends into the septum, that has unrealistically short APDs. Times on the color bars below the hearts are in ms

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44 A.C. Linnenbank, A. van Oosterom, T.F. Oostendorp, P.F.H.M. van Dessel, A.C. van Rossum, R. Coronel, H.L. Tan, J.M.T. de Bakker

Fig 3. Contributions to the ECG from the right ventricle (blue), the septum (green) and the left ventricle (red). In black the ECG that was generated by the entire heart. Division of the heart in indicated in the top right

found in the septum, the earliest epicardial activation at the RV free wall close to the septum. Latest activation was at the basal parts of the heart. Figure 2 shows an area in the apex, septum, and posterior apical wall where the repolarization is unrealistic early (arrows). Apart from this area the inversely computed timing is compatible with measured activation patterns [8] . The correspondence between the computed ECG and the measured ECG was excellent (not shown). The RMS difference of measured and simulated potentials was 0.04 mV during the QRS and even less during the T wave. Figure 3 shows the ECGs broken down to its constituent contributions from the LV, RV and septum. Figure 4 shows on the left an enlarged version of V1,V2 and V6 for the same data plus an investigation for the same leads into the contribution of various basal parts of the heart. IV. DISCUSSION The results demonstrate that the electric activity of the LV free wall provides the main contribution to all precordial leads. Even V1 is not dominated by the RV, but receives a contribution from the septum that is just as large, while having an opposite sign. The contribution of the left

Fig 4. Enlarged versions of V1,V2 and V6. On the left the contributing segments studied are: left ventricle (red), septum (green) and right (blue). On the right the RVOT (light blue), the basal part of the right ventricle (blue) and the basal part of the left ventricle (red). Black line indicates contribution of entire heart

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Relative contribution of heart regions to the precordial ECG-an inverse computational approach

ventricular free wall (red line in Fig. 3 and the left part of Fig. 4) matches in this case closely to the recorded V1 lead. In all leads of the 12-leads ECG, the contributions from the basal parts of the ventricles and of the RVOT are very small. The method presented here for studying the contributions to the ECG of selected regions differs in two major respects from looking at contribution maps [9] like the ones available in e.g. ECGSIM [10]. First, we used a realistic activation pattern during sinus rhythm and computed the ECG generated by an entire part of the heart. Second, we used closed surfaces to prevent border artefacts. V. LIMITATIONS A parameterized model of an AP was used that gives a reasonable good shape for action potential durations (APD) over 200ms. For shorter APDs the plateau has a downward slope. This not only influenced the ST and T-wave but may already be noticeable at the end of the QRS. Although the solutions for the repolarization of the baseline ECGs were acceptable when they converged, there were also initial conditions where they diverged into nonphysiological solutions, possibly as a consequence of an interaction of activation and repolarization times. In the solution shown above there is an area at the apex that has much shorter APDs than the surrounding area. This area yields a contribution to the surface ECG that is close to zero. This may be due to the more gradual character of the repolarization, both in time and in space. As a result the inverse estimation of repolarization may have to be regularized over larger areas than the activation. VI. CONCLUSIONS •

•

•

No single lead of the standard 12-lead ECG predominantly represents the electric activity of the RV. Even V1 receives equal or greater contributions from both the septum and the LV. The RVOT, and the basal parts of the LV and RV hardly contribute to the standard leads, at least not during sinus rhythm reported on in this study. To estimate the delay in, e.g., the RV multiple simultaneously recorded signals are required, supported by a dedicated inverse procedure. Estimation of activation (and repolarization) times by an inverse computation and a subsequent forward computation of a part of the heart, can give insight into the way that part contributes to the recorded ECG, information that can not be obtained in any other way.

45

ACKNOWLEDGMENT This study was supported by the Netherlands Heart Foundation grants 2002B087 and 2005B92

REFERENCES Cuppen, J.J.M. and A. van Oosterom, Model studies with the inversely calculated isochrones of ventricular depolarization. IEEE Trans Biomed Eng, 1984. BME-31: p. 652-659. 2. Huiskamp, G. and A. Van Oosterom, The depolarization sequence of the human heart surface computed from measured body surface potentials. IEEE Trans Biomed Eng, 1989. 35(12): p. 1047-1058. 3. SippensGroenewegen, A., et al., A radio-transparent carbon electrode array for body surface mapping during catherization. Proc 9th Ann Conf IEEE-EMBS, 1987: p. 178181. 4. van Oosterom, A. Genesis ot the T wave as based on an Equivalent Surface Source model. JElectrocardiol, 2001. 34 Supl, 217-227. 5. van Oosterom, A. and V. Jacquemet. A Parameterized Description of Transmembrane Potentials used in Forward and Inverse Procedures. in Int Conf Electrocardiol. 2005. Gdansk; Poland: Folia Cardiologica. 6. van Oosterom, A. and P. van Dam. The intra-myocardial distance function as used in the inverse computation of the timing of depolarization and repolarization. in Computers in Cardiology. 2005. 7. Linnenbank et al. Non invasive imaging of activation times during drug induced conduction changes. Proceedings of the World Congress on Medical Physics and Biomedical Engineering, Seoul, 2006. 8. Durrer, D et al. Total excitation of the Isolated Human Heart. Circulation. 1970 Jun;41(6):899-912. 9. van Oosterom, A and G.J. Huiskamp. The effect of Torso Inhomogenities on Body Surface Potantials Quantified using “Tailored” Geometry. J. Electrocardiol., 1989, 22, p 53-72. 10. van Oosterom, A. and T.F. Oostendorp. ECGSIM an Interactive tool for Simulating QRST Waveforms. Heart. 2004 Feb;90(2):165-8.

1.

Address of the corresponding author: Author: Institute: Street: City: Country: Email:

A.C. Linnenbank Dept. of Experimental and Clinical Cardiology, AMC Meibergdreef 15 Amsterdam Netherlands [email protected]

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Sample Entropy Analysis of Electrocardiograms to Characterize Recurrent Atrial Fibrillation R. Cervigon1, C. Sanchez1, J.M. Blas1, R. Alcaraz1, J. Mateo1 and J. Millet2 1

Universidad de Castilla-La Mancha. Innovation in Bioengineering Research Group (GIBI). DIEEAC, Cuenca, Spain 2 Universidad Politecnica de Valencia. Bioengineering Electronic Telemedicina, Valencia, Spain

Abstract— In a substantial number of patients atrial fibrillation (AF) recurs after successful electrical cardioversion, but at present there are no reliable clinical markers for confidently identifying the patients in which recurrence will occur within a short period of time. This study evaluates the predictive classification performance of Sample Entropy (SampEn) in the discrimination between recurrent and non-recurrent AF episodes. A validated database of 35 ECG recordings acquired from AF subjects undergoing cardioversion was used throughout the study, together with their known recurrence status at one month. SampEn was applied to these QRST-reduced electrocardiograms, to atrial activity (AA), and also to heart rate (R-R intervals). The sample entropy of R–R intervals was significantly reduced (p=0.043) in the recurrent AF episodes compared with maintenance sinus rhythm episodes. SampEn applied to the AA signal showed a opposite results, it was reduced with a significant increasing trend in the maintenance sinus rhythm episodes (p=0.017). There is a need for welldefined studies with larger patient groups in order to assess the entropy changes further and to look for possible changes, which might predict AF recurrence. Keywords— Atrial Fibrillation, Sample Entropy, Electrical Cardioversion.

I. INTRODUCTION Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. It affects 2% of the unselected adult population and between 6% and 8% of the population over 65 years of age [1,2]. It is the most common cardiac cause of stroke [3]. In addition, the rapid heart resulting from AF can cause a number of adverse outcomes, including congestive heart failure and tachycardia related cardiomyopathy [4], and the risk of mortality is double than in patients with sinus rhythm [5]. AF results from multiple, rapidly changing and spatially disorganized activation wavelets circulate more or less randomly across the atrial myocardium [6,7]. In the surface electrocardiogram, this uncoordinated atrial activity (AA) is reflected as a randomly variable baseline measurement in place of a well-defined P-wave, though in general the subsequent ventricular electrical activity is unaffected in morphology. The progression from normal sinus rhythm (NSR) to AF is not completely understood, though this transition is

often associated with either changes in autonomic tone, or the presence of very early Premature Atrial Contractions (PAC), or atrial tachycardia. Medications are only marginally effective in treating this arrhythmia, and have the potential for serious side effects, including life-threatening pro-arrhythmia. Most of the drugs used to control heart rate in AF do not improve effort tolerance [8], whereas the restoration of sinus rhythm has been shown to significantly improve it [9]. Furthermore, structural cardiac changes associated with AF have been shown to be reversible when sinus rhythm is restored [10]. However, following NSR restoration after successful electrical cardioversion (ECV), the recurrence of AF within a year is up to 60-75% of patients [11]. As a consequence, it is required a reliable predictor for NSR maintenance. A number of clinical studies have been already suggested long term maintenance of sinus rhythm post-cardioversion predictors. Some of them are: left atrial size [12], age, functional class, energy requirements [15], AF duration, and antiarrhythmic drugs [11], though their role for prediction of outcome following cardioversion is controversial. Recent reports have investigated the length of atrial refractory period as an index of effective ECV, but its efficacy is also unclear [12,13,14]. In addition, among factors contributing to genesis or maintenance of circulating wavelets, Autonomous Nervous System (ANS) seems to play a significant pro-arrhythmic role [16]. Table 1 Patients Clinical Characteristics Parameter Patients Men Underlying heart disease Antiarrhytmic Amiodarona Treatment Flecainida

NSR Maintenance 15 (57.14%) 9 (60%) 8 (53%) 12 (80%) 3 (20%)

Redundance AF 20 (43.86%) 16 (80%) 18 (90%) 16 (85%) 4 (15%)

The present study was conducted to analyze ECG signals from patients with persistent AF in order to extract reliable parameters to predict early AF recurrence after successful ECV. The technique employed for ECG analysis was based on the non linear analysis, specifically the entropy, which have been successfully employed to solve other physiologist

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 54–57, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Sample Entropy Analysis of Electrocardiograms to Characterize Recurrent Atrial Fibrillation

problems, as in the analysis of the heart rate variability where has already showed its potential in the prediction of cardiac risk [17,18,19]. II. MATERIALS AND METHODS A. Materials This study was carried out with a signal database including standard 12-lead ECG recordings from 35 patients diagnosed with persistent AF. These recordings were obtained in the Electrophysiological Laboratory, Hospital Clínico Universitario de Valencia, during ECV protocol. These signals consisted in an AF segment before cardioversion. All these signals were digitized at a sampling rate of 1KHz and 16-bit resolution. In order to process these signals, a 1 minute-length AF segment preceding the ECV was extracted for each patient. All patients with AF were monitored 4 weeks after cardioversion, where 15 out of 35 patients (42.86%) remained in NSR, whereas the other 20 patients (57.14%) turned back to AF. B. Preprocessing The analysis was applied to lead V1, which is the lead that shows higher amplitude of the atrial fibrillatory signal. Before applying entropy, all signals were preprocessed using a 50-Hz notch filter to cancel out mains interference, followed by a band-pass filter with cut-off frequencies of 0.5 and 60 Hz to remove baseline wandering and reduce thermal noise. Since the atrial and ventricular activities overlap spectrally, linear filtering techniques are not suitable for extraction of the fibrillatory signal from the surface ECG. Instead, subtraction of averaged QRST complexes needs to be performed producing a remaining atrial fibrillatory signal for further analysis. Although there are different techniques, it was used a fixed averaged QRST-complex for cancellation in individual leads. [14,15] C. Sample Entropy In this study, we have used Sample Entropy (SampEn) as a useful measure of regularity. This is a similar, but less biased, measure than the approximate entropy (ApEn) family of parameters [21] introduced by Pincus to quantify the regularity of finite length time series. The Sample Entropy can be calculated as follows. Consider the distance between two vectors as the maximum of the absolute differences between their components and fix a

55

threshold value r for determining when these vectors are close to each other, ApEn reflects the likelihood that sequences that are close to each other, i.e., within r, for m consecutive data points remain close when one more data point is known. Mathematically, ApEn is computed as follows: Let Xi = x1;…; xi ;...; xN represent a time series of length N. Consider the m-length vectors: Um(i)= xi;xi+1;...;xi+m-1. Let nim(r) represent the number of vectors um(j) within r of um(i). SampEn has the advantage of being less dependent on the time series length, showing relative consistency over a broader range of possible r, m, and N values. Starting from the definition of the entropy, it is defined:

SampEn(m, r , N ) = − ln

U m+1 ( r ) U m (r )

The differences between Um+1(r) and Cm+1(r), Um(r) and C (r) are the definition of the distance between two vectors as the maximum absolute difference between their components, the exclusion of self-matches, given a time series with N data points, only the first N-m vectors of length m, um(i), are considered, ensuring that, for 1≤i≤N-m, the vector um+1(i) of length m+1 is also defined. SampEn is precisely equal to the negative of the natural logarithm of the conditional probability that sequences close to each other for m consecutive data points will also be close to each other when one more point is added to each sequence. Larger SampEn values indicate greater independence, less predictability, hence greater complexity in the data. This, in turn, may imply that decreased complexity or greater regularity in the time series is not associated with disease. For the study discussed in this paper, SampEn is estimated using the widely established parameter values of m = 2, and r = 0.25%, where σ represents the standard deviation of the original data sequence, as suggested by Pincus [21]. It assigns higher entropy values to certain pathologic time series than to time series derived from free running physiologic systems under healthy conditions [18,19,20]. m

III. RESULTS The values of SampEn of the R–R intervals (SampEn_RR) were low in the patients with recurrences 1.980±0.012 compare to those that maintenance the sinus rhythm 1.993±0.013 (p < 0.043 Mann-Whitney test) (Fig. 1). The opposite tendency was obtained in the measure of SampEn of the AA (SampEn_AA) with, 1.794±0.135 in the recurrent group vs. 1.554±0.319 in the non recurrent group (p < 0.017, Mann-Whitney test) (Fig. 2).

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R. Cervigon, C. Sanchez, J.M. Blas, R. Alcaraz, J. Mateo and J. Millet

points. The area under the curve, measures the ability of the test to correctly classify and assess subjects with and without the disease, such that higher areas indicate higher performance rates. Using this features on a separately training set that quantify the total number of the subjects resulted 71.70 % accuracy with the SampEn_AA and 73.20% from the measure of the SampEn _RR.

2,01

SampEn RR

2,00

1,99

1,98

1,97

Table 2 ROC curve values obtained from SampEn 1,96 0

1

NoRecurrente-Recurrente

Fig. 1 Sample Entropy RR

Threshold

Se (%)

1.755 1.985

73.30 85.50

1-Sp (%) 70.00 62.00

Area 0.738 0.775

To increase the capacity of the prediction, these variables were introduced in a forward stepwise logistic regression model. With SampEn_RR >1.985 (OR 0.080, p=0.008) and SampEn_AA0. Initialize the U= [μi,k] RεN partition matrix randomly, where μi,k denotes the membership that the Zk data is generated by the i'th cluster. Repeat for l = 1, 2… . Step1: Calculate the parameters of the clusters. Calculate the centers and standard deviation of the Gaussian membership functions (the diagonal elements of the Fi covariance matrices) N

v

(l ) i

=

∑ (μ k =1 N

( l −1) m i ,k

∑ (μ k =1

) xk

( l −1) m i ,k

)

N

, σ

2(l ) i, j

=

∑ (μ k =1

( l −1) m i ,k

) ( x j ,k − v j ,k ) 2

N

∑ (μ k =1

(6)

( l −1) m i ,k

)

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Ayyoub Jafari, M.H. Morradi

Estimate the consequent probability parameters.

p( ci rj ) =

∑ ∑

k yk =ci N

k =1

(μ (jl,k−1) )m

(μ

(l −1) m j ,k

)

, 1 ≤ i ≤C, 1 ≤ j ≤ R

(7)

A priori probability of the cluster and the weight (impact) of the rules. P (ri ) =

1 N

N

∑ (μ k =1

( l −1) m i ,k

)

n

, wi = P (ri )∏ j =1

1

(8)

2πσ i2, j

Step2: Compute the distance measure D2i, k by (4). Step3: Update the partition matrix μi(,lk) =

1 R

∑ (D

i,k

j =1

, 1≤ i ≤ R , 1 ≤ k ≤ N

( zk , ri ) / D j , k ( zk , rj )) 2 /( m −1)

untill U ( l ) − U ( l −1) 〈ε

(9)

(10)

V. FEATURE SELECTION Using too many input variables may result in difficulties in the interpretability capabilities of the obtained classifier. Hence, selection of the relevant features is usually necessary. In this paper, the modified Fischer interclass separability method is used which is based on statistical properties of the data. The interclass separability criterion is based on the FB between-class and the FW within class covariance matrices that sum up to the total covariance of the data FT=FB+FW, where: FW = v0 =

R

∑

l =1

P ( rl ) F l , F B =

R

∑

l =1

P ( r l ) ( v l − v 0 ) T ( v l − v 0 ),

(10)

R

∑

l =1

P ( rl ) v

(11 )

l

J=

det ( FB ) det ( Fw )

(11)

The feature interclass seperatibility selection criterion is a trade-off between FW and FB (Eq.12). The importance of a feature is measured by leaving out the interested feature and calculating J for the reduced covariance matrices. The feature selection is a step-wise procedure, when in every step the least needed feature is deleted from the model [29]. VI. RESULTS To evaluate the method used in this study a HRECG database consisting of two groups of signals was selected. The first group contained 50 healthy volunteers’ HRECG records acquired by a digital data acquisition system,

ML785 PowerLab/8SP, with a sampling frequency of 2000Hz and a 16-bit analog-to-digital converter (ADC). The second group was consisted of semi-simulated HRECG signals with VLPs. In order to simulate each of these signals, three basic simulated waveforms resembling the VLP characteristics were added to XYZ leads of a basic HRECG record, a HRECG record without VLP. VLPs are low-amplitude signals (~1-20μV) with short duration (~550ms) and broadband spectrum (~40-250Hz) [11]. According to these characteristics, VLPs were simulated as colored Gaussian processes resembling better the real world signals. The basic VLP waveforms were added to the end part of the QRS complex of every heart beat of the XYZ leads belonging to the basic HRECG records. The position of the VLPs was varied randomly from beat to beat with respect to the fiducial mark, QRS peak [10, 11]. This HRECG database was divided into a training set, including thirty HRECG signals with VLPs and thirty without, and a test set consisting of 20 records without VLPs and 20 with. For a better training of the neural network and preserving its generalization, the training set was expanded; five sets containing 300 heart beats were selected from every HRECG record of training set randomly. Because of the fact that every HRECG record had at least 350 heart beats, the beat selection was done without replacement for each set. Therefore, an expanded training set consisting of 300 patterns was obtained. The performance of the VLP detection method was measured using conventional criteria i.e. the accuracy ACC, sensitivity SE, and specificity SP defined by ACC = 100 × (TP + TN ) / N

SE = 100 × TP /(TP + FN )

SP = 100 × TN /(TN + FP )

(12)

(13)

Where N, TP, TN, FP, and FN are respectively the total number of patterns, the number of true positive, the number of true negative, the number of false positive, and the number of false negative [6]. Using the expanded training set and the test set, the method based on the CWT and the Fuzzy Supervised Clustering system, introduced in Fig.2, was evaluated that showed good results for the test set. To investigate the performance of the VLP detection method proposed in this work, the conventional time-domain method (Simson's method) was applied to the test set; also, a method based on applying our system to the conventional time-domain features [4,13] was used to detect VLP. Table1 presents the results of the proposed method in comparison with Simson's method and applying a Proposed Fuzzy System to the conventional time-domain features, for the test set. In Simson's method, the balance between SE and SP can be controlled by choosing one, two, or three of the positive VLP criteria (QRST>114ms, D40>38ms, and V40 1 Hz) with hindered EMG bursts recorded at uterine corpus mechanical contractions. With progression of ripening, EMG pattern changes in the periods between EMG bursts. The EMG signal amplitude in those periods becomes lower and less dense and the EMG bursts at contractions more outstanding (Fig. 1, middle two rows). The process of reduction of EMG activity between uterine corpus mechanical contractions progresses until there is almost no EMG activity between EMG bursts between consecutive uterine contractions (Fig. 1, bottom row). Changes in EMG signal frequency contents are adequately reflected in corresponding PSD as presented in Figure 2. The EMG of an unripe cervix (Figure 2a) has three frequency groups: one around 2.4 Hz, the other around 1.2 HZ and the third below 1 Hz. With ripening of the cer-

Fig. 1: EMG as derived from the cervix at an initiation of a delivery in 4 women at different stage of the cervical ripeness: unripe cervix (phase 1), partially ripe cervix (phase 2 and 3) and ripe cervix (phase 4). The EMG amplitude scale differs between phases.

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Predictive value of EMG basal activity in the cervix at initiation of delivery in humans

a

b

c

d

133

Fig. 2: Power Spectrum Density charts corresponding to the EMG signals from Figure 1: a) unripe cervix; b) ripening cervix; c) ripening cervix; d) ripe cervix. Solid line represents PSD during EMG bursts, dashed line between bursts. Note that a) has a different horizontal scale, and d) has a different vertical scale.

vix, the first group diminishes, the second is still well expressed and the first increases in its power contents (Figure 2b and 2c). In a ripe cervix, only the first group of frequencies below 1 Hz is present (Figure 2d). B. Results of statistical analysis Statistical analysis showed that the average EMG amplitude URMSA and average median frequency MFA as the characteristic parameters of the selected intervals of the EMG basal activity are predictive of the cumulative Bishop Score CBS (p=0.017 for the model; adjusted R2=0.131). As illustrated in Fig. 3, both URMSA and MFA are negatively associated with Bishop Score (β =-0.364, p=0.013 for URMSA; and β =-0.045, p=0.045, for MFA). The cumulative Bishop Score value is high when both URMSA and MFA have low values and decreases when with increasing URMSA and/or MFA. No statistically significant association could be found among URMSA and MFA on one hand, and the individual Bishop Score components (p-values are for the model from LR test): cervical channel dilatation DILA, dichotomized as 2-3 vs. 0-1: p=0.104; cervical effacement EFFA, 2-3 vs. 01: p=0.105; and cervical consistency CONS, 2 vs. 0-1: p=0.311. Similarly, no statistically significant association was found with time to delivery (p=0.816 for the model), or with number of contractions (p=0.475 for the model). IV. DISCUSSION The focus of our study was on the cervical EMG basal activity. Statistical analysis confirms the observations resulting from Fig. 1 and Fig. 2. As seen from Fig. 3, the

Fig. 3: Association of EMG characteristic parameters URMSA and MFA with Cumulative Bishop Score. Local regression smoother is superimposed on the point-cloud. cervical EMG basal activity parameters (URMSA, MFA) relate to the Bishop cumulative value. At the onset of an induced labor, the average cervical EMG signal amplitude (URMSA) and the average median frequency (MFA) are negatively associated with the cumulative Bishop Score. Consequently, an obstetrician may expect a low cumulative Bishop Score value for the labor when EMG signal is of high amplitude (e.g., URMSA > 50 µV) and/or having high median frequency value (e.g., MFA >> 1 Hz). When presented on a monitor with a standardized scale, the EMG signal would be of high amplitude and of a dense trace. Conversely, high cumulative Bishop Score value is expected when both the EMG amplitude and the EMG median frequency have low values (e.g., URMSA < 25 µV and MFA < 0.5 Hz). In that case, the EMG signal would be of low amplitude and its polarity would change slowly. The results are in line with our previous findings [4,5,6,17]. V. CONCLUSIONS At the onset of an induced labor, EMG activity registered in the periods when there are no uterine contractions and no bursts in the cervical EMG signal is considered the EMG basal activity of the cervix. Its average amplitude (URMSA) and average median frequency (MFA) are negatively associated with the cumulative Bishop Score as assessed by an obstetrician at a digital check of the cervical (un)ripeness at the beginning of the labor. High URMSA and high MFA advo-

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D. Rudel, G. Vidmar, B. Leskosek and I. Verdenik

cate for low Bishop Score values, while low URMSA and low MFA advocate for high Bishop Score values. It may be concluded that to a certain extent, EMG signal parameters URMSA and MFA reflect the stage (level, status) of cervical ripeness and thus the readiness of the cervix for successful labor. Hence, an adequately processed cervical EMG signal, when visually presented to an obstetrician in a delivery room, could help him/her to better assess cervical ripeness at the onset of labor, thus supporting him/her in deciding how to proceed in conducting the labor.

8. 9.

10.

11.

ACKNOWLEDGMENT The study was supported by the Ministry of Science and technology of the Republic of Slovenia (grants L3-7365, J38759, J3-5342, J3-2361). The authors express their gratitude to Mr. Darko Oberzan, MKS Ltd. Ljubljana, for his help in EMG signal processing.

12.

13. 14.

REFERENCES 1. 2. 3.

4. 5. 6.

7.

Pajntar M, Roskar E, Rudel D. (1987) Electromyographyc observations on the human cervix during labor. Am J Obstet Gynecol 156(3): 691-697 Pajntar M. (1994) The Smooth Muscles of the Cervix in Labor. Eur J Obstet Gynecol Reprod Biol 55: 9-12 Olah KS. (1994) Changes in cervical electromyographic activity and their correlation with the cervical response to myometrial activity during labor. Europ J Obstet & Gynaecol Rprod Biol 57:157-9 Rudel D, Pajntar M. (1999) Active Contractions of the Cervix in the Latent Phase of Labor. Br J Obstet Gynaecol, 106: 446-52 Rudel D, Pajntar M. (1999) Contractions of the Cervix in the Latent Phase of Labor. Contemp Reviews in Obstet Gynaecol 11(4):271-9 Pajntar M, Leskosek B, Rudel D, Verdenik I. (2001) Contribution of cervical smooth muscle activity to the duration of latent and active phases of labor. Br J Obstet Gynaecol 108:1-6 Toutain PL, Garcia-Villar R, Hanzen C, Ruckebusch Y. (1983): Electrical and mehanical activity of the cervix in the ewe during pregnancy and parturition. J Reprod Fertil 68: 195-204.

15.

16.

17.

Garcia-Villar R, Toutain PL, Ruckebusch Y. (1984) Pattern of electrical activity of the ovine uterus and cervix from mating to parturition. J Reprod Fertil 72:143-52 Breeveld-Dwarkasing VN, Struijk PC, Lotgering FK, Eijskoot F, Kindahl H, van der Weijden GC, Taverne MA. (2003) Cervical dilatation related to uterine electromyographic activity and endocrinological changes during prostaglandin F(2alpha)induced parturition in cows. Biol Reprod. 68(2):536-42 Cavaco-Goncalves S, Marques CC, Horta AE, Figueroa JP. (2006) Increased cervical electrical activity during oestrus in progestagen treated ewes: Possible role in sperm transport. Anim Reprod Sci. 93(3-4):360-5 Uldbjerg N, Ulmsten U, Ekman G. (1983) The ripening of the human uterine cervix in terms of connective tissue biochemistry. In: Pitkin RM, Scott JR, Ulmsten U, Ueland K eds. Clin Obstet Gynecol No.1, Vol. 26. Philadelphia: Harper & Raw 14-26 Garfield RE, Saade G, Buhimschi C, Buhimschi I, Shi L, Shi SQ, Chwalisz K. (1998) Control and assessment of the uterus and cervix during pregnancy and labor. Hum Reprod Update 4(5):673-95 Bishop EH. (1964) Pelvic scoring for elective induction. Obstet Gynecol 24: 226 Serr DM, Porath-Furedi A, Rabau E, Zakunt H, Mannor S. (1968) Recording of electrical activity from the human cervix. J Obstet Gynaecol Br Cmwlth 75: 360-3 Hofmeister JF, Slocumb JC, Kottmann LM, Picciottino JB, Ellis DG. (1994) A Noninvasive Method for Recording the Electrical Activity of the Human Uteus in Vivo. Biomed Instrum Technol 28: 391-404 Leskosek B, Pajntar M, Rudel D. (1998) Time/frequency analysis of the uterine EMG in pregnancy and parturition in sheep. In: Magjarević R, ed. Biomedical measurement and instrumentation – BMI'98. Proc Vol 3, 8th Int IMEKO TC-13 Conf Measurement in Clinical Medicine & 12th Int Symp Biomed Eng Dubrovnik. Zagreb: KoREMA, 2003, pp 106-9 Pajntar M, Verdenik I. (1995) Electromyographic activity in cervices with very low Bishop score during labor. Int J Gynecol Obstet 49: 277-81

Drago Rudel MKS Electronic Systems Rozna dol. C.XVII/22b SI-1000 LJUBLJANA, SLOVENIA [email protected]

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Uterine Electromyography in Humans – Contractions, Labor, and Delivery R. E. Garfield and W. L. Maner University of Texas Medical Branch/Reproductive Science, Galveston, Texas, USA Abstract— Today’s maternal/fetal monitoring lacks the capability to diagnose labor and predict delivery. The objective of this work was to demonstrate that uterine electromyography (EMG) is proven to be a viable alternative to current monitoring techniques. Uterine EMG was monitored noninvasively and trans-abdominally from pregnant patients using surface electrodes. Several aspects of the uterine EMG were investigated: contraction plotting, diagnosing labor, and predicting delivery. Contractions were seen to correspond well with tocodynamometer- (TOCO-) plotted contractions. As well, increases in electrical activity were indicative of labor and imminent delivery. Uterine EMG could be a valuable tool for obstetricians if implemented on a routine basis in the clinic. Keywords— Uterus, electromyography, EMG, labor, diagnosis, prediction.

mometer (TOCO) has routinely been used in the clinic to measure contractions [13], it has been shown to have limited predictive capability [14]. Root-mean-square (RMS) signal processing has been established as a standard method for plotting signal amplitude changes [15]. Spectraltemporal mapping has been used successfully to identify spectral changes that occur in biological electrical signals [16, 17]. II. OBJECTIVES • •

I. INTRODUCTION Labor is the physiologic process by which a fetus is expelled from the uterus, and is defined loosely as regular uterine contractions accompanied by cervical effacement and dilation.[1] Preterm labor, defined as labor before 37 weeks’ gestation, is the most common obstetric complication and occurs in about 20% of pregnant women. In the United States alone, 10% of the 4 million infants born each year are premature. [2 and 3] At $1500 a day for neonatal intensive care, this constitutes a national health care expenditure well over $5 billion. [4] In addition, preterm labor accounts for 85% of infant mortality and 50% of infant neurologic disorders. Current tocolytic therapy has not decreased the rate of preterm delivery. It is argued that the failure of the current strategies to decrease the rate of preterm labor might be because once preterm labor is finally diagnosed, any therapeutic benefit is lost or temporary. Therefore, one of the keys to treating preterm labor would be early detection or prediction. What is called for is a better method of monitoring patient uterine contraction activity. Previous studies have established that the electrical activity of the myometrium is responsible for myometrial contractions [5, 6]. As well, extensive studies have been done in the last 60 years to monitor uterine contractility using the electrical activity measured from electrodes placed on the uterus [7-9]. However, more recent studies indicate that uterine EMG activity can actually be monitored accurately from the abdominal surface [10-12]. Although tocodyna-

•

To determine if uterine contraction events plotted using uterine electromyography (EMG) data, correlate with TOCO-plotted contraction events. To compare uterine electromyography of labor patients to ante partum patients. To determine whether delivery can be predicted using transabdominal uterine electromyography. III. MATERIAL AND METHODS

•

•

323 contractions vs. no-contraction events were observed from ten term-pregnant women, all of whom ultimately delivered spontaneously. Uterine EMG was measured non-invasively from the abdominal surface of each patient for 30 minutes. TOCO was used simultaneously to measure uterine contractions. The STM and RMS methods were applied to the uterine EMG data to generate contraction curves similar to TOCO “bellshaped” curves. Correspondence between the raw uterine EMG bursts and the uterine contractions plotted by the various methods was established by looking for temporal overlap of the events. Fifty patients (group 1: labor, n = 24; group 2: ante partum, n = 26) were monitored using transabdominal electrodes. Group 2 was recorded at several gestations. Uterine electrical ‘‘bursts’’ were analyzed by powerspectrum from 0.34 to 1.00 Hz. Average power density spectrum (PDS) peak frequency for each patient was plotted against gestational age, and compared between group 1 and group 2.

A total of 99 patients were grouped as either term (37 weeks or more) or preterm (less than 37 weeks). Uterine

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Uterine Electromyography in Humans – Contractions, Labor, and Delivery

129

electrical activity was recorded for 30 minutes in clinic. EMG "bursts" were evaluated to determine the PDS. Measurement-to-delivery time was compared with the average power density spectrum's peak frequency. Receiver operating characteristic (ROC) curve analysis was performed for 48, 24, 12, and 8 hours from term delivery, and 6, 4, 2, and 1 day(s) from preterm delivery. IV. RESULTS Kappa inter-rater agreement was excellent (0.823) between EMG, TOCO, RMS and STM. Significant correlation was found between all plots. There was no significant difference in the percentage of burst/contraction events plotted by EMG, RMS, and STM compared to TOCO (Fig. 1 EMG: 114.32 ± 18.86 %; OCO: 100.00 ± 0.00 %; MS: 109.18 ± 17.05 %; STM: 102.73 ± 8.31 %). To Group 1 was significantly higher than group 2 for gestational age (39.87±1.08 vs. 32.96±4.26 weeks) and average PDS peak frequency (Fig. 2 - 0.51±0.10 vs. 0.40±0.03 Hz). The power density spectrum peak frequency increased as the measurement-to-delivery interval decreased. ROC curve analysis gave high positive and negative predictive values for both term and preterm delivery (Table 1).

Fig. 2 At term, the average PDS peak frequency was significantly higher for the 24-or-fewer-hours-to-delivery group than for the more-than-24-hours-to-delivery group, whereas at preterm, the average PDS peak frequency was significantly higher in the 4-or-fewer-days-to-delivery group than in the more-than-4-days-to-delivery group (Fig. 3).

Table 1 Labor

PPV

NPV

SENS

SPEC

GS

P

Term

.854

.889

.918

.625

1 day

< 0.01

Preterm

.857

.886

.600

.969

4 days

< 0.01

Fig. 1

Fig. 3

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V. CONCLUSIONS Uterine EMG bursts correspond strongly to TOCO contraction plots. EMG-generated contraction plots (using RMS or STM) are statistically indistinguishable from TOCO contraction plots. So, for pregnant patients exhibiting myometrial activity, uterine EMG could be used in place of TOCO in the clinic for plotting contractions. Uterine EMG in antepartum patients is significantly lower than in laboring patients delivering 66 & trig>1 & af=no & acoag=no → class=thr The first of the selected contrast sets is intuitive to interpret since both primary factors are treatments for cardiovascular disorders. The supporting factors for this set are shown in Table 1. We can see that the supporting factors (including two primary factors) for this contrast set are all about cardiovascular disorders and therefore they substantiate the original interpretation. It is therefore legitimate to say that embolic stroke patients are patients with cardiovascular disorders while cardiovascular disorders are not characteristic for thrombolic stroke patients. Table 1 Supporting factors for contrast set 1

V. CONCLUSIONS We have generalized the notion of supporting factor form subgroup discovery to contrast set mining. We have applied the proposed methodology of supporting factors for contrast set mining in the analysis of the brain ischemia domain and have achieved interpretable and useful contrast set. The experiments show how much benefit can be gained from such in depth analysis. The presented approach to the detection of supporting factors enables in depth analysis. This approach nicely supplements contrast set mining and can be also easily implemented in domains with a very large number of attributes (e.g. gene expression domains).

REFERENCES 1.

CS1

thrombolic

embolic

fo high

0.82

0.73

0.76

af = yes

80%

13%

53%

ahyp = yes

100%

81%

70%

aarrh = yes

100%

19%

45%

Table 2

factors and help the interpretation to move from speculation toward legitimate conclusions.

Supporting factors for contrast set 2 CS2

embolic

thrombolic

age high

74.2

69.85

69.29

chol high

6.30

5.69

6.59

fibr high

5.25

4.51

4.85

fo low

0.64

0.76

0.73

af = no

100%

47%

88%

smoke = no

73%

46%

55%

The second selected contrast set is vague and is not directly connected with medical knowledge. High age and triglyceride values are characteristic for thrombolic stroke, but the boundary values in the contrast set are not high. The rest of the features in this contrast set say no atrial fibrillation and no anticoagulant therapy: again nothing specific. The supporting factors for this set are shown in Table 2. The supporting factors include high cholesterol and fibrinogen, low fundus ocular and non smoker. These patients are old and they do not have cardiovascular disorders. These examples indicate how supporting factors enforce the primary

S. Wrobel (1997) An algorithm for multi-relational discovery of subgroups. In Proc. of the First European Conference on Principles of Data Mining and Knowledge Discovery, 1997, pp. 78–87, Springer 2. Bay S D, Pazzani M J (2001) Detecting group differences: Mining contrast sets. Data Min. Knowl. Discov., 5(3):213– 246, 2001. 3. Dong G, Li J (1999) Efficient Mining of Emerging Patterns: Discovering Trends and Differences. In Proc. of the fifth ACM SIGKDD international conference on Knowledge discovery and data mining, 1999, pp 43-52 4. Quinlan J R (1993) C4.5: Programs for Machine Learning, Morgan Kaufman Publishers Inc 5. Clark P, Niblett T (1989) The CN2 induction algorithm. Machine Learning, 3(4):261–283, 1989. 6. Gamberger D, Lavrac Nada, Krstacic G (2003) Active subgroup mining: a case study in coronary heart disease risk group detection. Artif. intell. med.. [Print ed.], 2003, vol. 28, pp. 27-57. 7. Kralj P, Lavrac N, Gramberger D, Krstacic A (2007) Contrast Set Mining through Subgroup Discovery: Applied to Brain Ischaemina Data. In proc. of the11th Pacific-Asia Conference on Knowledge Discovery and Data Mining, 2007, in press. 8. Victor M, Ropper A H (2001) Cerebrovascular disease. In Adams and Victor's Principles of Neurology, 2001, pp. 821924 9. Fürnkranz J (2001) Round robin rule learning. In Proc. of the 18th International Conference on Machine Learning, 2001, pp 146-153 10. Demsar J, Zupan B, Leban G (2004) Orange: From Experimental Machine Learning to Interactive Data Mining, White Paper (www.ailab.si/orange), Faculty of Computer and Information Science, University of Ljubljana.

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Supporting Factors to Improve the Explanatory Potential of Contrast Set Mining: Analyzing Brain Ischaemia Data 11. Kavsek B, Lavrac N (2006) APRIORI-SD: Adapting association rule learning to subgroup discovery. Appl. artif. intell., 2006, pp.543-583 12. Gamberger D, Lavrac N, Krstacic G (2003) Active subgroup mining: a case study in coronary heart disease risk group detection. Artif. intell. med., 28:27-57 13. Lowry R (2007) Concepts and applications of inferential statistics. http://faculty.vassar.edu/lowry/webtext.html

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14. Lavrac N, Cestnik B, Gamberger D, Flach P (2004) Decision support through subgroup discovery: three case studies and the lessons learned. Mach. learn. [Print ed.], 2004, vol. 57, pp. 115-143. Author: Institute: Street: City: Country: Email:

Petra Kralj Jozef Stefan Institute Jamova 39 1000 Ljubljana Slovenia [email protected]

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A simple DAQ-card based bioimpedance measurement system T. Zagar1 and D. Krizaj1 1

Faculty of electrical engineering, Laboratory for bioelectromagnetics, University of Ljubljana, Slovenia

Abstract— A custom made DAQ-card based bioimpedance measurement system is presented. The signals are processed by the digital lock-in technique. The system was tested on an electrical model of skin with underlying tissues over a frequency range of 20 Hz to 1 MHz. The measurements performed directly with the DAQ-card are compared to the measurements with the instrumentation amplifier interface. The highest achieved accuracy without special calibration and compensation is about 0.5 % for the impedance magnitude and 0.02° for the impedance phase angle in the low frequency region, whereas in the high frequency region the respective values are approximately 1 % and 1°.

In this paper a design of a single channel multi frequency impedance measuring device based on the digital lock-in and the undersampling is described. The presented design is conceptually nothing new, however, the aim of the study is to present a custom made bioimpedance measuring system utilizing the devices that can be found more often than not in every laboratory and to evaluate its accuracy on a simple electrical model of skin.

Keywords— bioimpedance, electrical model, lock-in technique, measurement system

A. Employed hardware

I. INTRODUCTION There are various impedance measurement devices to choose from when measuring bioimpedance, however, some of the commercially available equipment is not suitable for direct measurement on biological samples [1]. Additionally, most of the bioimpedance measuring devices in the market are designed for specific purpose and can hardly be used for some experiments, therefore a need to design a custom device arises. Moreover, for many basic laboratory experiments there is no need to use a high-tech maximal accuracy bioimpedance measuring device – often a custom made solutions are even better suited in terms of their flexibility and adaptability to specific requirements of the problem. Electrical impedance is by definition a ratio of alternating voltage and current expressed mathematically in the complex notation, however, despite the apparent simplicity in definition a variety of methods and approaches exist to measure it. An often used method of bioimpedance measurement is a four-electrode method [2]. The current is injected into the sample through one pair of electrodes and the other pair of electrodes is used to measure the resulting voltage drop. If no current flows through the voltage measurement electrodes there is also no voltage drop across these electrodes and the measured voltage is the same as the voltage under the electrodes. Further, the devices usually employ some sort of demodulation method to measure the amplitude and the phase of a signal, which is nowadays mostly done by digital signal processing.

II. MEASUREMENT SYSTEM OVERVIEW

No application specific hardware was designed for this study. The voltage was measured directly by the USB DAQ card (NI-USB6211) and the current was also measured by the DAQ card as a voltage drop on a resistor R of a nominal value 47 Ω (Fig. 1). This two voltage measuring channels were configured to operate in a differential mode. The excitation voltage was set to a fixed value of 1.25 V and generated by an Agilent 33220A signal generator. The frequency of the generator was controlled trough the USB link with a personal computer. B. Digital lock-in technique Lock-in amplifies are commonly used to detect minute signals buried in noise [3]. The principle of the lock-in technique is quite straightforward: if the input signal vi is given by (1):

vi = A sin(ωt + ϕ ) + n(t ) ,

(1)

where n(t) is a random (white) noise, the amplitude (A) and the phase angle can be obtained by multiplication with a reference sine and cosine function of the same frequency ( ωr) as the input signal. The output of such multiplication is (2):

A [cos(ϕ ) − cos(2ωr t + ϕ )] + n(t ) sin(ωr t ) 2 (2) A = [sin(ϕ ) + sin(2ωr t + ϕ )] + n(t ) cos(ωr t ) 2

vo sin = vo cos

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 182–185, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

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If the output is averaged over an integer number of periods the result equals (3):

A A cos(ϕ ) + n 2 2

ωr

A A = sin(ϕ ) + n 2 2

ωr

vo sin = vo cos

sin(ϕ n ) ,

(3)

cos(ϕ n )

where An and ϕn are the amplitude and the phase angle of the spectral component of noise n(t) at frequency ωr. A signal has to be sampled over at least one complete period to get the accurate results when averaging, which means that the number of samples (N) satisfies condition (4), where k is an integer (denoting the number of sampled periods), fs is the sampling frequency and f is the frequency of the sampled signal:

N=

kf s . f

(4)

In this case either fs, f, or both of the frequencies, respectively, have to be adjusted to fulfill the condition (4). However, if the number of samples is high enough condition (4) can be violated and the average value of the signal still gets close to its true value. This is the case with presented design where the number of samples was set to 50,000. C. Sampling frequency In the presented system a fixed sampling frequency of 50 kHz was used for the frequencies above 2.5 kHz. A sampling frequency of 1 kHz was used for the frequencies below 2.5 kHz due to an inadequate settling time in the low frequency region when testing the system on the model. The number of samples in this case was set to 2000. D. Electrical model of skin and underlying tissues The system was tested on a simple electrical model of skin with underlying tissues as shown in Fig. 1. The values for the elements were chosen on the basis of previous experience in a way that the impedance of a model when measured at two terminals approximately suits the impedance of the living human skin measured at two terminals. The impedance Ze represents joined

Fig. 1 Measurement system with a simple model of skin and deeper viable tissues

electrode impedance and impedance of stratum corneum. The value for Re2 was set to 10 Ω and suits the absolute value of the impedance obtained with a precision LCR-meter when measuring two Ag/AgCl cup electrodes (cup 8mm in diameter, filled with an electroconductive gel) placed in a direct contact with each other. The value for Re1 was set to 10 kΩ and suits the value [4] obtained after several strippings of stratum corneum. This is also in accordance with [5], where the low-frequency impedance varied from 10 kΩ to 1 MΩ. A value for Ce was chosen to be 10 nF. The impedance Z represents deep viable tissues. The chosen values agree with a fact that the main electrical impedance resides in the stratum corneum while the impedance of the other layers is several orders of magnitude lower [6]. The values were: R1 = R2 = 33 Ω and Cz = 100 nF. III. RESULTS First the impedance Z (marked in Fig. 1) was measured without the Ze impedances and compared to the value obtained with an LCR-meter (Fig. 2).

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T. Zagar and D. Krizaj 0.4

70

0.2

60 70

magnitude, Ω

magnitude error, %

184

0 -0.2

50 40

65 2

-0.4 1 10

2

10

3

4

10 10 frequency, Hz

5

10

30 1 10

6

10

0.2

0

-0.2

-0.4 1 10

3

10 2

10

10 3

4

3

4

10 10 frequency, Hz

5

10

6

10

5 phase angle, °

phase error, °

amplifier ref. value without amp.

2

10

3

4

10 10 frequency, Hz

5

10

6

10

0 -5 -10 -15 -20 1 10

amplifier ref. value without amp. 2

10

10 10 frequency, Hz

Fig. 3 Impedance Z

Fig. 2 Comparison of the impedance Z measured with the DAQ-card to the

5

10

6

10

measured as shown in Fig. 1

measurement with the LCR-meter

To get an accurate value for the impedance phase angle the sampling time between the channels (conversion time) has to be accounted for (Fig. 5). There is another possible source of error in the presented model: from Fig. 1 it can be concluded that there are relatively high common mode voltages present in the system. The voltage difference to be measured is approximately 3 mV (when a voltage of 1 V is applied to the system) and is floating on the voltage of almost 0.5 V, which is about 170times higher. An amplifier with a high common mode rejection is required to amplify this signal successfully. At least in the low-frequency region the CMRR of the used DAQcard is high enough (100 dB from DC to 60 Hz) and should reject the common voltage.

magnitude error, %

3 without amp. amplifier

2 1 0 -1 -2 1 10

2

10

3

4

10 10 frequency, Hz

5

10

6

10

6 phase error, °

There is an offset in the low-frequency region of impedance magnitude, which can be compensated. The phase error from about 100 Hz to 400 Hz is the error of the LCRmeter. In the medium frequency region the error gets higher, however, this is due to the voltage dependant capacitance of the capacitor Cz used in the electrical model: the absolute value of the impedance Z measured with the LCR-meter at 1.0 V and at 0.1 V (rms values) was different by approximately 10 % and the voltage when measuring with the DAQ-card was about 0.08 V (rms) and was not controlled to be set to the same value as with the LCRmeter measurement. Further, the behavior of the designed system when the impedance of the electrodes and the skin is present was tested. The results are shown in Fig. 3. The sampling frequency was set to 50 kHz for the entire frequency span. Quite large discrepancies can be noticed in the low frequency region when measuring directly with a DAQ-card. This is due to an inadequate settling time. When measuring two channels the device has to switch a multiplexer, usually made of switched capacitors. The settling time of the channel increases if the source impedance is high. The medium frequency region follows the reference value rather well (the reference value was the value of the impedance Z measured without the Ze impedances directly with a DAQ-card, c.f. Fig. 2). In addition, Fig. 4 shows the resulting error when the sampling frequency was set as described in the sampling frequency section (II C). In this case the low-frequency error when measuring directly with a DAQ-card is almost completely vanished.

without amp. amplifier

4 2 0 -2 1 10

2

10

3

4

10 10 frequency, Hz

5

10

6

10

Fig. 4 Comparison of the reference value for the impedance Z to the measurement with an instrumentation amplifier interface and to the measurement performed directly with a DAQ-card

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100

IV. CONCLUSIONS

50

phase angle, °

0

-50

-100

-150

-200 1 10

2

10

3

4

10 10 frequency, Hz

5

10

6

10

This paper shows that it is possible to achieve a reasonable accuracy in bioimpedance measurement with a very simple setup despite the severe measurement conditions demonstrated in the electrical model. It has to be notified that absolutely no calibration procedure was performed and still the results were satisfactory, however, a calibration should be performed for the reliable measurements. Moreover, to increase the accuracy especially in the high frequency region some sort of compensation is necessary. When measuring with a specific type of DAQ-card a special attention should be paid to assure adequate settling time for the measured signals.

Fig. 5 Phase angle of the impedance Z if a delay between the channels is

REFERENCES

not taken into account

To lower the source impedance of the voltage measured by channel 1 (c.f. Fig. 1) and improve the performance of the system an instrumentation amplifier interface between the model and the DAQ-card was used (Fig. 3, solid line). A similar solution to improve the measurement accuracy was proposed by [7]. A high speed FET-input instrumentation amplifier (INA111) was employed with a gain set to about 10. The amplifier gain/phase characteristics were recorded for the treated frequency span and taken into account when calculating the impedance. The results in the low frequency region were significantly improved (the achieved accuracy is about 0.5 % and 0.1° for the impedance magnitude and the phase angle, respectively), however, the error in the high frequency region gets larger (about 2.5 % for the impedance magnitude and 4° for the impedance phase angle). In comparison to the measurement performed directly with the DAQ-card the results obtained with an amplifier interface were slightly better in the low-frequency region and worse in the high frequency region, where the accuracy of a direct measurement was about 1 % and 1° for the impedance magnitude and phase angle, respectively.

1. 2. 3. 4. 5. 6. 7.

Dudykevych T, Gersing E, Thiel F et al (2001) Impedance analyser module for EIT and spectroscopy using undersampling. Physiol Meas 22 (1):19-24 Geddes LA (1996) Who introduced the tetrapolar method for measuring resistance and impedance? IEEE Eng Med Biol 15 (5):133-134 Grimnes S and Martinsen O G (2000) Bioimpedance and Bioelectricity Basics Academic Press. pp. 188 ISBN 0-12-303260-1 Yamamoto T, Yamamoto Y (1976) Electrical-properties of epidermal stratum-corneum. Med Biol Eng 14 (2):151-158 Rosell J, Colominas J, Riu P et al (1988) Skin impedance from 1 Hz to 1 MHz. IEEE T Bio-Med Eng 35 (8):649-651 Pliquett F, Pliquett U (1996) Passive electrical properties of human stratum corneum in vitro depending on time after separation. Biophys Chem 58 (1-2):205-210 Gersing E (1991) Measurement of electrical-impedance in organs measuring equipment for research and clinical-applications. Biomed Tech 36 (1-2):6-11 Author: Tomaz Zagar Institute: Street: City: Country: Email:

University of Ljubljana, Faculty of electrical engineering Trzaska cesta 25 Ljubljana Slovenia [email protected]

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Benefits and disadvantages of impedance-ratio measuring method in new generation of apex-locators T. Marjanovic1, Z. Stare1 1

Faculty of Electrical Engineering and Computing, Department of Electronic Systems and Information Processing, Zagreb, Croatia

Abstract— One of the most critical procedures for a successful endodontic treatment is determination of root canal length. Electronic devices called apex-locators have been used for working length measurement for more than forty years. First apex-locators used direct current, but had many drawbacks. In order to improve the measurement procedure, direct current was replaced by alternating current and impedance was measured on single frequency in order to calculate the position of apical constriction. Problems with single frequency apex-locators occurred due to the presence of electrolytes in the canal. Thus, new generation of locators has been introduced – impedance is now measured on two frequencies and the position of apical constriction is calculated from corresponding impedance ratio. The aim of this paper is to examine properties of the impedance-ratio method and to compare it with single frequency measurements. Experiment was carried out in-vitro. Exact position of apical foramen on each tooth was measured with microscope. Then the teeth were placed in a freshly mixed alginate, commonly used in such measurements. Impedances were measured on frequencies commonly used by apex-locators, and with Kerr file positioned at apical foramen at several positions above and under it (in steps of 0.25 mm). Measurements were performed in dry canal and in canal filled with electrolytes usually used in endodontic treatment. Sensitivity on different type of electrolytes and sensitivity on electrode displacement were calculated for single frequency and frequency-ratio technique in order to investigate the benefits of each. By comparing them with calculated variation coefficient of raw measurements we concluded that the frequency-ratio method (used in new generation of apex-locators) is more robust to electrolytes, but its sensitivity decreases in normal condition of the dry canal. For achieving full credibility of imposed conclusion, in-vivo verification should also be performed.

constriction (also called minor foramen) is the narrowest part of root canal, 0.5 to 0.8 mm from the apical foramen (major foramen), depending on tooth type and age [1]. The apical constriction, also described as the cementodentinal junction, is the anatomical and histological landmark where the periodontal ligament begins and the pulp ends. It represents a potential natural barrier between the contents of the canal and the apical tissues (Schilder 1967) and it is generally accepted that the preparation and obturation of the root canal should be at, or short of, the apical constriction. The success of the whole treatment depends on the accuracy in determining the position of apical constriction. Today, the only known accurate way of determining it is to perform measurement after the tooth extraction. Therefore research and improvement of measuring methods is highly desirable. The most common way of root canal length determination is by using electronic methods. Many studies report on the accuracy achieved by the new generation of electronic apex-locators as well as their extended measurement capabilities in the presence of electrolytes (Fouad et al. 1993, Frank & Torabinejad 1993, Mayeda et al. 1993, Kobayashi 1995). Moreover, it is known that radiographic methods of apical constriction determination are less accurate than the electronic method (Stein & Corcoran 1992) while apical constriction is often short of anatomical apex of tooth (seen in radiograph) [1]. Electronic apex-locators work on the principle of bioimpedance measurement on one or more frequencies. One (neutral) electrode is placed on oral mucosa and the

Keywords— root canal length, electronic apex locator, impedance-ratio measuring method, electrolytes in endodontic, electrode displacement sensitivity

I. INTRODUCTION The success of endodontic treatment depends on the cleaning of root canal. The removal of all pulp tissue, necrotic material and microorganisms from the root canal requires minimal disturbance of the surrounding tissue. The apical foramen is not always located at the anatomical tooth apex (Fig. 1) and that distance can be up to 3 mm. Apical

Fig. 1 Apical anatomy

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 206–209, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Benefits and disadvantages of impedance-ratio measuring method in new generation of apex-locators

other (active) electrode is connected to inter–canal instrument, like Kerr file, which is moved along the root canal. The impedance between the electrodes is measured and then the distance from the apical constriction is calculated. For better accuracy, significant change of impedance, used for calculation, is required when the position of Kerr file in root canal changes. On the other side, minimum influence on impedance with different teeth and lower dependency on electrolyte presence is needed. Measurement method that used bioimpedance on single frequency worked well with dry canal, but is less accurate) when commonly used agents in therapy, blood or saliva are present in the canal. For this reason, impedance-ratio method and new generation of apex-locators have been introduced. Impedance sensitivity and impedance-ratio values on electrode displacement near the apical foramen are elaborated in this paper, as well as the influence of commonly used agents and variation with different teeth. II. MATERIALS AND METHODS Measurement is performed in-vitro on twenty singlerooted teeth placed in a freshly-mixed alginate dental impression material, commonly used as a physical model for apex-locator evaluation [2, 3, 4, 5]. A simple mounting model with micrometer has been built for precise and consistent measurement. A large-area neutral electrode made of stainless steel is placed into the alginate and for active, measuring electrode, a Kerr file K-10 or K-15 is used, depending on which fits better into the foramen. Displacement of Kerr file tip from the apical foramen is controlled with micrometer. A Hewlett Packard HP4284A precise RLC meter is used for impedance measurement. Measurement and data storage are computer-controlled and both, real and imaginary part of impedance are logged on several frequencies in the range from 100 Hz to 1 MHz. Measurement range includes frequencies of 400 Hz and 8 kHz which are used by the majority of apex-locators (Root ZX for instance) and elaborated into detail in this paper. Teeth are kept in saline solution until the experiment. The position of apical foramen is precisely determined with microscope and then each tooth is placed in a freshly mixed alginate. Once the canal has been dried with paper points, the measurement of root canal impedance is performed in the range from 2 mm above the apical foramen to 0.5 mm under the apical foramen in steps of 0.25 mm. During the measurement a hysteresis is noticed, so the measurements are taken only when the file has scrolled down. Measurements are repeated for the canal moisten with saline solution and for the canal filled with 2.5% sodium

207

hypochlorite solution and calcinase, commonly used in endodontic treatment. For quantitative comparison of measuring methods, we have introduced the following parameters: sensitivity factors, coefficient of variation and estimated variability of position. The sensitivity factor of impedance S|Z| is defined as the relative impedance change ΔZ/Z on a single frequency with file-tip displacement:

SZ =

ΔZ Z . Δd

(1)

If we define impedance ratio rZ = Z(400 Hz) / Z(8 kHz), then the sensitivity factor of impedance-ratio Sr is defined as the relative change in impedance ratio ΔrZ/rZ with displacement Δd:

Sr =

ΔrZ r Z . Δd

(2)

The coefficient of variation cv is defined as the ratio of the standard deviation σ to the mean µ:

cv =

σ μ

.

(3)

For the purpose of rough estimation of variability in measured position, we define an estimated variability of position Δl for both, single frequency and impedance–ratio, methods as:

Δl =

cv . S

(4)

III. RESULTS AND DISCUSSION Frequency dependence of impedance magnitude differs significantly for each tooth, but they all track a similar curvature. For comparison purposes, impedances are normalized and results for clinically important file displacement of the apical foramen are plotted on Fig. 2 to 4. The majority of single frequency apex-locators work on 1 kHz or around this frequency. It is obvious that they have great sensitivity [6] in normal clinical condition of a dry canal when file approaches apical foramen (Fig. 2 to 4) – relative change in magnitude of impedance when moving file-tip is 92 %/mm. But in the situation when the canal is not sufficiently dried immediately before taking

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dried canal wet canal hypochlorite calcinase

0,75

0,50

0,25

0,00 100

1000

10000 Frequency [Hz]

100000

1000000

0,75

dried canal wet canal

0,50

hypochlorite calcinase

0,25 0,00

Normalised impedance

1,00

Fig. 2 Influence of canal filling, 1.0mm above apical foramen

100

1000

10000 Frequency [Hz]

100000

1000000

1,00

5,00

Fig. 3 Influence of canal filling; 0.5mm above apical foramen

dried canal wet canal hypochlorite calcinase

1,00

Normalised impedance 0,25 0,50 0,75 0,00

measurement, problems can occur – relative change in magnitude of impedance when moving file-tip drops to around 30 %/mm on 1 kHz, depending on type and amount of moisture; as presented later in Table 1. Two widely accepted approaches exist in case of two or more frequency apex-locators [1, 7]: voltage difference and impedance ratio method. Voltage difference method uses absolute difference of impedance on two frequencies (which incorporates the information on presence of the electrolyte). The sensitivity of impedance change with file-tip displacement remains the same as in already discussed case of single-frequency measurement. In case of ratio method apex-locators, the impedance ratio on two frequencies represents the position of the file in root canal and it is required that this ratio significantly depends on file-tip displacement, but not on the presence of electrolytes in the canal and on the type of a tooth. The majority of instruments that use this method (widespread Root ZX for example) take measurements on frequencies of 400 Hz and 8 kHz. The ratio on these frequencies is analyzed here. Impedance–ratio shows significantly less change in moistened canal (Fig. 5) than in a dry canal, but generally lower relative sensitivity to file displacement of apical foramen can also be noticed (about 60 %/mm, Table 1). Except for decreased sensitivity of impedance–ratio method, measurement on different teeth showed even higher variation coefficient of impedance–ratio than is the variation coefficient of impedance on a single frequency. With an estimated variability of position Δl defined as in (4) and according to Table 1, we can conclude that single frequency method gives best results when measurement is performed in normal conditions of dry root canal. However, ratio method is more accurate if root canal is moistened.

100

1000

10000 Frequency [Hz]

100000

1000000

Fig. 4 Influence of canal filling; file at apical foramen

dried canal wet canal hypochlorite calcinase

Impedance ratio 2,00 3,00 4,00

Normalized impedance

1,00

0,50

0,00 -0,50 -1,00 -1,50 -2,00 Displacement of file tip to apical foramen [mm]

Fig. 5 Influence of canal filling on impedance–ratio

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Benefits and disadvantages of impedance-ratio measuring method in new generation of apex-locators

Table 1

impedance ratio

single frequency

parameter

Comparison of measuring methods in presence of electrolyte unit

electrolyte in canal dry

hyp.

calc.

cv , Z

-

0,69

0,51

0,63

SZ

% / mm

92

25

18

Δl Z

mm

0,75

2,04

3,5

cv ,r

-

1,04

1,13

1,17

Sr

% / mm

54

69

74

Δl r

mm

1,92

1,64

1,58

Minimal error (in millimeters) can be expected in single frequency method in case of dry root canal. When electrolyte is present, accuracy of single frequency method drastically decreases. However, if impedance-ratio method is used, better results are achieved when conductive media is present in the canal.

Besides the sensitivity to electrode displacement and variation in measured parameter (impedance or impedanceratio) which cause dispersion in determination of apical foramen position (Δl|Z|, Δlr), a systematic error in measurements can also be noticed when electrolyte is present in the canal. Fig. 5 shows that in case of impedanceratio method, the mean reading of working length is expected to be about 0.3 mm longer than it really is when electrolyte is present. In contrast, if single frequency measurement is used, readings will be shorter with conductive media in the canal (for example –0.5 mm on 5 kHz). The differences between a dry root canal and a canal filled with electrolyte are expected to be much lower in reallife than presented in this paper. Normally, only insufficiently dried (blown) root canal can be expected, and here, for research purposes, canals were filled to the top. Conclusions are made on the basis of physical model and it is necessary to compare them with in-vivo measurements to achieve its full credibility [8].

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dry root canal. Impedance-ratio method has better tolerance to electrolytes in the canal, but it also shows lower accuracy in normal conditions. In real applications root canal is never fully-filled with agents (like in this research) and their lower influence is expected. Thus, if there is no assurance that root canal is dry (canals with perforations, bleeding teeth), impedance-ratio method with the risk of lower accuracy is advisable. Although the accuracy of contemporary apex–locators is sufficient for most cases, situation is not perfect and further elaborations of single frequency methods, as well as new measuring methods developments are encouraged. For the credibility of drawn conclusions, further research and in-vivo verification is required.

REFERENCES 1. 2.

3. 4. 5. 6.

7.

8.

Gordon MP, Chandler NP. (2004) Electronic apex locators. Int Endod J 7(7): 425-7 Jenkins JA, Walker War , Schindler WG, Flores CM. (2001) An in vitro evaluation of the accuracy of the root ZX in the presence of various irrigants. J Endod. 27:209–11 DOI 10.1097/00004770-200103000-00018 Kaufman AY, Keila S, Yoshpe M. (2002) Accuracy of a new apex locator: an in vitro study. Int Endod J. 35:186–92 DOI 10.1046/j.1365-2591.2002.00468.x A. Y. Kaufman, S. Keila & M. Yoshpe (2002) Accuracy of a new apex locator: an in vitro study. Blackwell Int End J 35:186–192 A. ElAyouti & C. Löst (2006) A simple mounting model for consistent determination of the accuracy and repeatability of apex locators. Int Endod J 39: 108–112 Z. Stare, T. Protulipac (2003) Sensitivity of the Root Canal Impedance to Electrode Displacement – in vivo and in vitro Measurement, MEASUREMENT Proc. of the 4th Int. Conf., Smolenice, Slovak Republic, 2003, pp 230–233 K. C. Nam, S. C. Kim, S. J. Lee et al. (1991) Root canal length measurement in teeth with electrolyte compensation. Med and Biol Eng and Comp, 40(2):200-204 DOI 10.1007/BF02348125 Stare Z, Lacković I, Galić N (2001) Evaluation of an in vitro model of electronic root canal measurement, Proc. of the 9th Mediterranean Conf. on Med. and Biolog. Eng. and Comput., Pula, Croatia, 2001. pp: 1047–50

IV. CONCLUSION Two measuring methods are compared in this paper: absolute impedance and impedance-ratio methods. For the purpose of quantitative comparison, quality factors were introduced and accordingly it has been concluded that single-frequency method gives best results in conditions of

Author: Institute: Street: City: Country: Email:

Tihomir Marjanovic Faculty of Electrical Engineering and Computing Unska 3 Zagreb Croatia [email protected]

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Bioimpedance spectroscopy of human blood at low frequency using coplanar microelectrodes J. Prado, M. Nadi, C. Margo and A Rouane Laboratoire d’Instrumentation Electronique Nancy (LIEN), Nancy University, France. Abstract— Dielectric properties of biological substances are usually deduced ex vivo by the way of the impedance measurement of a cell loaded by the investigated medium. At low frequency it is well known that the bioimpedance depends on the polarization effects that occur at the electrodes interface. Measurements being affected for frequencies lower than 50 kHz for standard electrodes, black platinum was used to decrease polarization effects. In this paper, dielectric properties of blood measured at different temperatures are presented for frequencies varying between 100 Hz and 1 MHz. Keywords— bioimpedance spectroscopy, microelectrodes, polarisation effect, dielectric properties, blood

I. INTRODUCTION Impedance Spectroscopy of biological tissues has been previously inestigated as a technique for non invasive assessment of tissue characterisation [1]. Measurement of dielectric properties may be deduced from the bioimpedance measurement obtained by the interaction between an electromagnetic field source and a biological sample. In the frequency range up to 10 MHz, current conduction through tissue is mainly determined by the tissue structure, i.e. the extra- and intra-cellular compartments and the insulating cell membranes. Therefore, changes in the extra- and intracellular fluid volumes are reflected in the impedance spectra [2]. Different electrodes configurations are used to measure bioelectric phenomenon. One can distinguish between two basic functional types, macroscopic or microscopic measurement. Electrodes for macroscopic characterisation consist in bioimpedance measurement of a biological tissue sample or organ. Electrodes for microscopic characterisation were more recently [3] used for bioimpedance measurement of biological cell or very small cells aggregate. Microscopic electrodes may be used to characterize extracellular and intracellular fluids, or cell membrane. In this paper we are dealing with biological cell scale with the goal of optimizing the interface between electrodes and biological cells agregate at low frequency. The contact of the electrodes with the biological tissue or the electrolyte leads to electrochemical phenomena. This results in a charge distribution in the immediate vicinity of the electrodes and thus in an additional impedance called

“polarization impedance” [4]. This well known phenomena is specific for a given electrode-electrolyte interface. The potential due to the polarisation impedance is dependent upon he metal-electrolyte combination, current density, and frequency [5]. Since water is the primary constituent of both in vivo and vitro fluids, it is generally assumed that electrode interface impedance in these fluids is similar to that observed for physiological serum. Considerable data describing the impedance at the electrodes-solution interface are available [6]. In therapeutic or diagnostic applications or in studies on biological effects of the electromagnetic radiations, dosimetric evaluations are greatly affected by the precision of dielectrics parameters values of biological tissues. These parameters are sensitive to many influencing factors like temperature of the target organ. However, these effects remain misunderstood and the measured values are sparse, at various frequencies and exist only for some organs as compiled in [7]. II. MATERIAL AND METHODS Many methods and techniques for the measurement of complex impedance exist and are described in the litterature. In this work, the auto balancing bridge technique associated to a microsensor based on a multielectrodes matrix was applied to determine the frequential variation of a complex impedance. In the present study, we intented to measure the dielectric properties of blood for a frequency range between 100 Hz and 1 MHz in order to complete previous work at higher frequencies [8]. A. The microsensor The microsensor consists of an array of sixteen platinum microelectrodes for measurement with two reference microelectrodes on its surface. That kind of geometry has been employed previously for neural activity recording or stimulation [9], [10], [11]. We have adapted it (Figure 1) for impedance measurements of solutions. Thus, new design strategies had to be considered in order to optimize the probe performances for bio-impedance measurements at low frequencies [13].

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 186–189, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Bioimpedance spectroscopy of human blood at low frequency using coplanar microelectrodes

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a PC (Figure 2). Data acquisition and analysis were managed using HPVEE© software. III. RESULTS C. Characterization of the sensor

Figure 1: view of the sensor with its tank The microelectrodes matrix consists of an eighteen microelectrodes (2-ground reference, 2 sets of 8 active electrodes) placed on a plate of substrate glass (1 x 1.2cm). This configuration provides the advantage of an easy fabrication by using standard microelectronic technologies which implies high reliability, low costs and the possibility to integrate other sensors and electronics on the same probe. The active microelectrodes are squares with dimensions of 100x100µm and 180 nm thickness. Microelectrodes reference are rectangular with 1x2.5mm of surface and 180nm thickness. This cell measurement was produced at the Centro Nacional de Microelectronica (CNM-University of Barcelona). The technological process consists in two photolithographic steps starting from a thermal oxydation to grow a thick field layer (800 nm) on 4-in. (~10 cm) P-type ‹100› Si wafers with a nominal thickness of 525 µm and is presented in [8]. B. Electronic Instrumentation The basic measurement system, based on an impedancemeter to which a microsensor is connected, is not described here in details. This sensor is a measurement cell including a Plexiglas tank for the solution under test, the electronic card for data acquisition, the impedancemeter and

S en so r

D a t a a cq u i si tio n electro n ic bo a rd

The bioimpedance depends on the frequency and the polarization effects that occur at low frequency. In this paper, dielectric properties of physiological serum are determined by a monopolar system. The polarization resistance and capacitance of electrodes in contact with standard solutions (Potassium chloride) has been investigated. A set of measurements were made at 37°±0.5°C from 100 Hz to 1 MHz range using a commercial impedancemeter. The measurement microsensor has coplanar platinum electrodes square of 100µm x 180 nm in height, the applied voltage level being 25mV. Electrolyte solution of known conductivity was used to characterize the measurement cell. A theoretical model of the impedance has been calculated using finite elements method (FEM) for each electrode. The numerical simulation was used to determine the cell factor of the microelectrodes. Effects of the polarization on the measured impedance and the dielectric characteristics were also investigated. Measurements are affected for frequencies lower than 50 kHz for standard electrodes in Platinum. This limit due to the polarisation impedance decreases to 10 kHz when, as it is well known, black platinum is used [14]. D. Measurement of blood electrical properties Measurements were done using standard Platinum electrodes and electrodes covered by black Platinum for both satndard solutions, animal and human bloods. We present here, as an example, only the relative permittivity and the electric conductivity obtained for human blood at different temperatures between 100 Hz and 1 MHz using microelectrodes covered by black platinum (Figure 3).

I m p éd a n cem eter

PC

Figure 2: View of the sensor and its electronic conditionning

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1,2

100000000 10000000

1

εr

1000000

εr

0,6

10000 1000

0,4

σ

100

σ (S/m)

0,8

100000

0,2

10 1

0 0,1

1

10

100

1000

Fréquence (kHz) εr 25°C

εr 37°C

εr 42°C

σ 25°C

Figure 3: Electric properties of human blood with platinum IV. DISCUSSION AND CONCLUSION For the impedance obtained with the microelectrodes covered with a black platinum layer, approximately 50% of the polarization effects was eliminated for frequencies greater than 10 kHz. But for frequencies lower than 10 kHz the electrode electrolyte interface influenced clearly the measurement of the bioimpedance. These results have shown that the measurement cell may be characterized by determining the conductivity of a dielectric properties with less than 20% error for a frequency over 10kHz when the microelectrodes are covered by black platinum. The conductivity has an error mainly due to the temperature effects, the electrode/electrolyte impedance, electrodes geometry of the measurement cell. The imaginary part of the complex impedance is strongly influenced by the parasitic capacitances at the microelectrodes interface and thus the permittivity at these frequencies remains to high and difficult to measure. The measurement cell was used for a small sample of blood in this first step with only one active electrode and a reference electrode. The next step will be to develop comparative measurements between single cells using a multielectrodes configuration since there is no interaction or cross-talk between the micro-electrodes. The use of microelectrodes opens up new areas in biomedical applications. Using microelectrodes arrays, it

σ 37°C

σ 42°C

covered by Pt-noir

should be possible to monitor cell movement or characterise dielectric properties of biological cell. Understanding their electromagnetic behaviour, the nonlinear phenomena or analyzing electromagnetic properties of an isolated cell versus an aggregate of cells [15], are a few examples of benefits that bioimpedance spectroscopy applications will offer from miniaturization in the near future.

ACKNOWLEDGMENT We thank the Centro Nacional de Microelectronica (CNM) for the fabrication of the measurement cell and PhD. Antoni Ivorra and M.S. Rodrigo Gomez from Barcelona University for their help and advices.

REFERENCES 1. 2. 3.

4.

Schwan H P 1963 Determination of biological impedances - Chapter 6 Physical techniques in biological research 6 Academic press Foster K R and Schwan H P 1996 Dielectric properties of tissues Chapter 1 Handbook of Biological Effects of Electromagnetic Fields 2ème edition Ed :Polk C. et Postow E CRC Press 27-102 Gomez R, Bashir R, Sarikaya A, Ladish M R, Sturgis J, Robinson JP, Geng T, Bhunia A K, Apple HL and Werely S 2001 Microfluidic Biochip for Impedance Spectroscopy of Biological Species Biomedical Microdevices 3:3 201-209 Fricke H 1932 The theory of electrolytic polarisation Phil. Mag. 14 310-318

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Bioimpedance spectroscopy of human blood at low frequency using coplanar microelectrodes 5.

Schwan H P 1966 Alternating current electrode polarisation Biophysik 3 181-201 6. Grimnes S and Martinsen O G 2000 Bioimpedance and Bioelectricity basics Academic Press. 7. Gabriel C., Gabriel S and Corhout E (1996a), “ The dielectric properties of biological tissues:I. Literature survey ”, Phys. Med. Biol., vol 41 pp 2231–49. 8. Jaspard F and Nadi M 2002 Dielectric properties of blood: an investigation of temperature dependence, Physiol. Meas. 23 547-554 9. Ivorra A, Gomez R, Noguera N, Villa R, Sola A, Palacios L, Hotter G and Aguilo J 2003 Minimally invasive silicon probe for electrical impedance measurements in small animals Biosensors Bioelectron. 19 391–9 10. Borkholder DA, Bao J, Maluf NI, Perl ER and Kovacs GT 1997 Microelectrode arrays for stimulation of neural slice preparations J Neurosci Methods 77 61-66 11. Kovacs G T A, Storment C W and Rosen J M 1992 Regeneration Microelectrode Array for Peripheral Nerve Recording and Stimulation IEEE Trans. Biomed. Eng. 39 893-902

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12. Ackmann J J and Seitz M A 1984 Methods of complex impedance measurements in biologic tissue CRC Crit. Rev. Biomed. Eng. 11 281-311. 13. Markx G H and Davey C L 1999 The dielectric properties of biological cells at radiofrequencies Applications in biotechnology Enzyme and Microbial Technology 25 161-171 14. Mcadams ET and Jossinet J 1991 Electrode-electrolyte impedance and polarisation Innov. Tech. Biol. Med. 12 11-20 15. Pavlin M, Miklavcic D. Effective conductivity of a suspension of permeabilized cells: a theoretical analysis. Biophys. J. 85: 719-729, 2003. NADI Mustapha Electronic Instrumentation Laboratory of Nancy Nancy University BP 239, Bd des Aiguillettes 54506, Vandoeuvre les Nancy France [email protected]

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Dielectric properties of water and blood samples with glucose at different concentrations A. Tura1,, S. Sbrignadello1, S. Barison2, S. Conti3, G. Pacini1 1

ISIB-CNR, Padova, Italy, 2 IENI-CNR, Padova, Italy, 3 BC Dynamics, Milan, Italy

Abstract - Impedance spectroscopy has been proposed as possible approach for non-invasive glycaemia monitoring. However, few quantitative data are reported about impedance variations related to glucose concentration variations, especially below the MHz band. Furthermore, it is not clear whether glucose directly affects the impedance parameters or only indirectly by inducing biochemical phenomena. We investigated the impedance variations in glucose-water and glucose-blood samples, for increasing glucose values (up to 300 mg/dl). In all the frequency range (0.1–107 Hz) glucose-water samples showed huge impedance modulus increases for increasing glucose values (up to 135%). In blood the impedance modulus showed only slight variations (2%), but again in a wide frequency range. Therefore: i) glucose directly affects the impedance parameters of solutions; ii) the influence on the impedance seems to decrease in high conductivity solutions, but it is still clearly present. Keywords - Impedance spectroscopy, glycaemia, diabetes, monitoring, non-invasive

I. INTRODUCTION In recent years the measurement of tissue and blood impedance through an alternating current has been suggested as a non-invasive approach to determine glycaemia [1]. In [2], it was shown that variations in blood glucose concentration determine significant changes in the impedance of a subject’s skin and underlying tissues in a range between 1 and 200 MHz. However, the authors claimed that the observed impedance changes were not due directly to glucose but to biochemical reactions triggered by variations of glucose concentration, which cause variations in the electrolyte balance across the membrane of erythrocytes. In other studies, however, impedance variations were found in glucose-water solutions with different glucose concentrations, despite no cell component was present. This was observed even at glucose concentration values that mimic glycaemic levels in human blood [3]. On the other hand, in [3] the impedance differences were observed only in a relatively narrow frequency range. These partially contradictory results show that it is not completely clear whether glucose directly affects the impedance behavior of a solution, especially when

physiological concentration levels are considered. The aim of this study was to examine possible impedance variations in solutions at different glucose concentrations within the physiological range. We studied glucose solutions both in pure water and in blood in an in vitro context. Special attention was devoted to the analysis of low frequencies, which were poorly investigated in previous studies, especially in blood. II. MATERIALS AND METHODS A. Preparation of samples A sample of deionized water (18.5 MΩ · cm resistivity, Millipore MilliQ Element system, Billerica MA, USA) was prepared. The same water was used to prepare three glucose-water samples, at glucose concentrations spanning from normal glycaemia to that observed in severe diabetes, i.e. 100, 200, 300 mg/dl. Each sample consisted of 50 ml of water. D-glucose (99.5%, Fluka) was added to the water samples to reach the indicated concentrations. For the preparation of blood samples we collected 500 ml of bovine blood immediately after the animal slaughter. In the blood container we had previously poured 1 g of potassium oxalate (99.98%, Sigma-Aldrich) and 1.25 g of sodium fluoride (99.99%, Sigma-Aldrich), acting as anticoagulant and glycolytic inhibitor, respectively [4]. We then measured the glucose concentration of the blood sample by two portable glucose meters (Freestyle, TheraSense, and Glucomen, Menarini Diagnostics). We performed two measures for each meter: the average value was 65 mg/dl. Blood was then stored into a refrigerator at 4 °C. In the following hours we checked again the glucose concentration several times: the differences compared to the first measures were always within the precision of the meters, thus confirming that glycolysis was properly inhibited. Then, we properly added D-glucose to obtain blood samples with concentrations similar to those indicated above. B. Impedance measurement Within 72 hours from sample preparation we performed the impedance measures through a Solartron 1260 impedance analyzer. For the measurement cell a probe from

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Dielectric properties of water and blood samples with glucose at different concentrations

Delta OHM was chosen (SP06T model). As shown in Fig. 1, the cell is characterized by four platinum electrodes for separation between stimulation and sensing terminals, thus allowing minimization of possible secondary effects (such as inductance of cables or parasitic capacitances) that can influence the accuracy of the impedance measurement [5]. The electrodes are then surrounded by a bell: when the cell is immersed into the sample to be studied, the measurement region is delimited and kept constant. The cell also includes a temperature sensor. The cell constant is 0.7. Through the Solartron 1260 we applied a 100 mV r.m.s. voltage to the outer couple of electrodes. The electric current was read through the inner electrodes. We analyzed the impedance of the samples in the 10-1–107 Hz range. The impedance was measured in five frequency points for each decade. For each sample studied, we performed two independent measures: after the first measure the cell was cleaned before immersing it again into the sample. The impedance values presented for each sample are the average between the two measures. All the impedance measures were performed with the samples at ambient temperature (23 °C with maximum variations of ±0.3 °C). All the measures were corrected through open-short compensation technique. III. RESULTS The impedance modulus of water, and of glucose-water mixtures, is reported in Fig. 2. The modulus increased for increasing glucose concentration values in a wide frequency range. More precisely, the frequency range where the differences were more evident (we define it as reference range) was 0.1–800 Hz. Outside this range, the differences were less clear, as the modulus curves showed relatively frequent intersections at some frequency values. As regards the phase, a decrease was observed for increasing glucose values, though variations were less marked than those observed in the modulus. The reference range for the phase

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Fig. 2 Impedance modulus for glucose-water samples (pure water: empty circle; 100, 200, 300 mg/dl glucose: full circle, triangle, square, respectively) was 80 Hz–107 Hz, though from 105 Hz onwards the differences were small. Percentage difference values between the blank sample and that at the highest glucose concentration for both modulus and phase in their own reference ranges were 125±17% (mean±standard deviation) and 43±56%, respectively. Maximum and minimum values were: 135% and 63% for the modulus; 157% and 0.1% for the phase. As regards blood, when looking to the modulus and phase curves in the whole frequency range, almost no variation can be appreciated for the different samples. However, when the analysis was focused on a specific (though still wide) frequency range some differences emerged. In fact, in the 8– 2·106 Hz frequency range there was a slight but evident difference in the impedance modulus: similarly to glucosewater samples, the modulus increased for increasing glucose concentrations, as shown in Fig. 3. Outside the reported reference range, the modulus curves showed frequent intersections. Similar analysis for the phase showed that there was again a relatively wide frequency range, i.e. 2·105–8·106 Hz, where a slight phase decrease for increasing glucose concentration was observed in the whole range. Thus, in a frequency range which almost covers all the studied range at least one between impedance modulus and phase showed slight but clear variations for increasing glucose concentrations. Percentage difference values between the sample with endogenous glucose only and that at the highest glucose concentration for both modulus and phase in their own reference ranges were 2.00±0.09% and 1.51±0.11%, respectively. Maximum

Fig. 3 Impedance modulus for glucose-blood samples in a portion Fig. 1 Inner part of the measurement cell

of the studied frequency range (blood alone (65 mg/dl glucose): empty circle; 100, 200, 300 mg/dl glucose: full circle, triangle, square, respectively)

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and minimum values were: 2.24% and 1.68% for the modulus; 1.60% and 1.27% for the phase. IV. DISCUSSION In the recent years a strong effort has been carried on aimed at the development of techniques for non-invasive glucose measurement [1]. Some of these approaches have lead to the production of non-invasive glucose meters [6], but for several reasons many of them remained at prototype level. The only one available today is the GlucoWatch [7], and it has several drawbacks [6]. A promising approach for non-invasive measurement of glycaemia is impedance spectroscopy. Some device prototypes have been developed based on this approach, and one of them also reached the market [1,8,9], but it was withdrawn and the company filed for bankruptcy [10]. A new company seems to be working on a similar device [11,12], but at the moment no device is on the market. In [2] the authors claimed that the measurement of glycaemia through impedance spectroscopy is possible as variations in blood glucose concentration induce some transportation phenomena of electrolytes through the cell membrane, and that results in variations in the dielectric properties of the medium. The most relevant phenomenon is the plasma sodium concentration lowering in the presence of hyperglycaemia [13]. In [2] it was claimed that these effects are entirely responsible for the impedance variation of blood and underlying tissues, since glucose variations do not directly affect the dielectric properties of the investigated medium in the MHz band, as also stressed in other studies from the same research group [14,15]. In fact, some references were provided to other studies where the effect of variations in glucose concentration was studied in water [16,17]. In [17] it was shown that at glucose concentrations lower than 1 g/cc the dielectric properties of the glucose-water solution are not different from those of pure water. However, a more recent study contradicts these findings. In [3] the dielectric properties of glucose-water solutions were found different for glucose concentration values varying within the physiological range. In particular, the impedance modulus increased for increasing glucose concentrations within the 1 kHz – 1 MHz band. The first aim of our study was to reproduce the reported experiments on glucose-water solutions. Our results essentially confirm those of the study [3], but in even wider frequency band: in fact, in all the investigated range, i.e. 0.1 Hz – 10 MHz, we observed a significant variation in the impedance modulus, phase, or both, though the greater differences were found for frequencies lower than 100 kHz. Thus, we can claim that variations in glucose concentration even at low values such as physiological ones directly affect

the dielectric properties of a solution, independently from other mechanisms that may be induced by glucose variations. On the other hand, it is confirmed that the impedance variations due to variations in glucose are certainly more evident at low frequencies, and this may partially explain why they were not observed in the studies [16-17] where frequencies over 1 MHz were considered. It must also be noted that the partial differences between our results and those of study [3] may be due to the use of a different measurement cell. In fact, we used a four electrodes cell instead of simple two electrodes cell, thus allowing four terminal measurements less prone to noise effects at medium-high frequencies [5]. Furthermore, we used platinum instead of stainless steel electrodes, the latter being more sensitive to the effects of possible reactions with the solution at low frequencies. Few data can be found in the literature on impedance in blood at different frequencies related to glucose concentration values. In [2] some impedance data were reported from an in vivo experiment on humans where glycaemia was 100 and 200 mg/dl, though only frequencies above 1 MHz were investigated. It was shown that both impedance modulus and phase were different between the two glucose concentration values in some frequency ranges, and similarly to our results higher values were found for the 200 mg/dl concentration. As regards the modulus, which was the impedance parameter of major interest, it was claimed that the sensitivity to glucose changes was between 20 and 60 mg/dl glucose/Ω, and this was in acceptable agreement to our results, though the sensitivity that we found was slightly lower. In fact, the best sensitivity that we observed for the modulus between the 100 and 200 mg/dl samples was about 110 mg/dl glucose/Ω (100 mg/dl: 72.2 Ω; 200 mg/dl: 73.1 Ω), at frequencies around 1 kHz. In [3] the dielectric properties of blood for different glucose concentrations were studied in vivo on hamsters, and variations in the dielectric parameters were observed for glucose concentrations varying between 150 and 300 mg/dl. However, only one frequency value was investigated (10 kHz), and only semi-quantitative results were reported. Some studies investigated the dielectric properties for different glucose concentrations of PBS buffers with suspended erythrocytes [14,15]. In [14] different glucose concentrations were considered ranging from zero to about 400 mg/dl, and the analysis was performed between 10 kHz to 100 MHz. Variations in the dielectric properties of the buffers were found for the different glucose concentrations. However, the dielectric parameters showed a nonmonotonic pattern for increasing glucose values, differently to our results. In [15] the analysis was extended to 2 GHz, with similar findings. The authors claimed that this non-

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Dielectric properties of water and blood samples with glucose at different concentrations

monotonic behavior may be due to erythrocytes activities at the membrane level, but no further details were provided. In our study huge variations in the impedance parameters for different glucose values were observed only in water. This suggests that the ability of glucose to induce variations in the dielectric properties of the solution may depend on the conductivity levels involved. In fact, in blood solutions, which have conductivity much higher than water, the impedance variations were modest compared to those in water, but still clearly present. In conclusion, this study investigated the effect of glucose concentration on the impedance of different solutions, i.e. glucose in water and in blood. Few studies showed the impedance variations of blood for different glucose concentrations within the physiological range, and to our knowledge no study examined in detail the frequency values below the MHz band: this is one of the main novelties of this study. The advantage of focusing on frequency values below the MHz for possible future clinical applications may consist in a lower sensitivity to the electromagnetic noise in the environment. The study showed that glucose is able to directly affect the impedance of the investigated samples. In blood, slight but clear impedance variations for different glucose values were observed in a wide frequency range, and especially below 1 MHz. Possible indirect mechanisms involving cells may only contribute to the observed total variations.

5.

6.

7.

8.

9. 10. 11.

12.

13.

ACKNOWLEDGEMENTS The authors thank Dr. Franceschini for supply of bovine blood, and Dr. G. Sbrignadello and Dr. M.C. Scaini for their useful comments and help. The study was partially supported by a grant from Regione Veneto (DGR 2702/1009-04) and from CNR in the framework “Ricerca Spontanea a Tema Libero” (Research number: 946).

14. 15.

16.

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3. 4.

Khalil OS (2004) Non-invasive glucose measurement technologies: an update from 1999 to the dawn of the new millennium. Diabetes Technol. Ther. 6: 660-697 Caduff A, Hirt E, Feldman Y, Ali Z, Heinemann L (2003) First human experiments with a novel non-invasive, nonoptical continuous glucose monitoring system. Biosens Bioelectron. 19:209-217 Park JH, Kim CS, Choi BC et al. (2003) The correlation of the complex dielectric constant and blood glucose at low frequency. Biosens Bioelectron 19:321-324 Chan AY, Swaminathan R and Cockram CS (1989) Effectiveness of sodium fluoride as a preservative of glucose in blood. Clin Chem 35:315-317

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Awan SA, Kibble BP (2005) Towards accurate measurement of the frequency dependence of capacitance and resistance standards up to 10 MHz. IEEE Trans Instrum Meas 54:516520 Tura A, Maran A and Pacini G (2006) Non-invasive glucose monitoring: Assessment of technologies and devices according to quantitative criteria. Diabetes Res Clin Pract. In Press (DOI: 10.1016/j.diabres.2006.10.027) Tierney MJ, Tamada JA, Potts RO et al. (2001) Clinical evaluation of the GlucoWatch (R) biographer: a continual, non-invasive glucose monitor for patients with diabetes. Biosens Bioelectron 16:621-629 Pfutzner A, Caduff A, Larbig M et al. (2004) Impact of posture and fixation technique on impedance spectroscopy used for continuous and noninvasive glucose monitoring. Diabetes Technol Ther 6:435-441 Weinzimer SA (2004) PENDRA: the once and future noninvasive continuous glucose monitoring device? Diabetes Technol Ther 6:442-444 Wentholt IM, Hoekstra JB, Zwart A et al. (2005) Pendra goes Dutch: lessons for the CE mark in Europe. Diabetologia 48:1055-1058 Forst T, Caduff A, Talary M et al. (2006) Impact of environmental temperature on skin thickness and microvascular blood flow in subjects with and without diabetes. Diabetes Technol Ther 8:94-101 Caduff A, Dewarrat F, Talary M et al. (2006) Non-invasive glucose monitoring in patients with diabetes: a novel system based on impedance spectroscopy, Biosens Bioelectron 22:598-604 Hillier TA, Abbott RD and Barrett EJ (1999) Hyponatremia: evaluating the correction. factor for hyperglycemia. Am J Med 106: 399-403 Hayashi Y, Livshits L, Caduff A (2003) Dielectric spectroscopy study of specific glucose influence on human erythrocyte membranes. J Phys D: Appl Phys 36:369-374 Caduff A, Livshits L, Hayashi Y (2004) Specific D-glucose Influence on Electric Properties of Cell Membrane at Human Erythrocyte Studied by Dielectric Spectroscopy. J Phys Chem B 108:13827-13830 Fuchs K, Kaatze U (2001) Molecular dynamics of carbohydrate aqueous solutions. Dielectric relaxation as a function of glucose and fructose concentration. J Phys Chem B 105:2036-2042 Mashimo S, Miura N, Umehara T (1992) The structure of water determined by microwave dielectric study on water mixtures with glucose, polysaccharides, and L-ascorbic acid. J Chem Phys 97:6759-6765 Corresponding author: Author: Institute: Street: City: Country: Email:

Andrea Tura, PhD ISIB-CNR Corso Stati Uniti, 4 Padova Italy [email protected]

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FENOTIP: Microfluidics and Nanoelectrodes for the Electromagnetic Spectroscopy of Biological Cells V. Senez1, A. Treizebré1, E. Lennon3, D. Legrand2, H. Ghandour1, B. Bocquet1, T. Fujii3 and J. Mazurier2 1

IEMN/CNRS-USTL-ISEN, University of Lille, 59652 Villeneuve d’Ascq, France 2 UGSF/CNRS-USTL, University of Lille, 59652 Villeneuve d’Ascq, France 3 CIRMM/IIS, University of Tokyo, 153-8505 Tokyo, Japan

Abstract— This work is focused in the area of ligandreceptor interaction analysis. The purpose is to be able to assign, in real time, a specific crossing pathway to a ligand/receptor pair, without the use of molecular labels. The classification is based on changes in the electrical properties of the cells. Various BioMEMS have been designed and fabricated in order to characterize the variation of the electrical properties of the biological cells. We are interested in both dielectric (i.e. polarization) and vibrationnal (i.e. absorption) spectroscopy. Several devices are currently tested for low (40GHz) frequency range (LFR & HFR) measurements. In the LFR, we have fabricated coplanar and 3D electrodes sensors for impedance measurements. In the HFR, we have designed and processed coplanar waveguides. In the LFR, we have performed static and dynamic measurements on small cluster of cells. In the HFR, we have shown that we can propagate microwaves along submicrometer single wires (Goubau propagation). We are going to use these HFR devices for measurement on small cluster of cells. Keywords— Living Cell, Cell Signaling, Dielectric & Vibrationnal Spectroscopy, Biomems, Nano-Electrode and wire.

I. INTRODUCTION Biological cell analysis is a very important field of research. Currently, the prevailing paradigm to analyze cellular functions is the study of biochemical interactions using fluorescence based imaging systems. However, the elimination of the labeling process is highly desirable to improve the accuracy of the analysis. Recent developments in microand nanofabrication technologies are offering great opportunities for the analysis of biological cells; the combination of micro fluidic environments, nano-electrodes/wires and ultra wide band electromagnetic engineering will soon make possible the investigation of local (submicrometer scale) dynamic processes integrating several events at different time scales. In the paper, we present our work which aims at investigating living-cells with the help of MEMS and NEMS (Micro and Nano Electro Mechanical Systems) and ultra wide band (DC-THz) electromagnetic characterization techniques. We are working with a well-characterized biological model

(ligand: lactoferrin, receptors: nucleolin and sulfated proteoglycans) [1]. We propose to follow the various phases of assembly between the ligands and receptors present or not on a set of mutant CHO cell lines and internalization of the ligands/receptors complexes into the cells (Fig. 1). II. MICRODEVICES AND TECHNOLOGIES Permittivity measurements across a range of frequencies provide information about the species and their chemical environment. Features in dielectric spectrum (the polarization relaxation) are classified as α-, β- and γ-dispersion. In the HFR range, the spectrum may exhibit rotationabsorption phenomena. For biological species, access to a broad frequency range is absolutely necessary due to their size and chemical diversity. That is why we are currently investigating different types of structures. We have tested various methods for the immobilization of the cells: i) mechanical (Fig. 2a), ii) chemical (Fig. 2b) and 3) electrical (Fig. 2c).

Fig. 1 Binding of lactoferrin on two mutants CHO cells. CHO 677 line does not allow endocytosis of lactoferrin.

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 170–173, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

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Fig. 3 Impedance microsensor (4-points): a) 3D silicon and planar gold electrodes, b) 3D and planar gold electrodes. Channels are made of PDMS.

Fig. 2 a) Single cell measurement set-up using deformability of cell between 3D electrodes; b) Patterning and immobilization of CHO cells on glass substrate by surface treatment with OTS and amine; c) Microfluidic chip for dielectrophoretic immobilization of single cells. In the low frequency range (LFR) ( ∑t(S)), duration of each stage of hard bolus processing is longer than those for the soft bolus (t1(H) > t1(S), t2(H) > t2(S), t3(H) > t3(S)), frequency of closing movements of the hard bolus processing is greater than for the soft bolus (f(H) > f(S)), duration of the bolus processing for men is longer than for women - influence of gender and duration of the bolus processing is longer for older people - influence of age. III. RESULTS

The chewing movements of 55 subjects with natural dentition were recorded. Due to problems related to the sensor attaching to the front teeth, records of four subjects could not be used for the analysis. Therefore, statistic analyses were performed on the remaining 51 subjects.

Table 1 Table of measured durations and frequencies H - hard food, S - soft food; t1 [s], t2 [s] and t3[s] - phase durations (chopping, grinding, swallowing); ∑t - summation of t1, t2 and t3; ∑f - total frequency; Average - arithmetical average of measured quantity; Max, Min - maximal and minimal value of measured quantity; SD - standard deviation of measured quantity.

Average Minimum Maximum SD

t1[s] 6.5 1.2 17.7 4.0

t2[s] 13.9 3.1 62.0 9.7

H t3[s] 7.6 0.8 34.5 6.1

Fig. 2 An example of the lower jaw motion during H and S bite processing in the local coordinated system

Σt [s] 28.0 7.8 78 15.0

Σf [Hz] 1.5 0.8 2.9 0.5

t1[s] 4.7 0.2 11.5 3.1

t2[s] 11.3 2.5 40.1 7.9

S t3[s] 5.9 1.6 21.3 3.7

Σt [s] 21.9 6.6 52.3 11.1

Σf [Hz] 1.5 0.9 2.9 0.6

Fig. 3 Typical trajectory of chewing movements of one patient (in y axis) divided into three stages to illustrate the individuality of the bolus processing

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soft one Σt(H) > Σt(S) (p= 0.001). Also, the duration of the each stage of hard bolus processing was longer than those for the soft bolus. This difference was statistically significant for t1(H) > t1(S) (p=0.005) and t2(H) > t2(S) (p=0.025), but not for t3(H) > t3(S) (p=0.064). The third hypothesis regarding the influence of the bolus character on the frequency of closing movements during the mastication (f(H) > f(S)) was not supported, because the same average number was achieved for both types of boluses. Only during swallowing phase the frequency of closing movements was significantly higher (p=0.003) for the hard bolus than for the soft one. The gender and age influenced nor time nor frequency of bolus processing, so hypotheses IV. and V. are not confirmed.

Fig. 4 Typical trajectory of chewing movements of two different patients (in y axis) divided into three stages to illustrate the individuality of the bolus processing

The path of the sensor rigidly connected to the lower jaw was graphically expressed in all axes (x, y, z) for each subject and for each measured motion (hard bite - H, soft bite - S) (Fig. 2). Curves of the mandibular movement trajectory showed that masticatory movements are markedly individual (Fig. 2, 3 and 4). Many of the curves could be easily segmented into phases of bolus chopping, grinding and swallowing (Fig. 2, 3 and 4). Conversely, some subjects chewed in the same manner most of the time (Fig. 3). Also the bolus character influenced the trajectory of lower jaw movements (Fig. 4). All measured quantities were averaged; maximal, minimal and standard deviation (SD) values were calculated (Table 1). Data were also examined from subject’s gender and age point of view. To analyze the dependence of measured quantities on the age, participants were grouped according decades (Table 2). The statistical significance was performed by paired and unpaired Student t-test and Fischer’s exact test. The age criterion was evaluated by analysis of variance. The data shown above support the first two hypotheses that the bolus character influences the process duration. The hard bolus was chewed significantly longer than the Table 2 Table of gender and age distribution Age group 20-30 31-40 41-50 51-70

Men 12 3 2 1

Women 16 7 4 3

Total 28 10 6 4

IV. DISCUSSION AND CONCLUSION Results obtained in this motion analysis confirm data from a similar study [1] concerning the influence of individual chewing habits. Overall motion of the point in the defined coordinated system can be used to reconstruct the 3D motion. The design of the experiment using one marker as a mandible position-reading instrument sufficiently served as detection of translational degrees of freedom. Three markers were used [1] in order to detect the rotational and the translational degrees of freedom, but rotational movements were not useful for the evaluation of the jaw movement parameters. The hypotheses that the bolus character affects the processing duration were confirmed. The results show the high individuality of timing of the chewing maneuver, especially during the chopping and grinding phases. The level of significance when comparing chewing duration display, that in the first phase - chopping (p=0.005) are bigger differences than during grinding (p=0.025). The timing of the swallowing (t3) was not significantly different (p=0.064). The same frequency during mastication indicates that the bolus character does not influence masticatory movements. A significant difference between frequencies was found during swallowing only and could reflect a different texture between pastry and nuts (fine particles) at the time of swallowing. Alternatively, this finding could have been influenced by salivation. These findings agree with the theory that mastication is a highly individual process influenced not only by anatomy, but also by a specific manner developed during life. Similar findings were performed by Gerstner [1]. The observed decrease of the amplitude in craniocaudal (opening, closing) movements support the hypothesis that the stage of the bolus processing influences the shape of the curve illustrating movement of the mandible and thus the

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Biomechanical Analysis of Bolus Processing

direction of the actual chewing force. Computed trajectories agree with observations by Bhatka [4] that the center of lower jaw motion moves along an elliptically shaped curve. Understanding masticatory development and physiological relationships are important in determining the principal anatomical direction during closing movements and the resultant direction of the loading during mastication. Such findings can be used to plan treatment and to reconstruct defective dentition from a masticatory point of view, as well as to validate treatment procedures. Results can also affect the design and the usage of materials for the dental implants, their position in jaws and the shape of the occlusal surface of bridgeworks and dentures. The obtained information suggests that masticatory movements vary by individual. Therefore the relationship between mandible movements and direction and the magnitude of the chewing force should be more precisely examined.

ACKNOWLEDGMENT The research has been supported by the Ministry of Education project No. MSM 6840770012 and by the Grant Agency of the Czech Republic under project No. 106/06/0849.

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6. 7.

Gerstner G E, Lafia C, Lin D (2005) Predicting masticatory jaw movements from chin movements using multivariate linear methods. Journal of Biomechanics, 38:1991–1999 Klepáček I, Mazánek J (2001) Klinická anatomie ve stomatologii. Grada Publishing, Avicenum, Praha Voldřich M. (1969) Stomatologická protetika. Státní zdravotnické nakladatelství, Praha Bhatka R, Throckmorton G S et al. (2004) Bolus size and unilateral chewing cycle kinematics. Archives of Oral Biology, 49:559–566 Eskitascioglu G, Usumez A. et al.. (2004) The influence of occlusal loading location on stresses transferred to implant-supported prostheses and supporting bone: a three-dimensional finite element study. The Journal of Prosthetic Dentistry, 91:253–257 Zatsiorski V M (1998) Kinematics of Human Motion. Human Kinetics. Champaign, IL Abdel-Aziz Y I, Karara H M (1971) Direct linear transformation from comparator co-ordinates into object space co-ordinates, Proc. ASP/UI symposium on close-range photogrammetry, Am. Soc. of Photogrammetry, Falls Church, VA, pp. 1-18

Author: Tomas Goldmann Institute: CTU in Prague, Faculty of Mechanical Engineering, Dept. of Mechanics, Biomechanics and Mechatronics Street: Technicka 4 City: Prague 6 Country: Czech Republic Email: [email protected]

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Changes in Biomechanics Induced by Fatigue in Single-leg Jump and Landing J. Stublar, P. Usenik, R. Kamnik, M. Munih Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Sloveni Abstract— The purpose of this study was to determine the effects on lower extremities during muscle fatigue. The experimental trial of single-leg landing and jumping was conducted in a group of healthy male subjects. The experimental protocol included series of single-leg landings from elevated platform, single-leg jumps and fatiguing process that was kept at reasonable level, by asking each subject to make total of 60 two-legged squats. The results show that there was no significant change in overall shock attenuation prior and after the experiment. However the ankle work decreased, while the hip work increased. Even though the fatigue caused significant decrease in peak moments at the hip, knee and ankle joints, the significant increase in hip range of motion resulted in constant overall shock attenuation. The results suggest that the lower extremity is able to adapt to fatigue due to redistributing work to larger hip muscles. Keywords— single-leg jump, fatigue, kinetics, kinematics, muscle

I. INTRODUCTION In dynamic maneuvers, when impacting with the environment, the mechanical shock experienced by the body, must be attenuated by the musculoskeletal system. It was shown that in sports such as basketball, netball, volleyball, football, gymnastics and aerobic dance the injuries due to landing are prevalent. It was demonstrated that the shock in landing is mainly attenuated by the eccentric muscle activity. On this basis it was hypothized that the muscle fatigue would significantly decrease the shock attenuation ability of lower extremities [1]. Various studies investigated the biomechanics of landing. In [2] it was shown that the hip and knee flexion increased and ankle flexion decreased at touchdown with fatigue during single-leg landing. Consequently, the hip joint work increased, while the ankle joint work decreased. A similar study showed that in fatiguing single-leg landing the ankle and knee flexion increased, while in hip no significant flexion changes were observed [3]. In this experiment, the joint work changed in a similar way as in [2] at early fatigue progression, while this trend reversed during further fatiguing and the joint work values returned to original values. The objectives of our study were to verify the changes of biomechanics in single-leg landing and jumping activity with induced fatigue. In the next chapter the methodology

of experimental testing of a group of students is presented. In the following section the results are outlined and discussed in the final section. II. METHODS A. Subjects Six healthy male subjects with no severe previous lower extremity injury participated in this study. The age, height and weight of the subjects, who were all left foot dominant, were 22.8 years (SD 1.0), 185.0 cm (SD 6.4) and 92.9 kg (SD 16.8), respectively. B. Data collection Ground reaction force (GRF) and kinematics data were collected during the initial preparation session. GRF data were sampled at 100 Hz from AMTI force plate (AMTI, Inc., Newton, MA, U.S.A.). The kinematics of the body segment movement were obtained by the OPTOTRAK optical system (Northern Digital Inc., Waterloo, Canada) measuring the 3-D positions of active infrared LED markers at a 100 Hz sample rate. Seven markers were placed on the left side of the body according to Table 1. Table 1 Positioning of LED markers on the human subject Marker number 1 2 3 4 5 6 7

Position Left foot (little finger) Left foot (heal) Left ankle Left knee Left hip Mid trunk – left side Left shoulder

C. Experimental protocol During the practice session subjects were asked to perform four series of single-leg landings and jumps. During each series subject went through fatiguing process. Squatting was used to induce fatigue because it is considered as a closed kinetic chain movement that typically involves mul-

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 288–291, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Changes in Biomechanics Induced by Fatigue in Single-leg Jump and Landing

Fig. 1 Start position of experimental trial and landing tiple muscle groups including the hip extensors, knee extensors, and ankle plantar flexors. After minor individual warm-up, subjects were asked to stand on a 30 cm high elevated platform (see Fig. 1, left) using only their left leg to support themselves and than land as vertically as possible on the force plate (see Fig. 1, right). Participants were instructed to use a toe-heel landing strategy. After performing two single-leg landings, subjects stepped on the force plate and performed two additional single-leg jumps. Subject repeated this sequence of landings and jumps after fatiguing process of several squats (10 after first series, 20 after second and 30 after third). At the end, the subject’s fatiguing process consisted of total 60 squats. Upper extremity movement was constrained throughout experiment by asking subjects to keep their hands on their back. D. Data analysis The signals collected from active markers and force plate were interpolated and filtered using a fourth order zerophase Butterworth filter with a 5 Hz cutoff frequency [4]. The coordinate systems of all the sensors were transformed to coincide with the reference coordinate system placed on the centre point of force plate. To estimate net muscle moments during the procedure, the body was modeled as a 3-D system of four rigid body segments embodying the foot, shank, thigh and trunk (including upper extremities and head). Collected data were used to compute segmental anthropometric parameters (segment masses, mass centers and inertia tensors), based on the De Leva study [5]. From the segment position, orientation and other anthropometric data, the forces and torques acting on the joints were calculated

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recursively using Newton-Euler inverse dynamic analysis [6]. This analysis is based on the Newton’s law that states that the sum of the external forces acting on a rigid body, and similarly, the sum of the external moments acting on a rigid body is equivalent to the time change in the linear and angular momentum of the body, respectively. Thus, the human body can be modeled as a chain of constant mass and rigid body segments whereby for each segment, the external forces and moments consist of a net force and a net moment reaction at both the proximal and distal joints and a gravitational force. Additional forces are involved in the segments where interaction with the environment occurs. Ground reaction force vectors acting from the floor on the foot were measured and thus readily used in the analysis. Each joint power at time t was given by: Pi(t) = Mi(t) × ωi

(1)

where Mi is the resultant joint moment and ωi is the joint angular velocity. Work done by each joint throughout the motion was calculated by integrating the power with respect to time during trial: Wi =

∫ P (t) dt i

(2)

In equations above, the subscript i denotes the index of particular joint. One-way ANOVA was used to test for significant differences between unfatigued and fatigued series. Significance level was set at P-Value < 0.05. Peak GRF, range of motion, peak moment, peak power and net work at each joint were compared. All measured data were processed using the Matlab 7.0 software (MathWorks, Inc., Natick, MA, U.S.A.). III. RESULTS Because of insignificant difference between the first three series, the second and the third series were excluded from further analysis. Therefore, the first series represents rested muscles and the last series the muscles after fatiguing process of 60 squats. Take-off and landing phases of the jump were studied separately. From this reason, all figures were divided into three sections separated by two dashed lines. The left section corresponds to the take-off stage (see Table 2), the middle to the mid-air stage and the right to the landing stage (see Table 3). The GRF was normalized to the subjects body weight (mass times ground acceleration), the moments and net work in all joints were normalized to the subjects mass in order to compare values between all subjects. All presented

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Table

2 Group mean (SD) data for the first and the last cycle for the take-off kinematics and kinetic variables. First cycle

Last cycle

P-Value

Peak GRF 1.94 (0.18) 1.88 (0.21) 0.258 Range of motion [°] Hip 52 (6) 51 (6) 0.967 Knee 55 (5) 56 (7) 0.593 Ankle 59 (10) 54 (9) 0.129 Peak moment [Nm/kg] Hip 6.31 (1.42) 6.06 (1.05) 0.114 Knee 4.02 (0.55) 3.99 (0.55) 0.531 Ankle 3.74 (0.56) 3.44 (0.91) 0.007* Peak power [W/kg] Hip 27.72 (4.46) 25.63 (3.86) 0.044 Knee 19.85 (2.33) 19.8 (3.92) 0.810 Ankle 18.63 (5.7) 16.32 (5.56) 0.090 Net Work [J/kg] Hip 4.73 (0.83) 4.42 (0.81) 0.270 Knee 3.2 (0.48) 3.18 (0.5) 0.090 Ankle 2.74 (0.76) 2.36 (0.7) 0.060 Overall 10.6 (1.46) 9.89 (1.35) 0.090 * Indicates significant difference between first and last cycle (P < 0.05).

Table

3 Group mean (SD) data for the first and the last cycle for the landing kinematics and kinetic variables. First cycle

Last cycle

For studying the landing phase, the measurements collected from the single-leg landing from the elevated platform were used. The landings from the elevated platform proved to give more significant results in contrast to singleleg jump. Both landing kinematics and kinetics are significantly different during the last series. The most significant was the decrease in peak GRF and peak moment in hip and ankle joints. Also significant were the increase in hip and decrease in ankle range of motion, thus proving the hypothesis on shift of shock attenuation from ankle to hip joint. In Fig. 3 the increased motion in all joints during last series can be observed. This observation is rather surprising considering that, in order to flex joint, muscles must provide additional work. The effects of fatigue are clearly shown in Fig. 4 where all joint moments are significantly smaller during the landing phase. Important and significant is the observation of the net knee work shown in Fig. 5, what 2.5 GRF [times body weight]

results in Table 2, Table 3, Fig. 2, Fig. 3, Fig. 4 and Fig. 5 were averaged over all participating subjects. In the brackets the standard deviation (SD) throughout the group is stated. The difference in mean value throughout all data is smaller than the SD value, thus in order to distinguish the significant difference the P-Value parameter was used. During the take-off stage the only significant change was the decrease of peak ankle moment during the last series. Peak moments in hip and knee joints were also decreased during the last cycle, which could correspond to diminished muscles ability due the fatiguing process.

51 (17) 51 (8) 44 (8)

0.019* 0.049* 0.023*

5.99 (0.6) 3.55 (0.66) 3.35 (0.77)

Eirrev is irreversibly permeabilized (see the color bar in Fig. 3). In the first two models of cutaneous protruding and subcutaneous non-protruding tumor (Fig. 2a and Fig. 2b) the specific conductivity of the target tissue is equal to the specific conductivity of the surrounding tissue. Since, these two models are assumed to be homogeneous, the electric field distribution does not depend on the specific conductivities of the tissues, but only on the electrode size and position, as well as the amplitude of the applied voltage. By the comparison of the local electric field distribution within these two models one can appreciate the influence of the target tissue geometry on the successful electropermeabilization (E > Erev). Namely, for successful electropermeabilization of cutaneous protruding tumors lower amplitude of voltage need to be applied on the electrodes compared to the needed voltage for successful electropermeabilization of subcutaneous non-protruding tumor, while the shape and distance between electrodes are kept constant. The model of subcutaneous tumor gives the user an insight into the electric field distribution within the target tissue when electroporated through the skin. This model is composed of two layers; the upper layer representing skin tissue with lower specific conductivity compared to the underlying layer being more conductive. Unlike the previous two homogeneous models the electric field distribution in this model depends on geometrical and electrical properties of both tissues. The electric field distribution is presented by two models with two different thicknesses of the skin layer: 1 mm (see Fig. 2c) and 3 mm (see Fig. 2d). The aim of this part of educational content is to contribute to the understanding of the influence of the specific conductivity and the thickness of the skin layer on the electric field distribution within the underlying tissues where the target tissue (subcutaneous tumor) is located. Thus, the user can appreciate the influence of the skin thickness on electric

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field distribution in the target tissue and surrounding tissues. The key message is that in order to successfully electropermeabilize the target tissue being electroporated through the thicker skin layer (3 mm) a higher voltage need to be applied compared to the needed voltage for successful electropermeabilization of the same target tissue being electroporated through the thinner skin layer (1 mm), while the shape and distance between electrodes are kept constant. Based on this the user is offered both the basic explanations on the role of the highly resistive skin tissue (specially stratum corneum) in electric field distribution within treated tissues and the guidelines about how to overcome the highly resistive skin tissue in order to permeabilize more conductive underlying tissues. In Fig.3 the electric field distribution inside the cutaneous protruding tumor obtained with two different amplitudes of applied voltage (Fig. 3a: U=300 V and Fig. 3b: 600 V) using two parallel plate electrodes is shown as example. The comparison of these two figures demonstrates that by increasing the applied voltage on the electrodes (for the same tissue geometry, electrode size and position) the eleca)

tric field becomes more intense and extends toward the central volume of the tumor. Similar effect can be achieved increasing the extending the electrode length (in our case by switching from 4 mm to 7 mm electrode length the entire volume of encircled region can be subjected to the E > Erev). The educational web pages are concluded by a test that gives the user an opportunity to test the acquired knowledge, while allowing the teacher and the web-developer to follow the efficacy of the constructed pages and their educational contents. The important property of the educational web-application is that it is upgradeable so that the present contents can be modified and new contents easily incorporated. IV. CONCLUSIONS The educational content of our web-based application will contribute to the understanding of mechanisms underlying the electropermeabilization process in biological tissues. It is especially aimed at providing the knowledge about the parameters of local electric field being important for successful electrochemotherapy. The objective of the e-learning application is also to give the suggestion/guidance to all practitioners as to choose the needed shape and placement of electrodes, as well as the appropriate amplitude of electric pulses in order to increase the electrochemotherapy outcome.

REFERENCES 1.

2.

b)

3. 4. 5.

Marty M, Sersa G, et all (2006) Electrochemotherapy – An easy, highly effective and safe treatement of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Prosedures of Electrochemotherapy) study. EJC Supplements 4: 3-13 Day A J and Foley D J (2006) Evaluaing a web lecture intervention in a human-computer interaction course. IEEE Trans Educ 49: 420-431 Humar I, Sinigoj A, Bester J, and Hegler O M (2005) Integrated component web-based interactive learning systems for engeneering. IEEE Trans Educ 8: 664-675 Dale E (1969), Audio-Visual methods in teaching. 3rd ed. New York: Holt, Rinehart, and Winston www.ltfe.org Author: Selma Corovic Institute: Street: City: Country: Email:

Faculty of electrical Engineering, University of Ljubljana Trzaska 25 Ljubljana Slovenia [email protected]

Fig. 3 Electric field distribution inside the protruding tumor for two different the applied voltages (U) on the electrodes: a) U=300 V and b) U=600 V

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Assessment of a system developed for virtual teaching M.L.A.Botelho1, D.F.Cunha2 , F.B.Mendonca3 and S.J.Calil4 1

Universidade Federal do Triangulo Mineiro (UFTM), Biologics Sciences Department (DCB), Uberaba-MG, Brazil 2 Medical Clinical Department, UFTM, Brazil 3 Lidercomp Informatica Ltda, Uberaba-MG, Brazil 4 Biomedical Engineering Department (DEB), Universidade Estadual de Campinas (UNICAMP), Brazil

Abstract - There is today a worldwide search for ways to present electronic courses through Internet. There are also a significant number of products to attend such search. Most of these programs however are designed for management rather then to help the teacher on the creation and implementation of a lecture. Among the programs offering such facilities within the Brazilian market, few can be afforded by people within the academic area. It is presented here the results of a survey to evaluate a Brazilian system that was developed to create and implement a distant education course. Keywords - Distance education, E-learning, Biomedical informatics, Internet. I. INTRODUCTION

In the near future there is a strong probability for the convergence of two paradigms within the educational system of last century: the conventional teaching, and the open education at distance [1, 2]. Nowadays, the computer already takes part of the educational resources, as a complementary for improvement and possible change on the quality of the teaching and learning processes [3]. To understand the several types of electronic applications for educational purposes available in the world market, a detailed survey was carried out. The considered systems were installed in a microcomputer Pentium IV, and its functionalities were tested. Demos, tutorials, folders and manuals were also used. The compilation of the most relevant data of this work was already published [4], and one of its conclusions was that there are few options in the Brazilian market suitable to the limited resources to the majority of the university teachers. This text, part of a doctorate thesis [4], reports the results of the evaluation process of a system developed for the preparation and presentation of virtual classes using Internet. The basic premise of such project was that it should be used by people who were not specialists in computer science and that it should not demand sophisticated resources of hardware and software.

II. METHODS

A. Description of the system to be valued characteristics: Aiming at an environment as friendly as possible, with intuitive navigation and easy operation, the developed system established basic functionality requirements, like: • • •

Standard interface in all screens of the system, with Help function available during all the interactions with the system; System installations and operations as the most simple as possible; The educational material already produced by the teachers in their work, must be used in presentations preparations in the system, without difficulties.

All programs were developed to run in Windows platform, using Delphi 6 and Microsoft Direct X. The system allows class presentations online or offline (previously recorded lecturers). In both the available presentations, the interface screen has identical configuration, as presented by Figure 1, which shows the screen of an online class. There are four small windows: the teacher image (above left), the slide show (bigger part in the center), the slide title (down left), and the chat area (the window below the slide). Two work platforms are offered, for each user's type: the Teacher platform, which has the actions to create and/or to

Figure 1 –Screen format used for the virtual class.

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alter projects, to perform the presentation and to choose the configuration of the presentation. The other one is the Student platform, which has identical appearance of the teacher’s one, but does not offer the options to create or alter projects. To create an offline project, the teacher should first prepare the slide show, the audio and video of his presentation, and a text file with the topics that will be presented. After uploading these three files, it is possible for the developer to associate any frame of the just created video with any slide from the slide show. So, during the audio and video presentation, the slides are sequentially changed according to the subject being presented. To create an online project, the system imports the slide show and the topics to be presented, likewise described previously. However, the image and the voice of the teacher will be captured and transmitted by his equipment during the presentation as video streaming. The communication protocol used is TCP-IP. The system installation in a computer can be done using a CD, or through a link at an Internet site. The contents of an offline class can be accessed using the same procedures, and opened in the system with easily identifying functions. To attend an online class, the student should inform his/her identification and the IP number of the teacher’s computer, during the class timetable. The system carries out the connection and fetches the FTP server address to download the slide show to the student’s computer. During the presentation, the connection is used solely for the audio and video streaming, and for the chat. B. The system evaluation: The system evaluation followed a Test Plan, where each Test was the presentation of a class. There were two main phases: the Beta Tests, when the development of the system was still not completed (the called Beta Phase), and the Final Tests, when the programming had being ended. Here it is described the Final Tests, when the test participants filled out a spreadsheet to grade the parameters of the Evaluation Criteria that was based on Software Engineering Theory [5]. These parameters are: Efficiency, Stability, Portability, Usability, Satisfaction Degree, and the Acceptance Test [6]. After each test, teachers and students were invited to fill up a questionnaire. The answers were then statistically analyzed to learn about the user satisfaction to participate in distant lecturers and if he/she would like to continue to use the developed method

M.L.A.Botelho, D.F.Cunha, F.B.Mendonca and S.J.Calil

To carry out the tests about the offline class presentation, two teachers prepared lecturers on subjects concerning Embryology and Physiology. One hundred and eighty seven CD's, containing the lectures and the questionnaire, were distributed for students attending courses on Medicine, Nursing and Biomedical Science. One hundred answers were obtained. For the tests of the online classes, two teachers carried out presentations for thirty-eight students, on medical subjects (Medical course) and on informatics subjects (for courses on Computation and Information Systems). It was asked to students to fill a questionnaire that they would receive by e-mail. Twenty-nine answers were obtained. III. RESULTS

A. The System Performance Evaluation Results: In the tests carried out using the offline classes, all the Evaluation Criteria presented the best grades, reaching the top scores. In the tests for the online classes, however, the Evaluation Criteria concerning the general performance of the system (Efficiency, Stability, Satisfaction Degree) presented an average score of 1,25 (scale from 0 to 2). The other Criteria reached grade 2. B. The Students Answers Results: The analysis of 129 received questionnaires (online and offline classes) showed that the students valued in a positive manner the participation on virtual classes using this environment. Figure 2 shows a graphic that illustrates the distribution of these answers to the question about their appreciation for the virtual class. It can be seen that only 2,33% disliked the virtual class system Figure 3 shows a graphic that illustrates the distribution of the student’s answers to the question about if they would like to attend more classes using this system in their course. Only 4,7% were sure about their dislike for this kind of system.

Figure 2 – Distribution of the student’s answers to the question about their appreciation for virtual classes using this system.

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Figure 3 – Distribution of the student’s answers to the question about their likeliness to attend more classes using this system in their course. Figure 4 shows the results of the student’s answers to the question about the use of this system in their courses. Here, the answers were divided by the type of class they have attended. For the students who attended the offline classes, only 1% was sure they would not like to have such system in their course. On the other hand, this kind of certainty was a lot higher for the online class students (17%). Figure 5 shows the results of the evaluation for technical quality of the system performance, associated to the types of classes (offline and online). Two groups of grades are shown: the answers that resulted as Excellent (E) were added up to the ones resulted as Good (G), and the answers that were graded as Bad (B) were added up to the Worst (W) ones. 95% of those who attended to offline class marked E or G. In the online presentation group, 77% did the same, and 23% marked B or W. Only the groups that assisted the online classes used the chat, and 100 % of the students rated as Excellent or Good. A total of one hundred and seven students (82,95 %) choose the option “Possibility to watch lecture more then once”, and forty-seven (36,43 %) choose the option “Possibility to attend the class in my environment, without having to go out from home”. It is important to say that there was more than one option for this question.

Figure 5 – Comparison of the technical evaluation, by type of class. Around 66% of the students did not answer the question on “what they dislike most about the system”; 17,6% found the environment “cold”; 10,4 % marked the option “I missed the colleagues” and 6% made mark the option “I did not like having class using a computer”. C. Results of Teacher’s Answers: The results from the teacher’s answers to the Evaluation Questionnaire were: •

100 % answered they liked the environment of virtual class;

•

25% answered that the installation is easy and 75% that found a bit difficult;

•

100% answered that the class preparation presented moderate difficulty, and that the offered tools were easy to use;

•

75% answered that the teaching moment is easy, and 25% said that it presented mild difficulty;

•

50% answered rated as excellent the available tools for the presentation class, and 50 % rated as good;

•

75% answered that the students liked the new technology and 25% said that only part of them were interested;

•

for the question about “what they liked more”, they all mention the fact of being able to re-use the class already developed other times;

•

to the Test of Acceptance, 75% answered “Yes”, and 25% “Perhaps”. IV. DISCUSSION

Figure 4 – Student’s answers to the question “Would you like to keep on using the system in your course”, presented separated by type of class they had attended.

From the development phase to its test, the system designed to prepare and present offline classes did not

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present difficulties during its analysis or during its development. Even in the Beta and Final Tests presented any problem. It received the best grading to all the questions during the student’s and the teacher’s evaluations. Conversely, the application of online classes presented difficulties to all the development phases. The biggest difficulty of programming phase was the synchronization between the slides, the image and the voice of the teacher during the class presentation. This problem was solved after the development of a technique, already described [4], that made possible the perfect synchronization. During the tests, the principal problem detected with the online classes could be summarized in the observation of a teacher: "the system has his performance directly connected to the efficiency of the video transmission”. So, among the system functionalities, the audio and video streaming is the critical point. When the involved computers (both the clients and the server) have not the Internet connection at constant and excellent quality, the whole performance of the system is reduced. Furthermore, the concurrent data traffic is also a factor which compromises the system’s speed. If just one of the class participants, during the lecture, executes a download of a big file (like a movie, for example), the performance of the whole system is also reduced. The difficulty in carrying out the online classes can be observed by the grades given for the questions related to the technical quality for both types of classes presented by Figure 5. The offline classes evaluations is much better.

This work allows the observation that efforts could and should be carried out to include the Brazilian graduation system within the digital world; good results certainly are expected. The sample of students and teachers collaborators are interested in employing virtual classes in day by day work, which demonstrates that the Brazilian universities can use this resource for enrichment of the teaching and learning processes.

ACKNOWLEDGMENT The first author was a doctorate student in the PICDT/CAPES/MEC.

REFERENCES 1. 2.

3. 4.

V. CONCLUSIONS

5.

With these finds reported, it is observed that the speed and the quality of the Internet transmission, as it is today, represent a serious limitation factor to the use of the open Education, in Brazil. Certainly, differentiated services, like the Internet 2, will offer better ways to universities implementing online events. On the other hand, the offline presentations available at Internet showed few difficulties of implementation, and great acceptance from the teaching community, as demonstrated. Some specialists devoted to the open educational system suggest that those institutions that failed to embrace technological progress will be unable to provide the future demands [7, 8]. However, it is not the simple conversion of the course contents or their curricula that must take place, but how the educators see the education itself. The development of skills is necessary to maximize the benefits and the potential that the information technologies and communication offer to the education arena [9].

6.

7.

8. 9.

Moore, M.G., Kearsley, G. (1996) Distance Education: A Systems View, Wadsworth Publishing Company. Belmont (USA). Moran, J.M. (2004) Propostas de Mudancas nos Cursos Presenciais com a Educacao On-line. 11o Congresso Internacional de Educacao a Distancia. 8/09/2004. Salvador, BA. Valente, J.A. (1995) “Diferentes Usos do Computador na Educacao” In: Computadores e Conhecimento: Repensando a Educacao. Nied/Unicamp. Botelho, M.L.A. (2007) Concepcao, Desenvolvimento e Avaliacao de um Sistema de Ensino Virtual. Tese de doutorado. Departamento de Engenharia Biomedica. Faculdade de Engenharia Eletrica e de Computacao, Universidade de Campinas. Pfleeger, S.L (2001) Software Engineering: Theory and Practice. 2nd Ed. Prentice Hall. Botelho, M.L.A., Cunha D.F., Mendonça, F.M., Calil, S.J. (2006) Avaliacao de um sistema desenvolvido para o ensino virtual. X Congresso Brasileiro de Informatica em Saude. P.1313-1318. Florianopolis, SC. Brasil. O´Neill, K., Singh, G., O´Donoghue, J. (2004) Implementing eLearning Programmes for Higher Education: A Review of the Literature. Journal of Information Technology Education. v3, p313-322. http://jite.org/documents/Vol3/ v3p313-323131.pdf. Sigulem, D. (2000) Educacao Continuada a Distancia na Área Medica. http://www.virtual.epm.br/cursos/aulas/index.htm. Palloff, R.M., Pratt, K. (2002) Construindo comunidades de aprendizagem no ciberespaço – Estrategias eficientes para salas de aula on-line. Artmed Editora. Porto Alegre. Author: Institute: Street: City: Country: Email:

Maria Lucia de Azevedo Botelho Departamento de Ciencias Biologicas - UFTM Praca Manoel Terra Uberaba - MG Brazil [email protected]

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Biomedical Engineering and Virtual Education A. Kybartaite, J. Nousiainen, K. Lindroos, J. Malmivuo Ragnar Granit Institute/ Tampere University of Technology, Tampere, Finland Abstract— This paper briefly presents Biomedical Engineering (BME) in the virtual education. BME is a relatively new and highly multidisciplinary field of engineering. Due to its versatility and innovativeness, BME requires special learning and teaching methods. Virtual education is an emerging trend in the higher educational system. Technologies, learning theories, instructions, tutoring, and collaboration incorporated in the virtual education can lead to effective learning outcomes. European Virtual Campus for Biomedical Engineering (EVICAB) is the platform, where traditional biomedical education is transferred to the virtual. Keywords — Biomedical Engineering, Online Education, eLearning, Open Access, Collaboration.

I. INTRODUCTION Biomedical engineering (BME) is a relatively new field of engineering. It is under the process of continuous change and creation new specialty areas due to a large flow of information and advancements in technologies. Some of the well established specialty areas within the field of BME include bioinstrumentation, biomaterials, biomechanics, cellular, tissue and genetic engineering, clinical engineering, medical imaging, rehabilitation, and systems physiology [1]. The field of BME is very multidisciplinary as it brings together knowledge from many different sources, like medicine, technology and natural sciences. An education can be seen as traditional and online. The traditional education is based on teacher’s and students’ face-to-face interactions in a class. Online education has the same meaning as virtual, internet-based, web-based, or education via computer-mediated communication. It is currently becoming popular in higher educational institutions as working students are not able to spend most of their time in a class. Meanwhile, they can attain all study related material on the internet; in the place and time which is the most convenient for them. Due to its versatility and innovativeness a special educational environment is needed for BME. For this reason a common European Virtual Campus on Biomedical Engineering (EVICAB) is under the process of development.

II. TRADITIONAL

AND ONLINE EDUCATION

Despite the totally different information delivering media, traditional and online education has still much in common. Books, lecture notes, exercises, laboratory works, and final exams are common elements of any class. Nowadays it is possible to convert traditional course elements to online without content modifications or loss of data. Examples of traditional and online class elements are listed in Table 1. Although EVICAB project is in the beginning stage it already has experience in implementing the online material. The exemplary EVICAB course, Bioelectromagnetism, refers to the book which is available for students in printed and in web edited format [2]. The web book can be accessed globally, by all students at any time. Also video lectures are provided. The lecturer’s talk is recorded and compatible with alternating lecture slides. Students have the possibility to choose which lecture format to take so that their information retaining level would be the highest. The final online exam, a new dimension in learning, has also been tested. It was realized in the following way: the students attended the examination at the computer class. Their identities were checked before examination began and questions were opened on the computer. The computers were connected to the Internet and the students were allowed to use all the available material including the text books. Online examination primarily tests students’ ability to understand and make conclusions on the material. The internet examination allows instructors/ lecturers to monitor the progress of the examination via the internet independently of their location. It is not enough just to transfer the traditional material to online in order to achieve effective learning outcomes but also a pedagogical and technical support is needed as illustrated in Fig. 1. Table 1 Traditional and Online Class Elements Traditional Class: Books Lectures Laboratory works Exercises Final exam

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 329–331, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Online Class: eBooks Audio/ Video lectures Online laboratory works Online tests, quizzes Online exam

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A. Kybartaite, J. Nousiainen, K. Lindroos, J. Malmivuo

Online

Support

Lectures

Video/ Audio

Books

eBooks

Exercises

Tests, quizzes

Technologies: - ICT - VLE - Standards - Open sources

Lab works

Virtual labs

Final exams

Online exams

Traditional

Learning theories h i Course instructions Tutor/ Instructor

EVICAB Common curriculum

virtual

Common VLE Quality assurance Support for the course content production Common base for materials and technologies

Fig. 1 Traditional and online class elements, support for the material transferring and expected outcomes by implementing courses in EVICAB III. SUPPORT FOR VIRTUAL EDUCATION Technology, learning theories, course instructions, and tutors/ instructors are the key elements that support online material implementation. Traditional and online class elements, the support, and expected outcomes by implementing courses in EVICAB are illustrated in Fig. 1. In order to provide and apply the online material, sufficient information communication technologies (ICT), i.e., computers with internet access and software programs are required. A virtual learning environment (VLE), in general, is defined as software to facilitate teachers in managing educational course for students. Moodle [3] was chosen as the virtual learning environment for EVICAB courses. It serves as the common platform to all courses; the material can be accessed by teachers and students at any time. Moodle also allows tracking its users’ activity as every user can access the environment under own password. This VLE is not the only that can be used in EVICAB. If other course

providers have already implemented their materials on the other VLE, Moodle can serve as a link to that. Open source tools and open access learning materials are applied in preparing EVICAB courses. For example, when producing audio/ video lectures, accessing the material (e.g., flash players) or communicating and collaborating (e.g., Skype). So that the material prepared by different authors and tools would be compatible and possible to use within VLE, Scorm [4] standard will be applied. Lecture materials in EVICAB courses are divided into segments. Students can navigate through the whole information and choose certain parts to study. The material also can be reused and modified by adding extra information, implementing quizzes or self assessment tests. Online materials can have a disadvantage, which is passive online reading. In order to avoid that, the online education should be based on learning theories and reasonable pedagogy, like constructivism. This approach gives students the opportunity to construct their own meaning from the information presented during virtual sessions. Learning based on constructivism is seen as active, goal oriented, self-regulated, and depended on prior knowledge and experience. Every EVICAB course will have instructions so that students could know what prior-knowledge is needed, what are the requirements to pass the course, what can be expected after completing the course, and how will it be related with other courses. Based on this information students could plan their further studies with more motivation. A teacher as a physical person disappears in the virtual education as all information is available online. Thus, a role of tutor/ instructor becomes important. As students will always have questions related to the course material, assignments, practical issues, organizational matters, etc., there is a need for a contact person who can answer their questions in a short time. A direct student-to-student communication is restricted in online education. Thus, it is strongly recommended to students to communicate, collaborate, and solve common problems using any online communication technology, like discussion groups, forums, or wiki. IV. OUTCOMES This chapter outlines what outcomes have already been achieved and are expected in a long term in EVICAB. These are also illustrated in Fig. 1. Common curriculum. Since BME is a multidisciplinary field, which brings knowledge from many different sources,

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Biomedical Engineering and Virtual Education

it requires a wide educational background. EVICAB aims to create an open access common curriculum for all cycles of BME education. This is achieved by collaboration between partner institutions and universities, BME programmes. Currently, five partners are involved in curriculum development; they are represented by Ragnar Granit Institute, Tallinn University of Technology, Kaunas University of Technology, Linköping University, and Brno University of Technology. Virtual Learning Environment. EVICAB uses Moodle as the virtual learning environment. It is also the platform for tutoring and communication between students and teachers. In the future the interface will improve as more courses will be available there; more teachers and students will use VLE. High quality of online education. Since the standards for preparing and selecting the course materials are under the process of developing, the education in EVICAB has the aim to be at the highest level. This is guaranteed by quality assurance system build in EVICAB. Support for course content production. Course designers and providers are encouraged to share their experience and tools to prepare high level online materials (e.g., experience in producing video lectures, teleconferencing). Common recourses. EVICAB aims to create and maintain bases for open access lecture materials and for tools (e.g., software programs) used to create online courses. Course designers and providers could modify, improve, comment, and apply materials and tools for their need.

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promoting BME education. EVICAB will serve as the environment for that. The virtual education is a challenge both for teachers and students. The effective implementation and application of BME education in the virtual environment requires not just transferring the traditional material to the online but also efficient application of technologies, learning theories, pedagogies, human assistance and collaboration between teachers, institutions, and students. The main advantage of the virtual education is the global open access. The global learning community can be at the fingers of teachers and students. Application of learning technologies, tools, open access materials can provide a new dimension in the education and lead to effective learning outcomes.

ACKNOWLEDGMENT This work has been supported by the eLearning Programme of European Commission.

REFERENCES 1. 2. 3. 4.

Biomedical Engineering Society at http://www.bmes.org Bioelectromagnetism at http://www.rgi.tut.fi Moodle at http://moodle.org Scorm at http://www.adlnet.gov Corresponding author:

V. CONCLUSIONS The online education is a relative new approach in learning and teaching, thus it encourages collaboration for

Author: Institute: Street: City: Country: Email:

Asta Kybartaite Ragnar Granit Institute/ Tampere University of Technology Korkeakoulunkatu 10, Tampere, 33720 Finland [email protected]

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Internet Examination – A New Tool in e-Learning J.A. Malmivuo, K. Lindroos and J.O. Nousiainen Ragnar Granit Institute, Tampere University of Technology, Tampere, Finland Abstract—Internet examination is a new innovation in elearning. Internet examination extends the virtual mobility from the learning process to the examination of the students’ knowledge on the course topic. Internet examination has pedagogical benefits also in the case where the students are on the site of teaching. The paper is based on the experience we have obtained at the Ragnar Granit Institute. Keywords— e-learning, Internet.

I. INTRODUCTION Internet is more and more frequently used in education. Its benefits in distant learning and as a support in classroom learning are already widely acknowledged. We have used Internet examination in the ordinary teaching in the Institute and in the courses given by the author in other universities in Finland and abroad [1]. We apply it also in the European EVICAB project [2]. In this paper we introduce the use of Internet as a platform for course examinations and assess its benefits and drawbacks. II. FORM OF THE INTERNET EXAMINATION During the examination the students may use all the material available on the Internet, including the course book. The only thing which is not allowed is communicating with other persons with e-mail or other means. This changes the style of the questions: In ordinary examinations, where the students may not have the material available, it is more tested whether the students remember certain details from the course. In an Internet examination, where all material is at hand, the examination tests whether the students have fully understood the concepts and have the ability to combine various issues and to give rationales for their conclusions. The latter method corresponds more closely with the professional skills what the students need when they move to the working life. Depending on whether the course is part of the degree studies or supplementary education, the students participate in the examination in different way. In a degree studies examination the students take the examination in a computer class. Their identity is checked and the supervising assistant controls that the students log on the

examination with their own name. It is also important to have a list of the participating students so that no student outside the classroom may participate in the controlled examination. If the students are from several universities, the examination may be arranged in their home university at the same time provided that the aforementioned conditions are ensured. In supplementary education examination the students may take the exam anywhere because there is no need to control their identity. This is one important feature of the Internet examination. In supplementary education courses, arranged for instance in connection with international scientific congresses, the students may be from several countries and different cities and universities. Because the examination is usually arranged a couple of weeks after the course, arranging it on the course site would then be impossible for the students. III. MAKING THE EXAMINATION A. Examination style The examination may be of any form. It may include questions with multiple choice answers, calculation tasks or essays. A multiple choice examination is more suitable for tests performed during the course. In the final exam the calculation tasks or essays are more suitable. In calculation tasks the Internet examination has the problem that writing equations with the computer is more time consuming and difficult and therefore only such questions may be used where the correct result is sufficient. Deriving equations by the student to the answer is practically impossible. Writing essays is most practical from the point of view of the student. For the teacher/assistant the essays are more time consuming to check. B. Examination classroom The students make the examination in a computer classroom. They sign in the educational platform and open the examination question page. For Internet examination we have used the Moodle program [3].

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 336–337, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Internet Examination – A New Tool in e-Learning

For their answers the students open a Word file and write there their personal data and a password given by the assistant supervising the examination. The password is important to control that the examination is attended only by the students in the classroom. The students are free to use all material available on the Internet. This is good, because then they do not need to remember all details of the topic, more important is that they understand it and are able to make conclusions. We tested the Internet examination first on our course on Bioelectromagnetism. The textbook for this course is available on the Internet [4]. This form of examination tests better the students’ ability to successfully do their job in the working life. The only thing which is not allowed for the students is communicating with any other person with e-mail or any other method. An important feature in the Internet examination is that it may be performed simultaneously in more than one classroom locating in different universities in different cities or even different countries. This is important because the students do not need to travel for the examination. At the end of the examination the students upload their Word file including their answers to the Moodle system. C. Operations of the teacher Because the students will have the Internet available, the questions should not be of the style: “What is … ?” but rather of style “Why … ?” or “For what purpose … ?”. Such questions measure the students’ understanding of the topic of the question and ability to make conclusions. After the examination the teacher may download the students’ answers from the Moodle and print out them. It is easier for the teacher to review the answers because they are written with computer instead of unclear handwriting. One benefit is also that all the documentation from the examination is archived in the computer. After correcting the answers and giving the grades the teacher may upload the results to Moodle or on an Internet page for the students to see them.

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Because the students’ answers are uploaded to the server, the teacher may easily archive them. This is an additional safety factor for the student and the teacher in case the student is not satisfied to the grade given. Important is, that the teacher does not need to be in the examination location during the examination but all the administration of the examination may be performed from any location in the world where the Internet connection is available. IV. CONCLUSIONS The Internet examination is a modern way to perform the examination. Its main benefit is that it is not tied to one location but may be arranged in several different locations at the same time. The students apparently appreciate this kind of examination more for several reasons. One, but not the only one, is that all information for finding small details on the topic of the questions is available on the Internet.

ACKNOWLEDGMENT This work has been supported by the European Commission and the Ragnar Granit Foundation.

REFERENCES 1. 2. 3. 4.

www.rgi.tut.fi/edu/bem/ www.evicab.eu www.moodle.fi/evicab/moodle/ www.tut.fi/~malmivuo/bem/bembook/ Author: Jaakko Malmivuo Institute: Street: City: Country: Email:

Ragnar Granit Institute Korkeakoulunkatu 3 Tampere Finland [email protected]

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Presentation of Cochlear Implant to Deaf People J. Vrhovec1,2, A. Macek Lebar2 , D. Miklavcic2, M. Eljon2 and J. Bester2 1

MKS Electronic Systems, Rozna dolina C. XVII/22b, 1000 Ljubljana University of Ljubljana, Faculty of Electrical Engineering, Trzaska 25, 1000 Ljubljana, Slovenia

2

Abstract— We designed an Internet site for deaf people and the people who are meeting with them on an everyday bases in Slovenian language. As the native language of the deaf is the sign language, the basic information about the cochlear implant is interpreted in sign language as well. In order to understand how the cochlear implant works we first have to familiarize ourselves with our sense of hearing – the ears. The ear damages are different and according to type of injury defect aid must be different. The cochlear implant can help people who still have at least 10% of their hearing nerves preserved. After successful implantation of the cochlear implant rehabilitation is very important. Rehabilitation is crucial for distinguish the useful sound from noise and later on for distinguishing words from noise. On the designed Internet site we also included a presentation on how well deaf people with cochlear implants can hear. This part of the presentation is intended for people who can hear, so they can imagine what deaf person with a cochlear implant can hear. Keywords—cochlear implant, ear, internet site

I. INTRODUCTION In the world of silence the deaf people communicate with each other by using sign language. Sign language is there native language. When they communicate with the hearing world around them, they usually help themselves with different devices such as hearing aids and cochlear implant. In this article we will be talking about the profound deaf people and one of the devices - cochlear implant. Cochlear implant can help most of deaf people when hearing aids and drugs are not enough, yet the hearing nerve is not completely damaged. However the most important part of using cochlear implant is, that the person who is using cochlear implant, is willing to use it. Nowadays the computers are available more or less to all people. Therefore worldwide web could be an efficient way for introducing the cochlear implant to deaf people, their families and friends. The people who are interested in cochlear implant can seat behind their home computer and read the site in peace. But in which language? Problem with Slovenian deaf people is that their native language is Slovenian sign language. Deaf people in Slovenia can understand Slovenian written language, their second language, but expect from them to understand English, is not realistic.

II. METHODS A. The internet site The internet site provides presentation of information with multimedia technology. A lot of pictures are on the site to help deaf people to understand the technical terms. Because very important issue for the deaf is language, basic and also crucial explanations are also given in sign language. The rest is written down in their second languageSlovenian language. The sound presentation is for hearing people to understand, how good an average profound deaf person with cochlear implant can actually hear. The internet site can provide reading the sections that the user is interested in and read the rest in the case of lack of knowledge. The internet site was designed in Dreamweaver MX. It is divided to six different sections, as it is shown in figure 1. There is special part on the site, where user can test his/her knowledge. After the user receives the results of the test, he/she can use the link to the sections on the site. The site contains the section about the sound and the ear. After the user learns about natural hearing he/she understands easier next sections about hearing loss and one of the aids; the cochlear implant. At the end of internet content is very imported section rehabilitation. If the user wants to know more about the cochlear implant, he/she can use one of the links which point to different internet sites with similar contains.

Fig. 1 The internet site is divided to six different sections

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 332–335, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Presentation of Cochlear Implant to Deaf People

III. DESCRIPTION OF CONTENT A. Section1:Sound Sound is a disturbance of mechanical energy that propagates through matter as a wave. Sound is characterized by the properties of sound waves, which are frequency, wavelength, period, amplitude and velocity or speed. How we can hear sound is represented in the next section [9]. B. Section 2:How natural hearing works In the section about natural hearing contains the physiology of human ear. The ear consists of three basic parts - the outer ear, the middle ear and the inner ear. Each part of the ear serves a specific purpose in the task of detecting and interpreting sound. The outer ear serves to collect and channel sound to the middle ear. The middle ear serves to transform the energy of a sound wave into the internal vibrations of the bone structure of the middle ear and ultimately transform these vibrations into a compression wave in the inner ear. The inner ear serves to transform the energy of a compression wave within the inner ear fluid into nerve impulses which can be transmitted to the brain. The three parts of the ear are shown in the figure 2. The middle ear is an air-filled cavity which consists of an eardrum and three tiny, interconnected bones - the hammer, anvil, and stirrup. The eardrum is a durable and tightly stretched membrane which vibrates as the incoming pressure waves reach it. The stirrup is connected to the inner ear and thus the vibrations of the stirrup are transmitted to the fluid of the middle ear and create a compression wave within the fluid. The three tiny bones of the middle ear act as levers to amplify the vibrations of the sound wave. Due

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to a mechanical advantage, the displacements of the stirrup are greater than that of the hammer. The inner ear consists of a cochlea, the semicircular canals, and the auditory nerve. The cochlea and the semicircular canals are filled with a water-like fluid. The cochlea is a snail-shaped organ which would stretch to approximately 3 cm. In addition to being filled with fluid, the inner surface of the cochlea, in the organ of Corti, is lined with over 20000 hair cells. These nerve cells have a differ in length by minuscule amounts; they also have different degrees of resiliency to the fluid which passes over them. These nerve cells perform one of the most critical roles in our ability to hear. As a compression wave moves from the interface between the hammer of the middle ear and the oval window of the inner ear through the cochlea, the small hair cells will be set in motion. Each hair cell has a natural sensitivity to a particular frequency of vibration. The different frequencies are “heart” by different section of the organ of Corti, with the parts nearest the ossicles sensitive to high tones and the parts farthest from the ossicles sensitive to low tones [2]. C. Section 3:Hearing loss Hearing loss can be categorized by where or what part of the auditory system is damaged. There are two basic types of hearing loss: conductive hearing loss and nerve impairment. Conductive hearing loss occurs when sound is not conducted efficiently through the outer ear canal to the eardrum and the tiny bones, or ossicles, of the middle ear. Conductive hearing loss usually involves a reduction in sound level, or the ability to hear faint sounds. This type of hearing loss can often be corrected with the use of medicaments or with surgically. Very successful is the use of hearing aid. Nerve impairment occurs when there is damage to the inner ear (cochlea). Medical and hearing aids may help. Very successful is the use of cochlear implant. Nerve impairment hearing loss not only involves a reduction in sound level, or ability to hear faint sounds, but also affects speech understanding, or ability to hear clearly. The hearing loss may occur on the nerve pathways from the inner ear (retrocochlear) to the brain. That kind of hearing loss cannot be corrected with the use of medicaments or with surgically. It is a permanent loss [9]. D. Section 4:Cochlear implant

Fig. 2 The ear consists of three basic parts.

Cochlear implant is electronic device that provides useful hearing and improved communication ability to individuals who are profoundly hearing impaired and unable to achieve speech understanding with other hearing aids. For individuals with a profound hearing loss, even the most powerful

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J. Vrhovec, A. Macek Lebar , D. Miklavcic, M. Eljon and J. Bester

Fig. 4 The insert of Slovenian sign language. Fig. 3 Cochlear implant. With number 1 and 2 are marked the earhook and the processing unit. With number 3 and 4 is marked sound processor, controller option and connecting cable. The magnet is marked with number 5. Cochlear implant body is under number 6. While the most important part of cochlear implant the electrode array and electrodes are marked with number 7 and 8 [8].

hearing aids may provide little or no benefit. A profoundly deaf ear is typically the ear in which the majority of sensory receptors in the inner ear, called hair cells, are damaged or diminished [1, 3, 4, 5, 6, 8, 9]. Cochlear implant is shown in figure 3. Cochlear implants bypass damaged hair cells and directly stimulate the residual hearing nerves ends by transforming sound signal into electrical pulses, allowing individuals who are profound or totally deaf to perceive sound [1]. The most proper time for the children to receive the cochlear implant is when they reach the age between 1-2 years. Because at that age the speech development, language, and thinking skills are developing. The target audience for the developed internet site are deaf people and the people who are meeting with them on an every day base. Therefore the internet site has to be understandable and appealing to them. Deaf people talk to each other in sign language. To present them the contents in Slovenian sign language, we recorded a short movie about the main contents. The insert of Slovenian sign language is shown in figure 4. All the contents are written down in Slovenian language and corroborated with pictures. The challeneges that deaf people are faced with in every day communication and during as well as after rehabilitation are presented. For hearing people we prepared the presentation on how well can a profound deaf person with cochlear implant hear according to the results of routine hearing test. The people who can hear usually think that deaf person with cochlear implant can hear as well as he/she can. Unfortunately most profound deaf people with the cochlear implant can not hear even close to as good as we can. Therefore the sound pres-

entation was made. Well known song was filtered according to specifications that the cochlear implant has due to its construction. Obtained sound was filtered once more; the results of routine hearing test of deaf person using cochlear implant where incorporated into processing. All sound processing was made in Matlab [7]. E. Section 5:Rehabilitation After the user receives the cochlear implant the rehabilitation is very important. For young children the rehabilitation is proceeding along with child development. While older persons are once again learning to hear or they are getting used to now sense. It is on rehabilitation that depends how good the person receiving of cochlear implant would develop speech and hear the sounds around him/her. The deaf person receiving the cochlear implant can hear the sounds around him/her. He/She has then to learn to separate useful sounds from the noise. Only then can he/she learn to separate the words from the rest of the sounds. IV. CONCLUSIONS The target audience for the internet site we developed are deaf people and the people who are meeting them on everyday bases. The purpose of the internet site is to inform them how the cochlear implant works. Therefore the presentation of cochlear implant in Slovenian sign language is included. On the other hand the problems that deaf people have in everyday communication and during as well as after rehabilitation are presented. For hearing people we included the presentation how good can a profound deaf person with cochlear implant hear according to results of hearing test. The people who can hear usually think that deaf person with the cochlear implant can hear as good as he/she can. But the last is not true. Their hearing ability mostly depend on rehabilitation process.

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V. ACKNOWLEDGMENT

335 5.

The study was supported by Slovenian Research Agency and Ministry of Higher Education, Science and Technology.

6.

REFERENCES

7.

1.

2. 3. 4.

Hamida AB, M. Samet, N. Lakhouda, M. Drira and J.Mouine (1998), Sound spectral processing based on fast Fourier transform applied to cochlear implant for the conception of a graphical spectrogram and for the generation of stimulating pulses, Proceedings of the 24th Annual Conference of the IEEE Industrial Electronics Society, 1998. IECON '98, pp.1388-1393 VonBekesy G (1961), Concerning the pleasures of observing, and the mechanics of the inner ear, Nobel Lecture. Loizou PC (1999), Signal-Processing techniques for cochlear implants, IEEE engineering in medicine and biology, Vol. 18, pp.34-45. Francis A. Spelman (1999), The past, present, and future of cochlear prostheses, IEEE engineering in medicine and biology, Vol. 18 , pp 27-33.

8. 9.

Zwolan TA., Kileny PR. (1993) Cochlear implants for the profoundly deaf, Proceedings of Sixth Annual IEEE Symposium on ComputerBased Medical Systems, pp. 241-246 McDermott HJ (1998), How cochlear implants have expanded our understanding of speech perception, Proceedings of the 20th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol. 5, pp. 2251-2256 Hamida AB (2000), On the rehabilitation of Cochlear implant patients Using a Flexible and versatile speech processing technique with a spectral approach, IEEE EMBS International Conference on Information Technology Applications in Biomedicine, pp.359-364 Cochlear implant at http://www.cochlear.com/ Silva C (2005), Cochlear implants, Electrical Insulation Conference and Electrical Manufacturing Expo, pp.442-447. Author: Institute: Street: City: Country: Email:

Jerneja Vrhovec Faculty of Electrical Engineering Trzaska 25 Ljubljana Slovenia [email protected]

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New courses in medical engineering, medical physics and bio/physics for clinical engineers, medicine and veterinary medicine specialists in Serbia V. M. Spasic-Jokic1,4, D. Lj. Popovic2, S. Stankovic3 and I. Z. Zupunski4 1

2

VINCA Institute of Nuclear Sciences/Laboratory of Physics, Belgrade, Serbia University of Belgrade/ Faculty of Veterinary Medicine, Department of Physics and Biophysics, Belgrade, Serbia 3 University of Novi Sad, Faculty of Science, Department of Physics, Novi Sad, Serbia 4 University of Novi Sad, Faculty of Technical Sciences, Novi Sad, Serbia

Abstract— The paper presents new courses in medical physics, medical engineering and bio/physics for clinical engineers, medicine and veterinary medicine specialists introduced at two universities in Serbia - University of Novi Sad and University in Belgrade since 2004. The courses were aimed to educate well trained specialists in medical physics, medical engineering and veterinary medicine and to establish new programs in specialist studies incorporated in CPD programs for professional licensing. Keywords— clinical engineering, medical physics, veterinary medicine, specialist studies.

I. INTRODUCTION Following the Bologna process of transforming European educational area the new curricula in medical physics, medical engineering and bio/physics for medicine and veterinary medicine specialists in Serbia, was introduced on Belgrade and Novi Sad University starting in 2004. The new courses were aimed to fulfill the existing gap in education of physicists and medicine and veterinary medicine specialists as according to EFOMP recommendations holding a university Master’s Degree in Medical Physics, is not a sufficient qualification to work as a medical physicist or a medical engineer in hospital environment. To manage patients without supervision the Recommendations hold necessary to have basic university degree, master degree and hospital practice. Therefore, in 2004 the postgraduate program for Medical Physicists was initiated at the Association of Centers for Interdisciplinary and Multidisciplinary Studies and Research (ACIMSI), at the University of Novi Sad and in 2005 another Program of Specialist education for Medical Engineers at the Faculty of Technical Sciences, University of Novi Sad started, too. In 2006, a new program for Specialist Study for Medical Physics and Medical Engineering was established at ACIMSI, integrating other programs in the area. [1,2,3] At the same time, new courses on Bio/Physics/Medical Physics within Veterinary Medicine curricula were introduced at the Faculty of Veterinary Medicine, University of

Belgrade in 2004: those were the Core Course in Biophysics/Medical Physics and an Elective Course on Physical Methods, Instrumentation and Techniques. II. MEDICAL ENGINEERING AND MEDICAL PHYSICS A. General Medical Physicist/Engineer is generally involved in three basic hospital activities: health care services and consulting; development and research, and training. [2,3] Medical Physicist is a professional with clearly defined competences and responsibilities in health care service and consulting, patient dosimetry, development and implementation of complex equipment as well as in optimization, QA, and radiation protection. This requires adequate theoretical and practical knowledge, as well as permanent education and training. Medical (Clinical) Engineer is a professional with competences and responsibilities in health care service and consulting, patient dosimetry, technical support, development and implementation of complex equipment as well as in optimization, QA and QC procedures, and radiation protection. This also requires adequate theoretical and practical knowledge, as well as permanent education and training. B. Education and Licensing of Medical Physicists and Medical Engineers According to international recommendations of EU, EFOMP (European Federation of Organizations for Medical Physics), IFMBE (International Federation for Medical and Biological Engineering) and EAMBES (European Alliance for Medical and Biological Engineering & Science) we recognized following professional categories in Medical Physics and Medical (Clinical) Engineering: [2,3] 1.

Qualified Medical Physicist/Medical (Clinical) Engineer (QMP/QME) should have a bachelor and a master university degree and at at least 2 years’ training ex-

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 310–312, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

New courses for clinical engineers, medicine and veterinary medicine specialists in Serbia

2. 3.

perience on the job, that is essential to achieve the competencies to work as QMP Specialist Medical Physicist/Engineer (SMP/SME) must fulfill all requirements defined in point 1. and must successfully complete a 5 years CPD cycle Expert in Medical Physics/Engineer (EMP/EME) besides the requirements defined in point 2. should complete a Specialist study program and have at least 3 years of working experience, or should have a PhD degree in Medical Physics.

The certification is in responsibility of the National Certification Board, within the Ministry for Health, which forms a National Register of Medical Physicists/Engineers. The responsibility could be transferred on National Professional Society. If it is not legally possible licensing could be in competency of National Society of Biomedical Engineering and Medical Physics (BIMEF). BIMEF will be able to perform internal accreditation which could be recognized by EFOMP. Primary condition for staying in National Register is fulfilling 5 years CPD cycle. [2,3] Academic (University) education of medical physicists and medical engineers and preferences (university titles) are divided in tree basic stages: I stage – Basic University Study in Medical Physics, duration: 4 years, 240 ECT + Final thesis. University title: Medical Physicist II stage – Master University Study in Medical Physics at the Department of Physics, Faculty of Science, University of Novi Sad, duration: 1 year, 60 ECT + Master Thesis. University title: Graduated Medical Physicist –Master in Medical Physic. Master University Study in Electrical Engineering at Faculties of Electrical Engineering, duration (4+1) years, 300 (240+60) ECT + Master thesis University title: Graduated engineer- Master in Electrical and Computer Engineering III stage – Postgraduate University Study at ACIMSI (Association of Centers for Interdisciplinary and Multidisciplinary Studies and Development Researches) University of Novi Sad. Specialist study in Medical Physics, duration: 1 year, 60 ECT + Specialists thesis. University degree: Specialist in Medical Physics .Specialist study in Medical Engineering, duration: 1 year, 60 ECT + Specialists thesis. University degree: Specialist in Medical Engineering.Doctorial study in Medical Physics and Medical Engineering, duration: 3 years, 180 ECT + Doctorial thesis. University degree: PhD in Medical Physics and PhD in Medical Engineering. Postgraduate studies for medical physicists and medical engineers are organized at ACIMSI Center for Medical Physics and Clinical engineering and are complementary with similar studies in other European countries. They are

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aimed at training professional and research personnel for successful team work in medical institutions, as rapid development of medical diagnostics and therapy, as well as medical equipment of advanced technology, require a team work of experts who, apart from being competent in their profession, have to demonstrate knowledge in the field of medicine, physics and engineering. The concept of such multidisciplinary studies enables physicians, physicists and engineers, who decide to work in medical institutions, to use the existing equipment successfully, modernize it rationally and continually work on its improvement. Principal carriers of the programs are Faculty of Technical Sciences and Faculty of Sciences at the University of Novi Sad. C. Programs for Specialist Study in Medical Physics and Medical Engineering The program in Specialist Study in Medical Physics and Medical Engineering has been designed as to incorporate the contemporary scientific and professional findings in the field of medical physics, medical diagnostics and therapy as well as modern technological achievements regarding medical instruments. The curriculum offers a flexible approach to students’ preference for studying particular specialized areas of medical physics through elective subjects regarding application in current medical practice. The studies are multidisciplinary, since experts from different fields carry out the process of teaching: physicists, mathematicians, doctors, biologists, chemists, engineers and others. The educational basis are Faculty of Technical Sciences, Faculty of Sciences and Medical School of University of Novi Sad, while the clinical ones are Military Medical Academy, Belgrade and Institute of Oncology “Sremska Kamenica”. International Aspects of the Programs are recognized regarding the Bologna declaration, EFOMP (European Federation of Organizations for Medical Physics) and ESOEPE (European Standing Observatory for the Engineering Profession and Education) Programs. [1,2,3] The program offers 28 courses divided in two categories: core mandatory subjects and elective subjects. The students are recommended to choose the mentor and to select the group of subjects which is in the best correspondence with his/her job. Core subjects includes the topics in bio/physics; anatomy, physiology and cell biology; principles of biomedical engineering; medical facilities; principles and safety standards; metrology and QA programs. Elective subjects are divided in 11 groups as follows: Physiology, anatomy and cell biology; Principles of biomedical engineering; Medical facilities in radiological diagnostics and safety aspects; Medical facilities in Nuclear Medicine and safety aspects; Medical Facilities in Radiotherapy and safety aspects; Dosimetry and Radiation protection in Ra-

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diological diagnostics, Nuclear Medicine and Radiotherapy; Nonionizing techniques in medicine and safety aspects; Protection against nonionizing radiation; Metrology and mesurement uncertainty; Quality Assurance in varoius branches of medicine; and Information technologies. III.COURSES ON BIO/PHYSICS WITHIN VETERINARY MEDICINE CURRICULA

Within biomedical studies at Belgrade University, physics/and mathematics are incorporated in the curriculum at the faculties of biology, medicine, veterinary medicine, stomatology and pharmacology. For decades, physics was considered rather as sort of “cook book” of technical terms than as an essential tool for understanding and interpreting the basic laws of nature, and should it be presented as a fundamental part of today’s culture or give only elementary scientific facts and technical data for core biomedical subjects and diagnostics and therapeutic methods and instrumentation for the clinics. [5] The new program introduces in 2004 at the Faculty of Veterinary Medicine, University of Belgrade offers a Core Course in Biophysics/Medical Physics in the first year of the study and an Elective Course dealing with physical methods, instrumentation and techniques applied in veterinary medicine research and practice. The courses are aimed to reflect the interest of veterinary medicine specialist and future researchers, as well as to provide information on new physical methods and techniques to be used in biomedical sciences and practice. Their main goal is to present physics both on formal cognitive level and to instigate logical reasoning and abstract thinking, as well as to encourage future biomedical community to take a closer look into physic/biophysics /medical physics theories and methodology. The courses try to promote a new understanding of the living matter, to enabled students to observe, to categorize and to quantify the natural phenomena, to read formulae as a phenomenon or a process and not just a sequence of signs, and finally to get a grip of the totality of nature itself. [6] The Core Course titled "Selected Chapters In Physics And Biophysics In Veterinary Medicine« presents basic concepts and issues in biophysics/medical physics relevant in understanding essential physiological functions of the living systems and to present basic contemporary aspects on the transport and transformation of matter and energy, both within living and non-living environment. The Elective Course titled "Physical Methods in Veterinary Medicine Diagnostics and Therapy” is aimed to presents operative and practical knowledge on the principles and functioning of biomedical instrumentation and techniques used in veterinary medicine practice. [4,5,6]

Both courses are largely founded on practical exercises and experimental work. Mathematics workshop became an integral part of laboratory workshops and is focused on examples from clinical praxis. The syllabus is divided into modules and students are enabled to pass the course step by step, passing the test following the modules. The ex cathedra presentations are avoided as much as possible, and laboratory, video and film presentations are complementary with the theoretical part of the courses. Students are encouraged to search for literature and present seminars as a result of individual or teamwork. IV.CONCLUSIONS After two year experience of introducing new courses in medical physics, medical engineering and bio/physics for medicine and veterinary medicine specialists at the universities of Serbia, the first results are encouraging. There is strong interest among graduate at postgraduate students to apply for the new programs, as well as among professionals already working in the field. The programs, as well as the teaching stuff obtained higher evaluations for content of the courses, as well as for the clearness of presentations and good organization.

REFERENCES 1. 2. 3. 4. 5. 6. 6.

Stankovic S, Spasic Jokic V, Veskovic M (2005)Medical Physics Education in Serbia: Current State and Perspectives, Biomedizinishe Technik, Berlin, Vol.50,Supl.1/2,2005, pp.1376-1377 Faculty of Technical Science at University of Novi Sad at http://www.ftn.ns.ac.yu/studije/specijalisticke/biomedicinska.pdf ACIMSI at www.medfiz.ns.ac.yu Brown H, Smallwood RH, at al. (1999) Medical Physics and Biomedical Engineering. Inst.of Physics Publ. Bristol and Philadelphia Popovic D (2005) Courses On Bio/Physics Within Veterinary Medicine Curricula. Biomedizinishe Technik, Berlin, Vol.50, Supl.1/1, 2005, pp.40-41 Popovic D, Djuric G (1995) Teaching Physics and Biophysics for Veterinary Medicine Students In: Thinking Science for Teaching. Plenum Publ. New York, pp.423-438 Popovic D, Djuric G (1998) Physics and Mathematics In Veterinary Medicine Studies. Roskilde Univ. Press, Roskilde, Denmark, pp.194 – 202 Author: Vesna Spasic Jokic Institute: VINCA Institute of Nuclear Sciences, Laboratory of Physics (010) Street: POBox.522 City: 11001 BEOGRAD Country: SERBIA Email: [email protected]

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The Education and Training of the Medical Physicist in Europe The European Federation of Organisations for Medical Physics -EFOMP Policy Statements and Efforts S. Christofides1, T. Eudaldo2, K. J. Olsen3, J. H. Armas4, R. Padovani5, A. Del Guerra6, W. Schlegel7, M. Buchgeister8, P. F. Sharp9 1 Medical Physics Department, Nicosia General Hospital, 215 Old Nicosia Limassol Road, 2029 Nicosia, Cyprus Servei de Radiofisica I Radioproteccio, Hospital de la Santa Creu I Santa Pau, Av. Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain 3 Radiofysisk Afdeling, 54 C3, KAS Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark 4 University Hospital of the Canaries, 38320 La Laguna (Tenerife), Spain 5 SO di Fisica Sanitaria, Ospedale S. Maria della Misericordia, I-33100 Udine, Italy 6 Department of Physics “E. Fermi”, University of Pisa, Via Buonarroti 2, I-56127 Pisa, Italy 7 DKFZ, Abteilung Medizinische Physik in der Strahlentherapie, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany 8 Medizinische Physik, Universitatsklinik fur Radioonkologie, Hoppe-Seyler-Str. 3, D-72076 Tubingen, Germany 9 Bio-Medical Physics & Bio-Engineering, University of Aberdeen & Grampian Hospitals NHS Trust, Foresterhill, Aberdeen AB25 2ZD, United Kingdom

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Abstract— One of the main aims of the European Federation for Organisations of Medical Physics is to propose guidelines for education, training and accreditation programmes. This is achieved through the publication of Policy Statements and the organisation of education and training course, seminars and conferences. This is a continuous effort in an attempt to harmonise the education and training of the Medical Physicist across Europe. This paper presents an overview of the past, present and future efforts of EFOMP to achieve this aim. Keywords— Education, Training, Medical Physics, Policy Statement.

I. INTRODUCTION The European Federation for Organisations of Medical Physics (EFOMP) was set up in 1980 in London [1]. Among its aims and objectives is the proposal to issue guidelines for education, training and accreditation programmes. EFOMP’s first Policy Statement [2] was “Medical Physics Education and Training: The present European Level and Recommendations for its Future Development”, published in 1984. This Policy Statement is currently considered obsolete and a review is currently being undertaken of the status of Education and Training activities of the States of its National Member Organisations. The new Policy Statement will also take into consideration the European Union Directives relevant to Education and Training. An essential component of professionalism is Continuous Professional Development (CPD). EFOMP has been, and continues to be, very active in this area by publishing policy statements for CPD schemes and by establishing National Accreditation systems for Medical Physicists.

The exchange of information is a very important component of CPD as well as for the education and training of any professional. Therefore the support, sponsorship and organisation of educational as well as scientific meetings is another essential component of the efforts of EFOMP in advancing the professionalism of the Medical Physicist in Europe. The purpose of this paper is to give an outline of the relevant policy statements and the future plans of EFOMP in this area. II. EFOMP EDUCATION AND TRAINING ACTIVITIES A. Policy Statements In total EFOMP has published 11 policy statements and is currently preparing another two. All of them are related to the professional status of the Medical Physicist in Europe and so are relevant to the present paper. A brief description of them is given below: Policy Statement 1: “Medical Physics Education and Training: The present European Level and Recommendations for its Future Development” [2]. This policy statement was the result of an inquiry made in 1984 to the EFOMP National Member Organisations. This showed that a formally regulated additional education and training programme for physicists and university graduates in the engineering sciences with emphasis on Technological Physics existed in nearly half of all the European countries (9 from 19) that responded to the inquiry. In the remaining countries, the postgraduate on-the-job training in hospitals or Nuclear Physics sections is managed on an individual basis, i.e. not following a generally recog-

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 313–318, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

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nised nationwide scheme. This also applies to final examinations, whereby such examinations may actually be given, even in the absence of a nationwide formally regulated additional training. To qualify for postgraduate training usually requires a completed university course in physics or the engineering sciences with a certification comparable to a diploma. The length of postgraduate, on-the-job training, varies between 1 and 4 years. However, in cases where requirement is for a higher qualification in Medical Physics (e.g. 'Qualified Hospital Physicist) combined with a doctorate (Ph.D.), this period may extend to 7 years. On the average, 3 years are usually required for postgraduate on- the-job training, mostly with an average of 400 course hours. Only in 6 of 9 countries with formal postgraduate training programmes, is the additional qualification officially recognised as being comparable to that of a medical specialist. This policy statement is now considered obsolete. It remains available on the EFOMP website until the new policy statement under development is published. Policy Statement 2: “The Roles, Responsibilities and Status of the Clinical Medical Physicist” [3]. This policy statement was also published in 1984 and it concluded that the need for clinical medical physics service in each country depends primarily on the standard and scope of medical care. Generally speaking it can be said that in the radiological field (X-ray diagnostics, radiotherapy, nuclear medicine and radiation protection) there is an obvious need for a clinical medical physics service. This has been proven its development in those countries where the service has been well established. It is also obvious that the introduction of a medical physics service in general depends a great deal on the appreciation by the medical profession of the ways in which physicists may assist in solving problems of medical diagnosis and treatment. The number of physicists per million inhabitants in different European countries shows a wide variation. Figures can be used in comparisons between countries only if they have about the same standard of medical care. Countries striving to reach this standard should in their planning take into account the required medical physics service. The number of physicists needed in diagnostic radiology, radiotherapy, nuclear medicine and radiation protection is correlated to the number of institutions and the number of facilities for example, radiotherapy units. As a rule, countries at an early stage of development of medical physics are in fact developing medical physics are in fact developing medical radiation physics first as this is still the largest single aspect of the medical physics service.

EFOMP considers this strategy suitable and that it will form a basis for further development of physics service in other applications of physics to medical care. The number of clinical medical physicists and supporting staff must be adequate to meet the high standards of service required. In making such provision, health authorities are best guided by the recommendations of the national organizations that are affiliated to EFOMP. Policy Statement 3: “Radiation Protection of the Patient in Europe: The Training of the Medical Physicist as a Qualified Expert in Radiophysics” [4]. This policy statement was published in 1988 in response to Article 5 of the EEC Directive 84/466/Euratom of 3 September 1984 that state “A Qualified Expert in radiophysics shall be available to sophisticated departments of radiotherapy and nuclear medicine”. In this policy statement the Qualified Expert in Radiophysics has been defined as “an experienced Medical Physicist working in a hospital, or in a recognised analogous institution, whose knowledge and training in radiation physics are required in services where the quality of the diagnostic image or the precision of treatment is important and the doses delivered to the patients undergoing these medical examinations or treatments must be strictly controlled”. Policy Statement 4: “Criteria for the Number of Physicists in a Medical Physics Department” [5]. Published in 1991. In the opinion of the EFOMP, Medical Physics is a Health Care Profession and the Medical Physicist whose training and function are specifically directed towards Health Care is entitled to an official recognition as a specialist. High standards in Medical Physics Services are important and at a time of increasing demand sufficient resources must be directed towards an appropriate, safe and cost effective use of physical sciences in the Health Service for the benefit and safety of the patient. This policy statement defines the minimum staffing requirements of Medical Physics Departments according to the number and the sophistication of the equipment of the hospital. This policy statement has been revised and has been replaced by policy statement number 7. Policy Statement 5: “Departments of Medical Physics Advantages, Organisation and Management” [6]. Published in 1993. The recommendations of this policy statement are as follows: 1. The role of Medical Physics Departments is to support the established broad range of applications of physics and engineering in medicine and to be actively involved

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2.

3.

4. 5.

6. 7.

in the development, implementation and exploitation of new medical technologies and procedures. A main objective of a Medical Physics Department must be to provide a competent and cost-effective medical physics service to all parts of the national health services that need it. This service includes: safety of patients and hospital staff, maintenance of medical equipment and scientific support. Medical Physics services must be the responsibility of an integrated Department of Medical Physics providing an agreed core of work activities representative of the diverse character of the specialty. These services must be organized or coordinated at the highest practicable level, which can be through a regional or sub-regional structure. The Head of Department must be a physical scientist in medical physics to whom all physical scientists employed on hospital physicists' grades and technical staff must be professionally and officially responsible. The Head of Department should be responsible for the departmental budget. University Departments of Medical Physics have the further tasks of teaching, research and training in this field.

Policy Statement 6: “Recommended guidelines of National Registration Schemes for Medical Physicists” [7] Published in 1994. When EFOMP was inaugurated in May 1980, its principal objective was to harmonise and promote the best practice of medical physics in Europe. In pursuing this objective, one of the long-term aims of EFOMP is to achieve uniformly high standards of training and performance of medical physicists in the countries of all member organisations. Furthermore EFOMP wishes to see some form of recognition when these standards are achieved. This has three advantages. First, it demonstrates that patients are receiving the same level of medical physics support, no matter where they are being treated. Second, it greatly facilitates the movement of physicists from one country to another. Finally, EFOMP would be seen as the body competent to decide how the recently established qualification of European Physicist [8] will be applied in the context of medical physics. Within the European Community, the direct application of the Council Directive on "Mutual Recognition of Higher Education Diplomas" 89/48/EEC [9] has not proved a very successful mechanism for ensuring the freedom of movement and the maintenance of appropriate standards for medical physicists. A major reason for this is that the current leve1 of legalised regulation of the profession in Europe is low. However, the European Commission is

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clearly sympathetic to self-regulation by the professions and in response to an enquiry from FEANI (Fédération Européenne d'Associations Nationales d'Ingénieurs) on the Eur Ing qualification received the reply "The Commission considers that the FEANI scheme is an excellent example of self-regulation by a profession at the European level". In response to the above, in this policy statement EFOMP provides the necessary guidelines that will enable it to take the lead in establishing a mechanism for the proper recognition of medical physics by means of approved National Registration Schemes. Policy Statement 7: “Criteria for the Staffing Levels in a Medical Physics Department” [10]. Published in 1997 This policy statement is a revision of policy statement number 4 [6] and it contains more details as to how many Medical Physicists are required for a Medical Physics Department in relation to the equipment available in the hospital. Policy Statement 8: “Continuing Professional Development for the Medical Physicist” [11]. Published in 1998. Modern Health Care Services are met with everincreasing demands on competence, specialisation and cost effectiveness. The Medical Physics Service in hospital faces the same demands, and Continuing Professional Development (CPD) is vital if the Medical Physics profession is to embrace the pace of change occurring in medical practice; it promotes excellence within the profession and protects the profession and public against incompetence. CPD is the planned acquisition of knowledge, experience and skills required for professional practice throughout one's working life. Therefore EFOMP recommend that: 1. All medical physicists should be involved in CPD after qualification. 2. Formal CPD programmes should be developed to recognise individual effort. 3. Formal CPD programmes should set out clear objective guidance for the extent of CPD to be achieved within a defined timescale. 4. National organisations should have their CPD scheme included in the EFOMP Directory. 5. Renewal of professional registration should be linked to CPD performance. 6. The resources for CPD should be provided by the individual, the professional body, the employer and public education / training bodies. This Policy statement was revised in 2000 and it is replaced by policy statement number 10. Policy Statement 9: “Radiation Protection of the Patient in Europe: The Training of the Medical Physics Expert in Radiation Physics or Radiation Technology” [12]. Published in 1999.

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In order to reach harmonisation throughout Europe when implementing EC-Directive 97/43/Euratom [13] into national legislation, with regard to the definition and role of the Medical Physics Expert (MPE) EFOMP recommends the following guidelines: • • • •

•

At the minimum the MPE must have been recognised as a qualified medical physicist and preferably also have further experience. The Education and Training Scheme in Medical Physics aiming at the level of a MPE has to follow the EFOMP guidelines [4]. A system for a recognised Continuing Professional Development is recommended. According to the duties defined by the new Directive, the MPE has to be involved in radiological practices in all university and specialised hospitals using ionising radiation on patients i.e. radiotherapy, nuclear medicine and diagnostic radiology. Involvement of the MPE in radiological practices as demanded in Article 6(3) of the Directive, is recommended by EFOMP in the following way:

EC Directive: In radiotherapy the MPE shall be closely involved. EFOMP: Daily relationship between MPE and patient environment is mandatory. To be deeply involved in dosimetry, Quality Assurance and elaboration of techniques used in the radiotherapy department. EC Directive: In nuclear medicine the MPE shall be available. EFOMP: MPE shall be able to make a meaningful intervention. Daily relationship between MPE and the patient environment is most appropriate. EC-Directive: In diagnostic radiology the MPE shall be involved as appropriate. EFOMP: Depending on the spectrum of techniques used there must be access to medical physics service, for instance local or regional networks could be established to provide practitioners and smaller hospital with up to date medical physics service. When special practices are used as defined in Article 9 of the Directive, a daily relationship of the MPE and the patient environment shall be standard. Policy Statement 10: “Recommended Guidelines on National Schemes for Continuing Professional Development of Medical Physicists” [14]. Published in 2000. This is a revision of Policy Statement number 8 that further develops the recommendations for the establishment of CPD Schemes at the National Level.

Policy Statement 11: “Guidelines on Professional Contact and Procedures to be Implemented in the Event of Alleged Misconduct” [15]. Published in 2003. The role of the medical physicist in health care is diverse. In many areas the medical physicist will take decisions and give advice that have a direct influence on the management of patients and in all of them medical physicists will interact with individuals from a wide range of professional groups. This policy statement gives guidelines on professional conduct that have been drawn up to enable the National Member Organisations of EFOMP to establish a code of practice that will ensure that medical physicists across Europe conduct themselves at all times in a manner that is appropriate to the profession. Policy Statement 12: “The present Status of Medical Physics Education and Training Europe. New Perspectives and EFOMP Recommendations” [16]. Expected to be published by the end of 2007. This policy statement is still under development. The EFOMP Council is expected to approved it at its next meeting in September 2007. It will replace policy statement number 1 which is now regarded as obsolete. The organisation of the Medical Physics Education and Training in many countries has changed since the publication of the first policy statement, and more recent EFOMP Policy Statements have been issued that have introduced new concepts and new recommendations that make thorough revision of this first document necessary. EFOMP is now challenged to make recommendations for education and training in Medical Physics, within the context of the current developments in the European Higher Education Area arising from “The Bologna Declaration”, and with a view to facilitate the free movement of professionals within Europe, according to the new Directive. A complete revision of the document now therefore appears to be essential. The aim of this document is to provide an updated view of the present level of education and training in Medical Physics in Europe and make recommendations in view of these new European challenges. Policy Statement 13: “Recommended Guidelines for the Development of Quality Management Systems for Medical Physics Departments” [17]. Expected to be published by the end of 2007. This policy statement is still under development. The EFOMP Council is expected to approved it at its next meeting in September 2007. The rapid and highly sophisticated advancement of equipment and procedures in the medical field increasingly depend on information and communication technology. The safety and quality of such technology it is vigorously tested before it is placed on the market, it is not always proven to

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be of the expected level when used under hospital working conditions. To improve its effectiveness and ensure the safety of the patient and users, it is necessary to have in place additional safeguard and monitoring mechanisms. Furthermore a large number of accidents and incidents happen every year in hospitals and as a consequence a number of patients die or are injured [18, 19, 20, 21]. A contribution to these events could well be attributed to Medical Physicists (malpractice, lack of education and training, etc). This EFOMP Policy Statement outlines the way in which a Quality Management System can be developed for Medical Physics Departments, that will be instrumental in eliminating or at least minimizing the contribution of the Medical Physicist to the accidents or incidents that happen to patients while being in the hospital environment and to have the mechanisms in place to be able to use effectively and efficiently new highly complicated and sophisticated technologies and procedures.

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tional week on Radiation Protection in the Hospital Environment. European Network of Medical Physics Training Schools: This is a new initiative that is currently under development. Moving a step further from just publishing policy statements the EFOMP Officer’s have been discussing among them and have had recently discussions with other interested parties, the establishment of a process of coordinating across Europe the Continuous Professional Development Courses for Medical Physicists, so that these are harmonised and to offer the same level of education irrespective of the institution delivering them. It is anticipated that the firsts courses under this network will take place during the first half of 2008. Once the Network is established details will be available on EFOMP’s website. The Above activities are mainly organised by the Education, Training and Professional (ETP) and the Scientific (SC) Committees of EFOMP [27, 28].

B. Education and Training Activities Support for Meetings, Congresses and Courses: The sponsorship of meetings and congresses is instrumental in disseminating and encouraging the adaptation of the policy statements. EFOMP organise, co-organise, support and recognise meetings, congresses and courses with its NMOs. Guidelines that explain the above terms and the requirements for interested NMOs to collaborate in such events can be found on EFOMP’s website [22]. The purpose of these Guidelines is to help NMOs to obtain EFOMP sponsorship for their events by setting out the steps that they need to take and the conditions that must be fulfilled. The biggest event is the biennial European Congress on Medical Physics. Note that there are detailed guidelines on the requirements for this event [23]. Awards and bursaries: The encouragement of young scientists to pursue the profession of Medical Physics is of enormous importance to EFOMP. For this reason EFOMP gives awards [24] to young scientist at the EFOMP Congress and provides bursaries [25] to young scientist to attend course and participate at the European School of Medical Physics (ESMP). European School of Medical Physics: This is annual event in collaboration with the European Scientific Institute (ESI) and takes place in Archamps, France. It consists of five weeks of intensive training in Medical Physics [26]. One week each for Medical Imaging with Non-ionising radiation, Medical Imaging with Ionising Radiation, Medical Computing, Physics of Modern Radiotherapy and Brachytherapy. EFOMP is considering introducing an addi-

III. CONCLUSIONS The above brief discussion describes the activities of EFOMPS in the area of Education, Training and Professional Development of the European Physicist. These activities can only materialise through the collaboration of all the Medical Physicists of its NMOs. The NMOs must actively adopt and implement the guidelines of the policy statements as well as participate in the various events organised by EFOMP in collaboration with its NMOs. The contributions of all interested are more than welcomed in order to further develop the harmonisation of the education, training and professional status of the Medical Physicist in Europe.

ACKNOWLEDGMENT EFOMP acknowledges all those that have contributed to the development of its policy statements as well as all those that have and are organising educational and training events under its auspices.

REFERENCES 1. 2. 3.

Constitution of the European Federation of Organisations for Medical Physics, www.efomp.org/federation.html Policy Statement 1: “Medical Physics Education and Training: The present European Level and Recommendations for its Future Development”, www.efomp.org Policy Statement 2: “The Roles, Responsibilities and Status of the Clinical Medical Physicist”, www.efomp.org

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10. 11. 12.

13.

14. 15.

S. Christofides, T. Eudaldo, K. J. Olsen, J. H. Armas, R. Padovani, A. Del Guerra, W. Schlegel, M. Buchgeister, P. F. Sharp IFMBE at Policy Statement 3: “Radiation Protection of the Patient in Europe: The Training of the Medical Physicist as a Qualified Expert in Radiophysics”, www.efomp.org Policy Statement 4: “Criteria for the Number of Physicists in a Medical Physics Department”, www.efomp.org Policy Statement 5: “Departments of Medical Physics - Advantages, Organisation and Management”, www.efomp.org and Physica Medica XI(3), 1995, 126-128 Policy Statement 6: “Recommended guidelines of National Registration Schemes for Medical Physicists”, www.efomp.org and Physica Medica XI(4), 1995, 157-159 Boswell PG. Recognising Fundamentals. Europhys News 1994: 25; 46-47. Council Directive 89/48 EEC of 21 December 1988 on a general system for the recognition of higher education diplomas awarded on completion of professional education and training of at least three years duration. Official Journal of tbe European Communities 1989: 32; 16-23. Policy Statement 7: “Criteria for the Staffing Levels in a Medical Physics Department ”, www.efomp.org and Physica Medica XIII, 1997, 187-194 Policy Statement 8: “Continuing Professional Development for the Medical Physicist”, www.efomp.org and Physica Medica XIV, 1998, 81-83 Policy Statement 9: “Radiation Protection of the Patient in Europe: The Training of the Medical Physics Expert in Radiation Physics or Radiation Technology”, www.efomp.org and Physica Medica XV, 1999, 149-153 EC Directive 97/43/Euratom of 30 June 1997 on health protection of individuals against the dangers of ionising radiation in relation to medical exposures Official Journal of the European Communities No L180, 9.7.1997, p. 22 Policy Statement 10: “Recommended Guidelines on National Schemes for Continuing Professional Development of Medical Physicists”, www.efomp.org and Physica Medica XVII, 2001, 97-101 Policy Statement 11: “Guidelines on Professional Contact and Procedures to be Implemented in the Event of Alleged Misconduct”, www.efomp.org and Physica Medica XIX, 2003, 227-229

16. Policy Statement 12: “The present Status of Medical Physics Education and Training Europe. New Perspectives and EFOMP Recommendations” 17. Policy Statement 13: “Recommended Guidelines for the Development of Quality Management Systems for Medical Physics Departments” 18. Eurohealth, “Mythbusters, Myth: We can eliminate errors in health care by getting rid of ‘bad apples’”, Eurohealth, Vol. 12 No. 2, pp. 29-30. 19. Gillin, M, “Institute of Medicine Report on Medical Errors”, AAPM Newsletter, March/April, 2000. 20. International Atomic Energy Agency (IAEA). Safety Reports Series No. 17, Lessons learned from accidental exposures in radiotherapy 2000. Vienna: IAEA; 2000. 21. International Commission on Radiological Protection. Prevention of accidental exposures to patients undergoing radiotherapy. Publication 86. Exeter: Pergamon Press; 2001. 22. EFOMP support of meetings, congresses and courses: Guidelines for National Member Organisations, www.efomp.org/federation.html 23. EFOMP Congresses: Policy and General Requirements, www.efomp.org /federation.html 24. EFOMP Congress awards for young physicists, www.efomp.org/ federation.html 25. EFOMP ESMP bursaries for young physicists, www.efomp.org/federation.html 26. EFOMP European Schools of Medical Physics, www.efomp.org/ federation.html 27. EFOMP Education, Training and Professional Ccmmittee Composition and terms of reference, www.efomp.org/federation.html 28. EFOMP Scientific Committee composition and terms of reference, www.efomp.org/federation.html. Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Stelios Christofides Medical Physics Department, Nicosia General Hospital 215 Old Nicosia Limassol Road 2029 Nicosia Cyprus [email protected]

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The value of clinical simulation-based training Vesna Paver-Erzen1, Matej Cimerman2 1

University Medical Centre/ Clinical department of anaesthesiology and intensive therapy, Zaloska 7, Ljubljana, Slovenia 2 University Medical Centre/Clinical department of traumatology, Zaloska 7, Ljubljana, Slovenia

Abstract— Simulators were first used in aviation for flight training of pilots and for inter-staff communication. Regular training in the simulation centre is obligatory for all aircraft staff, whatever their rank or position. Simulation-based training has been introduced in nuclear power, space flight and petrochemical industries, particularly in the settings where there is a high probability of large-scale catastrophic events. The major advantages of learning skills on a simulator are: each procedure can be interrupted, improved and repeated until the required proficiency has been achieved, and no real harm is done when an eventual mistake –inadmissible in real clinical setting – is made on a mannequin. This learning modality is therefore less stressful for both the trainee and the teacher, and helps increase the trainee's self-confidence. Keywords— clinical training, simulation.

I. INTRODUCTION Simulators were first used in aviation for flight training of pilots and for inter-staff communication. Regular training in the simulation centre is obligatory for all aircraft staff, whatever their rank or position. Simulation-based training has been introduced in nuclear power, space flight and petrochemical industries, particularly in the settings where there is a high probability of large-scale catastrophic events. Considering that simulator-based training is wellestablished in aviation and in several other industries, it is hard to imagine that clinical skills of dealing with medical emergency situations and complications are still taught on a live patient. It has been proved that technical faults are to be blamed for only 30% of all clinical complications and that 70% are due to mistakes made by health professionals. Virtual training in resuscitation procedures was first used on unsophisticated patient mannequins. Ten years ago, simulation-based training centres for advanced medical virtual training equipped with full-scale simulators began to be set up. These »virtual patients«, who can talk and replicate all human physiological and physio-pathological functions, are used as a teaching tool for close replication of approx. 70,000 programmed clinical situations , encountered in anaesthesia and intensive care, as well as during medical and surgical interventions, resuscitation and other procedures. Simulation-based clinical training is offered in

several European university hospitals in Germany, France, Great Britain, Italy and Danemark. In the U.S.A., advancedlevel simulation traning is delivered in the so-called virtualreality hospitals, which provide close replication of all clinical situations and procedures for teaching purposes. II. WHAT ARE THE ADVANTAGES OF SIMULATION-BASED TRAINING?

There are some procedures for which standard supervised live-patient training is no longer ethically justified or acceptable to the patient. Health professionals are expected to have mastered a given procedure before performing it on a patient. Another hinderance is a limited number of patients available. Reduction in working hours of doctors in training, required under new European legislation, will result in reduced opportunity for these doctors to acquire clinical skills alongside patients. Simulation-based training has been therefore increasingly used at all levels of medical education. Simulation-based clinical skills training is provided in three domains: • • • •

psychomotor (acquiring technical skills) cognitive (decision-making) emotional (team interaction), and evaluation of performance, assessment of acquired skills.

The major advantages of learning skills on a simulator are: each procedure can be interrupted, improved and repeated until the required proficiency has been achieved, and no real harm is done when an eventual mistake – inadmissible in real clinical setting – is made on a mannequin. This learning modality is therefore less stressful for both the trainee and the teacher, and helps increase the trainee's self-confidence. As reported in the literature, medical students and doctors are positive about learning clinical skills on simulators. They find that in addition to being cost-effective, this form of learning increases their self-confidence and helps them develop a more realistic attitude toward intervening in critical situations. Doctors who acquire their clinical skills through simulation learning demonstrate lower rates of medical errors and perform various procedures more rapidly

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than their colleagues who receive standard supervised training with real patients. Despite the high costs involved in the setting up of a simulation centre, simulation-based clinical training delivered there is relatively cost-effective. Financial costs carried by a medical error which causes death or permanent invalidity of the patient are considerably higher than establishing a clinical skills learning facility. American studies have shown that costs incurred on purchasing of a high-tech simulator are returned within six months of its use. University Medical Centre Medical Council gave the green light for the establishment of a simulation centre, and set up a force group for preparatory assistance and background activities up. Simulation centre location has been chosen by Professor Sasa Markovic, Medical Director of the University Medical Centre, and plans for the reconstruction of existing facilities have been drawn up.

5.

REFERENCES

13.

1. 2. 3. 4.

Rall M, Gaba DM (2005) Chapter 84: Patient simulators. In: Miller RD ed. Miller's Anesthesia. 6th ed. Churchill Livingstone, Philadelphia, pp 3073-103. Gaba DM, Fish KJ, Howard SK (1994) Crisis management in anesthesiology. Churchill Livingstone, Philadelphia Rall M, Monk S, Mather S et al (2003) SESAM – The Society in Europe for simulation applied to medicine. Eur J Anaesthesiol 20:763 Schuttler J (2002) Anforderungskatalog zur Durchfűhrung von Simulatortraining-Kursen in der Anasthesie. Anasthesiologie & Intensivmedizin 43:828-830

6. 7. 8. 9.

10. 11. 12.

Rall M, Dieckamnn P (2005) Crisis resource management to improve patient safety. Refresher course lectures. Euroanaesthesia 2005. Vienna, Austria, 2005, pp 107-112 Dalley P, Robinson B, Weller J et al (2004) The use of high-fidelity human patient simulation and the introduction of new anesthesia delivery systems. Anesth Analg 99:1737-1741 Kuhnigk H, Kuhnigk R, Sefrin P et al (1999) »Full-scale«-Simulation in der praklinischen Notfallmedizin – Konzeption des Wurzburger Anasthesie – und Notfallsimulators. Der Notarzt 15:129-133 Gaba DM (2005) Improving patient safety by implementing strategies of high reliability organization theory. Refresher course lectures. Euroanaesthesia 2005. Vienna, Austria, 2005, pp 243-247 Kuhnigk H, Roewer N (2004) Anasthesiesimulation – Innovation fűr die Zukunft. In: Thiede A, Roewer N, Elert O, Riedmiller H eds. Chronik und Vision. Zentrum Operative Medizin 2004. Universitatsklinikum Wurzburg, Klinikum der Bayerischen JuliusMaximillians-Universitat, pp 269-270 Columbus Bussines First at http://www.meti.com/media.html Glavin R (2005) Simulation in anesthesia and acute care settings. Refresher course lectures. Euroanaesthesia 2005. Vienna, Austria, pp 155-161 Nargozian CD (2004) Simulation and airway-management training. Current Opinion in Anaesthesiology 17:511-512 The Associated Press. July 25th, 2004. Medical Training Goes Virtual at http://www.meti.com/media.html Authors: Vesna Paver-Erzen Institute: Clinical department of anaesthesiology and intensive therapy Street: Zaloska 7 City: Ljubljana Country: Slovenia E-mail: [email protected]

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A Personal Computer as a Universal Controller for Medical-Focused Appliances Denis Pavliha, Matej Rebersek, Luka Krevs and Damijan Miklavcic Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia Abstract— Modern medical-focused appliances are sophisticated devices that can process complex data and control various subsystems. This is the reason why they require a custommade advanced Graphical User Interface that is able to control all these features. In order to build such a Graphical User Interface we first need to choose a proper hardware platform and then an operating system for which we will build the Graphical User Interface application. As for the hardware, an industrial-targeted Mini-ITX mainboard meets our needs of reliability, stability and speed. The mainboard is based on the Personal Computer x86 platform and we can expand its features with peripherals such as CompactFlash card for data storage, touchscreen LCD for user interaction and an external board, connected to the USB port of the mainboard, for data interchange. The operating system used is Microsoft Windows Embedded CE in a combination with a Dynamically-Linked Library to control the features of the external USB board. With such a configuration we obtain a fast and compact controller with data interchange capability and a sophisticated Graphical User Interface. Since the Graphical User Interface is custom-made and the operating system gets loaded fast the end-user does not have a feeling to be using a PC. The main benefit is the system’s upgradeability because even with major hardware changes we can still reuse all our code to rebuild our Graphical User Interface and transfer it on a new platform without losses. Keywords— Microprocessor, Personal Computer (PC), Embedded System, Graphical User Interface (GUI), Universal Serial Bus (USB).

I. INTRODUCTION Modern medical-focused appliances have evolved into powerful machines that are based on complex electronic circuits and can perform demanding tasks at a very high speed. In addition to data processing these devices must also communicate with external peripherals and their performance has to be done at a high speed and with even higher accuracy. Therefore such devices need a sophisticated Graphical User Interface (GUI) that can deal with many parameters and process the data involved in the functioning of the appliance itself. When designing a GUI one first needs to choose a hardware platform on which the GUI will run. After revising many possible solutions we come across two possible choices, both based on a computer system. If we try to clas-

sify these computer systems into two segments regarding the sphere of usage, we can divide them into two groups [1]: • •

General purpose computers (Personal Computers), Special purpose computers (Embedded Systems).

The first segment represents Personal Computers (PCs) which are built as universal machines on which we can install an operating system and therefore use applications that are developed for this operating system. As these machines are built for general-purpose usage they are not popular as the main components of specific devices such as medical-focused equipment. However, computers matching the classification of the second segment are not intended to be used as universal. Although operating systems for such devices do exist they are in most cases on a different level than PC-based operating systems and do not provide us with all advanced features that the PC-based operating systems do. It is up to the developer to customize the operating system for the embedded system or even to develop an operating system oneself to fully satisfy the needs for the specific device. Developers of controllers have in the past predominantly used PC platforms as main system components of specific systems only if there was the need to graphically represent the data captured [3]. In most cases specifically designed microprocessor or microcontroller boards were used instead [2]. Such boards are equipped with a microprocessor or maybe a microcontroller, external memory and in most cases some specific hardware interfaces, as shown in Fig.1. Software for these solutions must be written with specific development tools that manufacturers of the microcontroller board provide and cannot be substituted by other tools. Such hardware is not upgradeable unless we replace the whole board with a board that holds a microcontroller that is a successor of the one used before. With this kind of replacement only minor changes of the software have to be made. Nevertheless, even minor software changes with a different but similar microprocessor or microcontroller can often represent a serious challenge. In this paper we suggest using a general-purpose PC as a specific-device controller with a fully featured Graphical User Interface (GUI) and capability of data interchange via an external bus.

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PRINTER

I/O

PRINTER

MONITOR

I/O

I/O

DATA PROCESSING UNIT

OPTICAL AND ACOUSTIC SIGNALS

VIDEO

(MICROPROCESSOR)

GRAPHIC PROCESSOR I/O

KEYBOARD

UART I/O

UART

~

IEEE 488

~ ~

RS 232 C

Fig. 1 A block diagram of a part of an EKG system that uses a specific microprocessor board as the main system component [2].

II. HARDWARE PLATFORM If a Personal Computer (PC) is meant to be used as a controller for such specific devices as medical-focused appliances the demands of the selected hardware are clear – reliability, stability and speed. Since our system is designed to be a controller with a Graphical User Interface (GUI) a high speed of the hardware platform is needed for the realtime control to be implemented. The stability of the system and consequently reliability are factors that cannot be let out since we can afford neither failures nor errors during the functioning of the system. For these reasons a compact Mini-ITX mainboard is used. The Mini-ITX standard was developed in 2001 by VIA Technologies and specifies a mainboard form factor with dimensions of 170 x 170 millimeters with very low power consumption [6]. Such mainboards are primarily intended for industrial usage since they are produced with a much longer sales lifetime than consumer boards. The mainboard itself already includes the microprocessor, Random Access Memory (RAM) and some basic peripherals such as the Video Graphics Array (VGA) Controller, Ethernet Controller, Universal Serial Bus (USB) 2.0 Controller and Integrated Drive Electronics (IDE) Controller. With its small dimensions, low power consumption, a long sales lifetime and the wide selection of integrated peripher-

als it represents an optimal choice as the main component of our system. Although the mainboard includes an IDE Controller it does not have any on-board storage such as Hard Disks or Flash Memory. Since the whole system has to be as compact as possible a Hard Disk would not be an optimal solution. First, Hard Disks are relatively big and would probably not fit into the small system case we plan to use and second, Hard Disks are electro-mechanical components, which makes them more susceptible for damage. Since the mainboard supports IDE devices and the avoidance of mechanical parts is welcome, a CompactFlash (CF) card proves itself as the solution. The CompactFlash (CF) card provides complete TrueIDE functionality, which means it is fully compatible with ATA/ATAPI-4 (Advanced Technology Attachment - Packet Interface) which is a computer disk drive standard [7]. This is why we can connect it directly to the IDE controller of the Mini-ITX mainboard and the CF card then acts as a Hard Disk Drive. Since there are no mechanical components involved there is no presence of mechanical delays, which additionally boosts the speed of our system. The interaction between the user and the system will be carried through a touchscreen Liquid Crystal Display (LCD). As the Graphical User Interface (GUI) will be entirely developed by ourselves we can afford to plan neither any keyboard nor pointing devices and project the whole control to be executed through the touchscreen display. This means less external peripheral devices will be needed and

PC (x86) MAINBOARD CPU

IDE

CF

VGA RAM TOUCHSCREEN

ETHERNET

DEBUGGER

USB 2.0

EXTERNAL USB BOARD

LCD

I2C GPIF

Fig. 2 A block diagram of our solution which includes a Personal Computer x86-based mainboard, some basic peripherals and an external USB board. Debugging is provided via the Ethernet interface.

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the case of the whole system will consequentially be smaller since it will not include a keyboard. As the hardware for the GUI part is already selected we still need the connective part of the system to be chosen. Although the Mini-ITX mainboards in most cases include controllers for special busses such as the Inter-Integrated Circuit (I2C) bus these controllers do not suit the needs of our appliance. What we need is a programmable GeneralPurpose Input-Output (GPIO) system. As it is not included on the mainboard an external solution is needed. The choice we made for the external bus is the USB 2.0, which is a serial bus that achieves speeds up to 480 Mbps. This is enough to satisfy the needs of our system, since it represents enough bandwidth to transfer all the data involved. The external USB board we intend to use is a Cypress CY3684 development board. Its main component is the Cypress FX2LP integrated circuit which includes a programmable 8051-based microcontroller, a General Purpose Interface (GPIF) and the I2C bus. The GPIF will be used for controlling devices that are not time critical and the I2C bus for those that are. All the interfaces are controlled by the 8051 microcontroller and thus programmable through the firmware of the board.

not even feel that he or she is dealing with a Personal Computer because the boot time is as short as on common settop-boxes 1 and the operating system appearance does not resemble typical Windows operating systems. This gives us enough space to build an application that acts as the main GUI of our system and controls all of its features. Besides this the last version of the Windows Embedded development environment named ‘Platform Builder’ can be used as a Microsoft Visual Studio plug-in. This means most of the development work can pass through the Microsoft Visual Studio, which makes it easier for developers who already have experience with this environment. The debugger data gets transferred via the Ethernet interface, as already shown in Fig.2. The hardware is supported by the operating system through a package of device drivers called a ‘Board Support Package’ or BSP. Should we want to upgrade our hardware without discarding all the work we have done so far, we simply change the BSP with another one that is specific for the new hardware and rebuild the Windows Embedded CE operating system image.

III. SOFTWARE PLATFORM After selecting the proper hardware the system now needs an operating system to handle the application processes. Even though the hardware selected is a general purpose PC we still want an operating system targeted for embedded machines and considering this demand only two choices appear – Windows Embedded or Linux Embedded. As often pointed out [4] there are many advantages of using Windows Embedded in comparison to Linux Embedded from different aspects such as costs and time to market of the project. Considering these facts Windows Embedded seems the choice to be made. In the Windows Embedded family there are two operating systems – Windows Embedded CE (formerly Windows CE .NET) and Windows XP Embedded. Since the system we are building does not need all the features of the Windows XP operating system we plan to build a Windows Embedded CE appliance. The Windows Embedded CE is a componentized operating system targeting small footprint devices [8]. The image of the whole operating system can be as small as a few megabytes. For this reason the operating system boots very quickly and the operating system image can even be loaded by the Basic Input Output System (BIOS) so that the boot time gets reduced even more. Besides this the operating system shell can get customized so that the end-user does

383

.NET application

DLL driver

DLLImport Interface

USER CODE WDAPI Object

USER CODE

.lib Module USER KERNEL WinDriver Kernel Module

Cypress EZ-USB FX2LP

Fig. 3 A block diagram that explains the interaction between different software layers [5].

The only missing driver in the Windows Embedded CE operating system is the driver for the Cypress FX2LP device. The driver should not be written as a component of the operating system but a Dynamically-Linked Library (DLL). The benefits of a DLL reflect in the possibility of being accessed from the application developed in Microsoft Visual Studio. Since driver writing is a very complex and last1

Standalone devices that connect to a signal source and display it on a television, like satellite TV receivers.

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ing project we will take advantage of a driver development toolkit named ‘Jungo WinDriver USB’. This toolkit helps us build the driver in the desired programming language and creates a diagnostic driver application we can then edit, which gives us the possibility to change the driver in the way we need it and reduces the time we would spend otherwise developing the driver from zero [5]. Such a driver is in the end a DLL file and as shown in Fig.3 can be accessed from Microsoft Visual Studio as a reference via the DLLImport2 interface. IV. CONCLUSIONS With suggested hardware configuration a generalpurpose PC is now used as an embedded system that is able to control medical-focused appliances. Even if a touchscreen LCD is included in the case with the whole system the case still remains small and compact. Since the only mechanical parts in the system are fans the risk of mechanical damage is reduced to the minimum and the compact system case can be freely moved around where and when needed. The operating system image is loaded directly by the Basic Input Output System (BIOS) and boots in a few instants, which is a big advantage in comparison to other PC-focused operating systems. The original shell of the Windows CE Embedded operating system is hidden and our custom Graphical User Interface (GUI) application is used instead. Such a configuration resembles industrial set-top-boxes and conceals the fact that a PC is used as the main component of the system. The system is standalone and able to control external appliances such as medical-focused devices via the GeneralPurpose Programmable Interface (GPIF) and InterIntegrated Circuit (I2C) interfaces that reside on the external USB board. Due to the use of an external board the compactness of the system holds back a little but it is actually an achievement since the system becomes extendable.

The main benefit of such a system is its upgradeability. If we want to change the mainboard with another one there are basically no limitations as long as we retain the use of a platform that is supported by Microsoft Windows Embedded CE and includes a Board Support Package (BSP) for this operating system. With a hardware upgrade the software does not get affected at all and we do not have to redo all the work and write either the main application or custom device drivers from the beginning. The operating system simply gets rebuilt for the new hardware platform and the application developed in .NET gets loaded on it as on the previous system.

ACKNOWLEDGMENT The authors gratefully acknowledge the Jungo Support Team for their technical support.

REFERENCES 1.

2. 3. 4. 5. 6. 7. 8.

Aksamovic A, Pasic Z, Imamovic F (2003) Selection of Processors as a Base for Development of Special Purpose Numerical Systems, Eurocon Proc. vol. 1, Eurocon 2003, Ljubljana, Slovenia, 2003, pp 118–121 Santic A (1995) Biomedicinska elektronika. Skolska knjiga, Zagreb Hinrichs H (2004) Biomedical Technology and Devices Handbook. CRC, Boca Raton Krasner J (2003) Total Cost of Development, A comprehensive cost estimation framework for evaluating embedded development platforms, Embedded Market Forecasters Jungo WinDriver User's Guide at www.jungo.com VIA Technologies at www.via.com.tw The CompactFlash Association at www.compactflash.org Microsoft Windows Embedded at www.microsoft.com/windows/embedded Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Matej Rebersek Faculty of Electrical Engineering, University of Ljubljana Trzaska c. 25 SI-1000 Ljubljana Slovenija [email protected]

2

A .NET interface used to call unmanaged DLLs from managed application code.

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Accurate On-line Estimation of Delivered Dialysis Dose by Dialysis Adequacy Monitor (DIAMON) I. Fridolin1, J. Jerotskaja1, K. Lauri1, A.Scherbakov1and M. Luman 2 1

2

Department of Biomedical Engineering, Technomedicum, Tallinn Technical University, 19086 Tallinn, Estonia Department of Dialysis and Nephrology, North-Estonian Regional Hospital, J.Sutiste Rd 19, 13419 Tallinn, Estonia

Abstract— The aim of this study was to compare equilibrated urea Kt/V (eKt/V) from the slope of the logarithmic online UV-absorbance measurements measured by the Dialysis Adequacy Monitor (DIAMON), by eKt/V obtained from a new algorithm that can be implemented into the DIAMON prototype. As the reference the urea eKt/V was utilized obtained from the blood samples according to the rate adjustment method. The mean value of equilibrated Kt/V obtained with UV-absorbance (eKt/Va) was 1.06 ± 0.21, using the new algorithm (eKt/Vn) was 1.09 ± 0.18, and eKt/V from blood-urea (eKt/Vb) 1.09 ± 0.20 (N = 21). The mean values of eKt/V were not statistically different comparing different methods. However, both the systematic and the random error were diminished by the new algorithm. The systematic error was decreased from 2.19% to 0.312%, and the random error was decreased from 14.37% to 7.30% using the new algorithm. In summary, the DIAMON prototype can accurately and on-line estimate the dialysis dose. Keywords— hemodialysis, dialysis dose, dialysis quality, dialysis monitoring, absorbance.

I. INTRODUCTION The dialysis dose has been reported to have a great significance for the outcome of the dialysis treatment [1], [2]. On-line monitoring of the dialysis dose has been suggested as a valuable tool to ensure adequate dialysis prescription [3]. A new technique for on-line monitoring of solutes in the spent dialysate utilising the UV- absorbance has been established, enabling one to follow a single hemodialysis session continuously and monitor deviations in dialysis efficiency [4]. A good correlation between UV-absorbance and a small removed waste solute such as urea enables the determination of Kt/V for urea [5]. Recently a new prototype device - Dialysis Adequacy Monitor (DIAMON), has been designed for continuous, online, estimation of delivered dialysis dose. The monitor that is small and simple to handle, is based on the UV-technique and replaces the scientific-work oriented spectrophotometer in clinical practice. A new algorithm was developed to ensure accurate on-line estimation of delivered dialysis dose by means of Kt/V applied successfully on to data acquired by a spectrophotometer during the clinical experiments [6].

The aim of this study was to compare DIAMON equilibrated urea Kt/V (eKt/V) from the slope of the logarithmic on-line UV-absorbance measurements, by a new algorithm developed to calculate eKt/V, and the urea eKt/V obtained from the blood samples according to the rate adjustment method [7]. II. PATIENTS This study was performed after approval of the protocol by the Tallinn Medical Research Ethics Committee at the National Institute for Health Development, Estonia. An informed consent was obtained from all participating patients. Ten uremic patients, three females and seven males, mean age 62.6 ± 18.6 years, on chronic thrice-weekly hemodialysis were included in the study at the Department of Dialysis and Nephrology, North-Estonian Regional Hospital. Three different polysulphone dialysers were used: F8 HPS (N=11), F10 (N=2), and FX80 (N=8) (Fresenius Medical Care, Germany) with the effective membrane area of 1.8 m2, 2.2 m2, and 1.8 m2, respectively. The dialysate flow was 500 mL/min and the blood flow varied between 245 to 350 mL/min. The type of dialysis machine used was Fresenius 4008H (Fresenius Medical Care, Germany). III. MATERIALS AND METHODS Dialysis machine

Dialysate inlet

Dialysate outlet

Patient DIAMON prototype To drainage

Fig. 1 Schematic clinical set-up.

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eKt/V from the three methods was finally compared regarding mean values and SD. Also random error was calculated for different methods as SD over the sessions’ Accuracy. For a single session Accuracy was in percentage as

Accuracy =

Kt / Vb − Kt / Va *100% Kt / Vb

(1)

where eKt/Vb and eKt/Va are the eKt/V values from blood-urea and from UV-absorbance, respectively. The new algorithm eKt/Vn was used instead of eKt/Va when Accuracy was calculated for the New model. Systematic error and random error were calculated as the mean value and as SD over the total material Accuracy. Student’s t-test (two tailed) and Levene Test of Homogeneity of Variances were used to compare means for different methods and SD values respectively. Fig. 2 Dialysis Adequacy Monitor (DIAMON) during the clinical experiments

The mean value of equilibrated Kt/V obtained with UVabsorbance (eKt/Va) was 1.06 ± 0.21, using the new algorithm (eKt/Vn) was 1.09 ± 0.18, and eKt/V from blood-urea (eKt/Vb) 1.09 ± 0.20 (N = 21 for all methods) (Fig. 1). The mean values of eKt/Va, eKt/Vn and eKt/Vb were not statistically different (P ≥ 0.27). The SD-s were not significantly different (P ≥ 0.38) for any methods. Fig. 4 shows the difference for single dialysis treatments between observed eKt/Vb using the Present model and the New model respectively. The difference is obviously decreased using the New model.

1,5

1,0

eKt/V

The clinical set-up of the experiments is shown on Fig. 1. An optical dialysis adequacy sensor was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through the optical cuvette. The optical dialysis adequacy sensor consisted of a Dialysis Adequacy Monitor (DIAMON) (AS Ldiamon, Estonia) that was used for the determination of delivered dialysis dose (Fig. 2). DIAMON incorporated a light source (280nm UV LED), a detector (GaNi UV-photodiode), an electronic circuit board, and an optical cuvette. The monitor was connected to the fluid outlet of the dialysis machine with all spent dialysate passing through during the on-line experiments. The transimitted light intensity of the spent dialysate was measured. The sampling frequency was set to 20 samples per minute. The obtained intensity values were processed to obtain UV-absorbance and presented on the computer screen by a PC using Ldiamon’s software (AS Ldiamon, Estonia, for Windows). The results from measurements during 21 hemodialysis treatments using a LED with a peak emission wavelength of 280±5 nm are presented in this paper. The algorithm to calculate eKt/V as described earlier was used [5] (referred as “Present model”). The new algorithm (“New model”) to calculate eKt/V was obtained using regression analysis including several dependent parameters like slope of the logarithmic on-line UV-absorbance, ultrafiltration volume, dialysis length, blood flow rate, dialyzer’s urea clearance in-vitro, patient’s dry body weight, and two dummy variables gender and indication for diabetes [8].

IV. RESULTS

0,5

0,0

Present

New

Blood

Fig. 3 Predicted eKt/Vb using the Present model (Present), the New model (New), and the observed eKt/Vb (Blood).

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I. Fridolin, J. Jerotskaja, K. Lauri, A.Scherbakovand M. Luman

V. DISCUSSION

0.30 0.20 0.10 0.00 0.50

0.70

0.90

1.10

1.30

1.50

-0.10 -0.20 eKt/Vb-new model eKt/Vb eKt/Vb-eKt/Va_Diamon

-0.30

eKt/Vb

Fig. 4 Differences between the observed eKt/Vb and predicted eKt/Vb using the Present model (eKt/Va_Diamon) and the New model respectively.

Systematic +/- Random Error, %

Fig. 5 shows the Systematic and the random error for Present and New model using blood urea eKt/V as a reference. The systematic error was 2.19% for eKt/Va and 0.312% for eKt/Vn. The systematic error, being relatively small before the new algorithm was applied, decreases even more for New model. The random error using blood urea eKt/V as a reference was 14.37% for eKt/Va and 7.30% for eKt/Vn. The random error is decreased essentially being significantly different (P < 0.05) for the Present and the New model. As seen from the results the prediction of eKt/Vb can be done much more precisely applying the New model.

20,0 15,0 10,0 5,0 0,0 -5,0

The mean values of eKt/Va, eKt/Vn and eKt/Vb were principially all the same (Fig. 3). This means that the new prototype device - Dialysis Adequacy Monitor (DIAMON), based on the UV-technique, can estimate reliably the delivered dialysis dose by means of eKt/V. Fig. 4 shows the difference for single dialysis treatments between observed eKt/Vb using the Present model and the New model respectively. The difference is obviously decreased using the New model with possibilities to apply a correction in order to achieve higher accuracy. Fig. 5 shows that both the Systematic and the random error for Present and New model using blood urea eKt/V as a reference decrease for the New model. The results are confirmed by the fact that the new algorithm has been successfully applied to the eKt/V estimated by a commercial spectrophotometer [6]. This means that utilizing the new algorithm the eKt/Vb can be predicted with good results in terms of the Systematic and the random error. The parameter values are comparable with the specifications given to other available dialysis adequacy monitors [9]. The DIAMON prototype is small, does not interfere with dialysis machine’s operation, and is based on the UV-method which does not need blood samples, no disposables or chemicals, is fast, and allows to follow a single hemodialysis session continuously and monitor deviations in dialysis efficiency. New algorithm should be applied to the data material not included into the model build up to proof further the validity of the model. This can be done by creating a model using only a part of the data material and validating the obtained model on the rest of the material. Preferably the material used to validate the model should include new set of values for the model parameters which did not exist during the model build-up (e.g. new patients, dialyse filters, etc.). Including new patients should be the most sensitive because of the possible different composition of the UV-absorbing compounds filtered from the blood into the dialysate during the dialysis. In summary, utilizing eKt/V from the DIAMON prototype the overall dialysis dose can be estimated with satisfactory accuracy and precision. To validate the algorithm with data material not included into the model build up will be issue in the further studies.

-10,0

VI. CONCLUSIONS

-15,0

Present vs Blood

New vs Blood

Fig. 5 The systematic and the random error for Present and New model using blood urea eKt/V as a reference.

The presented results show the possibility to estimate urea eKt/V with a high accuracy utilizing the new algorithm based on on-line UV-absorption measurements in the spent

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Accurate On-line Estimation of Delivered Dialysis Dose by Dialysis Adequacy Monitor (DIAMON)

dialysate with the DIAMON prototype. More general eKt/V validation using the UV-technique should be validated in the next studies.

ACKNOWLEDGMENT The authors wish to thank Galina Velikodneva for assistance during clinical experiments, Aleksander Frorip and Rain Kattai for skilful technical assistance and also those dialysis patients who so kindly participated in the experiments. The study was supported by the Estonian Science Foundation Grant No 5871 and 6936, by the NATO Reintegration Grant EAP.RIG 981201, and by the LDI Inc. Enterprise Estonia project.

REFERENCES 1. NKF K/DOQI guidelines. CLINICAL PRACTICE GUIDELINES FOR HEMODIALYSIS ADEQUACY, UPDATE 2006. at http://www.kidney.org/professionals/KDOQI/guideline_upH D_PD_VA/index.htm. 2. Port F K, Ashby V B, Dhingra R K, Roys E C, and Wolfe R A (2002) Dialysis dose and body mass index are strongly associated with survival in hemodialysis patients. Journal of the American Society of Nephrology 13:1061-1066 3. Locatelli F, Buoncristiani U, Canaud B, Khler H, Petitclerc T, and Zucchelli P (2005) Haemodialysis with on-line monitor-

4.

5.

6.

7. 8. 9.

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ing equipment: tools or toys? Nephrology Dialysis Transplantation 20:22-33 Fridolin I, Magnusson M, and Lindberg L-G (2002) On-line monitoring of solutes in dialysate using absorption of ultraviolet radiation: technique description. The International Journal of Artificial Organs 25:748-761 Uhlin F, Fridolin I, Lindberg L-G, and Magnusson M (2003) Estimation of delivered dialysis dose by on-line monitoring of the UV-absorbance in the spent dialysate. American Journal of Kidney Diseases 41:1026-1036 Fridolin I, Uhlin F, Magnusson M, and Lindberg L-G (2006) Accurate Estimation of Delivered Dialysis Dose by On-Line Ultra Violet Absorbance in the Spent Dialysate. Nephrol Dial Transplant. Vol 21:ERA/EDTA XLIII Congress (abstract), Glasgow Daugirdas J T (1995) Simplified equations for monitoring Kt/V, PCRn, eKt/V, and ePCRn. Advances in Renal Replacement Therapy 2:295-304 Fridolin I and Uhlin F, 'Device for Dialysis Quality Parameters, Utility Model nr. EE 00620 U1. Estonia, 2006. Fresenius, OCM. Online Clearance Monitor. Operating instructions for 4008 H7S Dialysis Machines, Fresenius Medical Care 2000. Author: Ivo Fridolin Institute: Department of Biomedical Engineering Technomedicum Tallinn University of Technology Street: Ehitajate tee 5 City: 19086 Tallinn Country: Estonia Email: [email protected]

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Ambulatory blood pressure monitoring is highly sensitive for detection of early cardiovascular risk factors in young adults Maja Benca, Ales Zemva, Primoz Dolenc Division of Hypertension, University Medical Centre, Ljubljana, Slovenia Abstract— We evaluated the appropriateness of 24-h ambulatory blood pressure (BP) monitoring to detect prehypertensive conditions in apparently healthy siblings of patients with premature cardiovascular disease (CVD). We performed office blood pressure measurements and 24-hour ambulatory blood pressure monitoring in 30 young adults (mean age 26 ± 3 years), whose parents have experienced premature CVD, and 30 control subjects (mean age 26 ± 3 years) with a negative family history of CVD. Positive parental CVD history group had significantly higher mean values of 24-h systolic BP (123 ± 10 mm Hg vs. 118 ± 6 mm Hg; p = 0.044), daytime systolic (127 ± 12 mm Hg vs. 121 ± 7 mm Hg; p = 0.041) and diastolic BP (77 ± 8 mm Hg vs. 73 ± 4 mm Hg; p = 0.045) as well as 24-h heart rate (71 ± 8 beats/min vs. 67 ± 8 beats/min; p =0.05) and systolic BP load (21 ± 20% vs. 10 ± 11%; p = 0.02) compared to controls. There was no significant inter-group difference in blood pressure measurements obtained by conventional office method. In addition, the study group had a considerably higher diurnal variability of blood pressure and heart rate, which is believed to be contributing to their overall CVD risk. In conclusion, slightly higher levels of blood pressure, blood pressure variability and heart rate are early determinants of higher CVD risk, which can be detected in individuals by using 24-h ambulatory blood pressure monitoring. Keywords— ambulatory blood pressure monitoring, blood pressure variability, young adults, office blood pressure.

I. INTRODUCTION Accurate measurement of blood pressure is essential to classify individuals, ascertain their blood pressure-related risk as well as to guide treatment of hypertensive patients. It is known that 24-hour ambulatory blood pressure monitoring gives a better prediction of risk than office blood pressure measurements and is useful for diagnosing certain specific clinical conditions, like white-coat hypertension [1,2]. We investigated whether 24-hour ambulatory blood pressure monitoring is also a suitable method for detecting individuals at higher risk among apparently healthy young adults. In a cross-sectional study we compared a group of 30 young adults with a positive parental history of premature cardiovascular disease (CVD) to a sex and age-matched group of controls. We

hypothesized that the positive parental CVD group would have in average higher arterial blood pressure and higher blood pressure load. II. METHODS A. Subjects The study group consisted of 30 young adults, age 18 – 31 years, whose parents (at least one of them) have experienced some form of a premature CVD (myocardial infarction, stroke or venous thrombosis). Prematurity of CVD meant manifestation of disease before the age of 55 years for male parents and 65 years for female parents. In the control group, there were 30 sex and age-matched young adults with a negative parental CVD history. The age of their parents was at least 55 or 65 years (for fathers and mothers respectively) or older. The basic characteristics of both groups are presented in Table 1. Table 1 General characteristics of study and control group Variable

Study Group

Number (males/females) Age (years) Body mass index (kg/m²)

Control Group

Pvalue

19/11

19/11

1.00

26.2 ± 3.2

26.2 ± 3.0

0.97

24.6 ± 5.0

22.8 ± 3.6

0.13

A written informed consent was obtained from all the participants. The study was previously approved by the Medical Ethics Committee of the Ministry of Health of Slovenia. B. Basic measurements All the participants attended laboratory in the morning, between 7.30 and 8.30 a.m., after night fasting. Their body weight was measured to the nearest 0.1 kg and body height was measured barefoot to the nearest 0.01 m. Body mass index was calculated as body weight in kg divided by square height in m².

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C. Office blood pressure measurements Office systolic and diastolic blood pressures were measured by conventional auscultatory method, performed by trained and experienced person using a calibrated mercury sphygmomanometer. The procedure was done according to well known recommendations – subjects were previously instructed not to consume alcohol, caffeine or nicotine prior to test, comfortably seated at the room temperature, with legs uncrossed, cuff placed on a relaxed and supported arm, such that the middle of the cuff on the upper arm is at the level of the right atrium [1]. D. Ambulatory blood pressure monitoring Measurements of ambulatory 24-hour blood pressure and heart rate were performed by Spacelabs Medical Inc. 90207 ambulatory blood pressure monitors (Redmond WA, USA), which passed the validation testing as recommended by the British Hypertension Society and the US Association for the Advancement of Medical Instrumentation [3]. Monitor uses the oscillometric technique, which is less susceptible to the changes of transducer position over the brachial artery and to the external noise, but still requires from subject to be at rest while the measurement is proceeding. The device, consisting of an appropriate cuff placed on a non-dominant upper arm and connected by a tube to a small monitor attached to a subject's belt, was prepared and activated by a trained technician. All the participants received oral and written instructions on how to act while the measuring is being done, as well as how to react in case of discomfort. Measurements were taken every 20 minutes during daytime and every 30 minutes during night-time over a 24-hour period, preferably on a workday. Data were later analyzed using software package developed by our institution. Following the exclusion of artefactual readings, we analyzed the following statistical parameters: daytime systolic and diastolic pressure and heart rate, night-time systolic and diastolic pressure and heart rate, 24-hour systolic and diastolic pressure and heart rate, as well as systolic and diastolic blood pressure load [13]. Blood pressure load was defined as the percentage of total correctly recorded measurements over 24 hours, that were >140/90 mmHg during awake hours and >120/80 mmHg during asleep hours [2]. The program also provided a plot of the data. E. Statistical analysis Results were statistically analyzed using software package SPSS for Windows – version 11.0. At first, means of descriptive statistics were used for comparison

Maja Benca, Ales Zemva, Primoz Dolenc

between the groups. We investigated the parameters of interest (24-hour BP monitoring results) using independent t-tests. A p-value of ≤ 0.05 was considered statistically significant. III. RESULTS Ambulatory monitoring showed that positive parental CVD history group had significantly higher mean 24-hour systolic and diastolic, mean daytime systolic and diastolic, and mean systolic and diastolic blood pressure load. Daytime and 24-hour heart rates were also significantly higher in this group. However, mean values of systolic and diastolic pressure, measured by conventional technique did not differ significantly between the groups. Data are presented in the Table 2. Individuals with a positive parental CVD history (study group) also had significantly higher degree of variability of several blood pressure and heart rate parameters. Variability is seen as standard deviation in Table 2. Table 2 Blood pressure and heart rate parameters, expressed as mean value ± standard deviation) Legend: BP = blood pressure, SBP = systolic blood pressure, DBP = diastolic blood pressure, HR = heart rate.

Variable Office BP (mm Hg) SBP DBP 24h ambulatory BP

Study Group

Control Group

125 ± 13 78 ± 12

123 ± 12 76 ± 9

0.653 0.410

123 ± 10 73 ± 7

118 ± 6 70 ± 4

0.044 0.076

127 ± 12

122 ± 7

0.041

77 ± 8

73 ± 4

0.045

113 ± 9

110 ± 7

0.147

65 ± 6

63 ± 6

0.252

21 ± 20 11 ± 15

10 ± 11 6±6

0.020 0.077

71 ± 8

67 ± 8

0.050

76 ± 9

70 ± 9

0.020

62 ± 8

61 ± 6

0.597

pvalue

monitoring

24h SBP (mmHg) 24h DBP (mmHg) Daytime SBP (mmHg) Daytime DBP (mmHg) Night-time SBP (mmHg) Night-time DBP (mmHg) SBP load (%) DBP load (%) 24h HR (beats/minute) Daytime HR (beats/minute) Night-time HR (beats/minute)

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Ambulatory blood pressure monitoring is highly sensitive for detection of early cardiovascular risk factors in young adults

IV. DISCUSSION Our study confirmed that parental history of premature cardiovascular diseases in young adults is indeed related to significantly higher values of arterial blood pressure and blood pressure load, compared to control subjects of same age. It is an early indicator of promoted atherosclerosis, which in this case can easily be explained by interplay of genetic code and individual's environment. Both factors are known to commonly pass on from parents to siblings. The heritability of blood pressure has already been proven on twin-pairs as on general population [4,5]. The age of young adulthood of our participants was chosen in order to detect very early changes in cardiovascular system, which appear in prehypertensive period, when blood pressure is just beginning to rise but is still within normal range. Thus, we presume it is less likely that target organs in those subjects had already been damaged. In older subjects, long lasting blood pressure elevations eventually cause several secondary changes, like established atherosclerosis or nephroangiosclerosis that tend to raise blood pressure additionally. In this way, our study enlightened another important clinical application of ambulatory blood pressure monitoring – evaluation of pressure related risk in young, apparently healthy people, whose history or other data reveal enhanced probability of premature cardiovascular events. Until today, most common application of ambulatory blood pressure monitoring was diagnostic, such as identifying individuals with white coat hypertension, non-dipping blood pressure pattern, patients with refractory hypertension, suspected autonomic neuropathy, and patients in whom there was a large discrepancy between clinic and home blood pressure measurements [1,2]. Several prospective studies have documented that the average level of ambulatory blood pressure predicts risk of morbid events better than office blood pressure [1,6]. However, research is rarely performed on young and healthy adults. Majority of studies were performed on patients, treated for hypertension or other chronic diseases [7,8]. Most of important prospective or cross-sectional studies on CVD risk factors in children or young adults used conventional, office blood pressure measurements, which are less reliable in comparison to 24-hour ambulatory blood pressure measurements [9-12]. Thus, the usage of ambulatory blood pressure monitoring is the main advantage of our study. Finally, we detected a higher degree of blood pressure and heart rate variability among the subjects of study group. The occurrence of blood pressure fluctuations over time has been documented since the 18th century, but the clinical importance of this phenomenon is only now being

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recognized [13]. Reports of several studies indicate that diurnal blood pressure variation, in addition to high blood pressure per se, is related to target organ damage and the incidence of cardiovascular events [14]. One of the first important researches to demonstrate a significant increase in cardiovascular mortality with an increase in blood pressure and heart rate variability in general population was the Ohasama study [15]. In the Pamela study, which investigated a sample of 3200 individuals, randomly selected from the general population, scientists found a significant positive relationship between left ventricular mass index and 24-hour average blood pressure values. They also provided the first demonstration of a positive independent association between left ventricular mass index and blood pressure variability [16]. Some reports suggested that vascular hypertrophy is the first damage to appear as a consequence of increased blood pressure variability [14]. Early vascular hypertrophy is best revealed by ultrasound measurement of intima-media thickness of large arteries, preferably carotid arteries. Well known European ELSA study proved that not only average 24-h pulse pressure and systolic BP values, but also 24-h BP fluctuations are associated with, and possibly determinants of, the alterations of large artery structure in hypertension [17]. These findings opened some new fields for research. In the future, it will be necessary to answer the questions about the prognostic relevance of blood pressure variability [18] and treatment possibilities for modulation of 24-h blood pressure profiles [19,20]. Ambulatory blood pressure monitoring will undoubtedly be the main investigating method in the increasing number of studies that will try to answers these questions. Whether ambulatory blood pressure monitoring will predominantly stay a scientific method, or it will be accepted as a diagnostic tool for a wider range of clinical indications remains to be seen. Although it is a noninvasive and usually painless method, ambulatory blood pressure monitoring demands a fulltime, 24-hour compliant behavior of patients or healthy volunteers, which makes it less convenient for a routine screening test. Another important limiting factor is the financial aspect, since the cost of procedure is substantially higher compared to the office blood pressure measurements. V. CONCLUSION Ambulatory blood pressure monitoring is more reliable in detection of early, preclinical elevations of blood pressure compared to the office blood pressure measurement. 24-h blood pressure levels, as well as degree and pattern of its diurnal variability have important implications for long term

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morbidity and mortality. Devices for ambulatory blood pressure measurement are usually sold with software packages that present the data in variety of ways. It would facilitate the practice if the graphic presentation of the data was standardized, as is the case for electrocardiograms.

9. 10. 11.

ACKNOWLEDGEMENT The study was supported by grant from Slovenian Research Agency.

REFERENCES 1.

2. 3.

4. 5. 6. 7. 8.

Pickering TG, Hall JE, Appel LJ et al. (2005) Recommendations for blood pressure measurements in humans and experimental animals; Part 1: Blood pressure measurement in humans; A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on high blood pressure research. Hypertension 45: 142-161. Dolenc P: Neinvazivno 24-urno merjenje krvnega tlaka. In: Dobovisek J, Accetto R. (2004) Arterijska hipertenzija. 5th edition, Lek, Ljubljana, 75-97. O'Brien E, Coats A, Owens P et al. (2000) Use and interpretation of ambulatory blood pressure monitoring: recommendations of the British Hypertension Society. BMJ 320: 1128-1134. Snieder H, Harshfield GA, Treiber FA. (2003) Heritability of blood pressure and hemodynamics in African- and EuropeanAmerican Youth. Hypertension 41: 1196-1201. Kupper N, Willemsen G, Riese H. (2005) Heritability of daytime ambulatory blood pressure in an extended twin design. Hypertension 45: 80-85. Weber MA. (2002) The 24-hour blood pressure pattern: does it have implications for morbidity and mortality? Am J Cardiol 89(suppl): 27A-33A. Kennedy BP, Farag NH, Ziegler MG et al. (2003) Relationship of systolic blood pressure with plasma homocysteine: importance of smoking status. J Hypertens 21: 1307-1312. Sundstrom J, Sullivan L, D'Agostino RB et al. (2003) Plasma homocysteine, hypertension incidence, and blood pressure tracking; The Framingham Heart Study. Hypertension 42: 1100-1105.

12. 13. 14. 15. 16. 17.

18. 19. 20.

Primatesta P, Falascheti E, Poulter NR. (2005) Birth weight and blood pressure in childhood; Results from the Health survey for England. Hypertension. 45: 75-79. Alper AB, Chen W, Yau L et al. (2005) Childhood uric acid predicts adult blood pressure; The bogalusa heart study. Hypertension 45: 34-38. Thomas NE, Baker JS, Davies B. (2003) Established and recently identified coronary heart disease risk factors in young people. The influence of physical activity and fitness. Sports Med 33(9): 633-650. Pall D, Katona E, Fulesdi B et al. (2003) Blood pressure distribution in a Hungarian adolescent population: comparison with normal values in the USA. J Hypertens 21: 41-47. Parati G. (2005) Blood pressure variability: its measurement and significance in hypertension. J Hypertens 23 (suppl 1): S19-S25. Parati G, Lantelme P. (2002) Blood pressure variability, target organ damage and cardiovascular events. J Hypertems 20: 1725-1729. Kikuya M, Hozawa A, Ohokubo T et al. (2000) Prognostic significance of blood pressure and heart rate variabilities. The Ohasama Study. Hypertension 36: 901-906. Sega R, Corrao G, Bombelli M et al. (2002) Blood pressure variability and organ damage in a general population. Results from the PAMELA Study. Hypertension 39: 710-714. Mancia G, Parati G, Hennig M. (2001) Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) J Hypertens 19: 19811989. Parati G, Valentini M. (2006) Prognostic Relevance of Blood Pressure Variability. Hypertension 47: 137-138. Palatini P, Parati G. (2005) Modulation of 24-h blood pressure profiles: a new target for treatment? J Hypertens 23: 1799-1801. Kario K. (2005) Morning Surge and Variability in Blood Pressure: A New Therapeutic Target? Hypertension 45: 485-486. Address of the corresponding author: Ales Zemva Division of Hypertension, University Medical Centre Bolnisnica dr. Petra Drzaja Vodnikova 62 1525 Ljubljana Slovenia E-mail: [email protected]

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Application of time-gated, intensified CCD camera for imaging of absorption changes in non-homogenous medium. P. Sawosz, M. Kacprzak, A. Liebert, R. Maniewski Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences Trojdena 4, 02-109 Warsaw, Poland

Abstract— The paper presents application of time-gated, intensified CCD camera for imaging of local changes of absorption in the non-homogenous liquid phantom. The surface of the phantom was illuminated sequentially at 25 points (forming 5×5 array) by laser beam at wavelength of 780 nm generated by picosecond, near-infrared diode laser. The spatial distribution of diffusely reflected photons was measured in reflectance geometry at null source-detector separation. For each position of the laser beam the reflectance was measured for two different time windows, distinctly delayed in respect to the laser pulse. The observation of late photons, which penetrated deeply in the optically turbid medium allowed to image the absorbing inclusion (10 mm diameter black ball) located at depth of 15 mm. For each of two time windows the single images for all scanned points were summed. Obtained final images allowed to localize the non-homogeneity in the phantom. The study shows, that the presented method based on imaging at null source-detector separation distance for late time windows may be applied in the evaluation of the tissue absorption measurements, especially in the brain oxygenation imaging. Keywords— time-gated intensified CCD camera, timeresolved imaging, non-homogenous medium

I. INTRODUCTION In the last years the optical techniques based on near infrared spectroscopy were rapidly developed in medical diagnostics, especially in brain studies [1]. These techniques are non invasive and potentially could be easily applied in clinical conditions at the bedside. Large number of emission and detection points positioned on the surface of the head allows to image changes of brain oxygenation and/or perfusion and finally to localize the ischemic areas. Several technical solutions of the optical systems for imaging of brain oxygenation changes were proposed. Continuous wave [2-6], frequencydomain [7, 8] and time-domain [9-14] systems were reported. Recently, time-gated CCD camera was applied in construction of the NIR imager as a multichannel detector [15,16]. Imaging on the CCD array with application of intensified, timegated camera was proposed for positioning of absorbing and scattering inclusions [17] as well as fluorescent objects [18] in a turbid medium. This imaging technique could potentially increase spatial resolution of the optical methods by combining the information of spatial and temporal distribution of photons remit-

ted from an object of interest. Such measurement technique can also be used for imaging at null source-detector separation for improving the spatial resolution and contrast [19,20]. In the present paper we report on experiment in which temporal and spatial distribution of photons reemitted from a highly scattering turbid medium, simulating human tissue was imaged at null source-detector separation. This experiment is a first step in planned development of a brain oxygenation imaging system based on the time-gated ICCD. II. EXPERIMENTAL SETUP The experimental setup for measurement of time-resolved spatial distribution of diffuse reflectance from a turbid medium, simulating human tissue consisted the ICCD camera, diode laser, delay line and non-homogenous liquid phantom. Phantoms was fish tank filled with milk and water solution with absorbing inclusion, black ball of diameter of 10 mm immersed at depth of 15 mm. The position of the ball is marked in Fig.1. Near-infrared, picosecond diode laser BHL-600 (Becker&Hickl, Germany) at wavelength of 780 nm and repetition frequency of 50 MHz was applied. The pulse width was about 100 ps. To acquire pictures at different times in respect to the laser pulse we used time-gated intensified CCD camera Picostar HR (Lavision, Germany).

Fig. 1. Setup for measuring time-resolved spatial distribution of diffuse reflectance (1. scanning grid, x – position of black ball, 2. non-homogeneity black ball, 3. Nikon standard 50mm objective, 4. ICCD camera, 5. Becker&Hickl near-infrared, picosecond diode laser, 6. trigger line).

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 410–412, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Application of time-gated, intensified CCD camera for imaging of absorption changes in non-homogenous medium.

The phantom was illuminated sequentially at 25 different points as it is shown in Fig.1 (scanning grid), however the optical pathlength was constant for all positions. For each position of the laser beam, the camera grabbed the images for two different time windows. The time windows 300ps long were delayed in respect to the laser pulse for 1100 ps and 1400 ps. The CCD data collection time was 1280 ms. The data from the camera was acquired with the use of a PC class computer (Pentium IV, 3.30 GHz) and DaVis software v.7.0 provided by the ICCD manufacturer (LaVision. Germany). The 12bit images of 320×240 pixel resolution were recorded. The time between the laser pulse and opening of the camera shutter was changed using delay line (Kentech Instruments, UK). The change of delay time was controlled with a RS232 communication line and took about 350ms. III. RESULTS The spatial distribution of diffusely reflected light after its penetration in the highly scattering phantom was measured. Time-resolved experiment allowed us to distinguish photons with respect to their pathlength. However during experiment we focused at time windows, which were significantly delayed in respect to the laser pulse. We summed up 25 images corresponding to each of two time windows. Resulting images are presented in Fig. 2 and Fig. 3, for earlier and later time window respectively.

411

IV. DISCUSSION The presented experiment showed that the measurement of spatially and temporally-resolved diffuse reflectance from a highly scattering turbid medium is feasible. We observed only late photons, therefore we could increase the sensitivity of the camera to the changes of absorption located deeply and we imaged successfully the non-homogeneity disturbance, immersed at depth of 15 mm. For the earlier time window the black spot, which corresponds with the position of the ball is more focused. However, it can be noted that for the later time windows the contrast between homogenous and non-homogenous areas is higher. Unfortunately this technique has also disadvantages, which need to be taken under consideration. Primarily numerical aperture of such system is limited and the switching time between delays is significant comparing to the hemodynamic changes. We conclude that the method based on imaging at null source-detector separation distance for late time windows may be applied in development of brain oxygenation imaging system.

REFERENCES 1.

Fig. 2 Resulting image delayed by 1100 ps in respect to the laser pulse.

Fig. 3 Resulting image delayed by 1400 ps

in respect to the laser pulse.

Litscher, G. and G. Schwarz (1997) Transcranial cerebral oximetry. Pabst Sci. Pub. Lengerich. 2. Siegel, A.M., J.J.A. Marota, and D.A. Boas (1999) Design and evaluation of a continuous-wave diffuse optical tomography system. Optics Express. 4(8): p. 287-298. 3. Boas, D.A., et al. (2001) The accuracy of near infrared spectroscopy and imaging during focal changes in cerebral hemodynamics. Neuroimage. 13(1): p. 76-90. 4. Franceschini, M.A., et al. (2003) Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near-infrared optical imaging. Psychophysiology. 40(4): p. 548-60. 5. Yamashita, Y., A. Maki, and H. Koizumi (1999) Measurement system for noninvasive dynamic optical topography. Journal Of Biomedical Optics. 4(4): p. 414-417. 6. Kohl-Bareis, M., et al. (2002) Near-Infrared Spectroscopic Topographic Imaging of Cortical Activation. Lecture Notes of ICB Seminar on Laser Doppler Flowmetry and Near Infrared Spectroscopy in Medical Diagnosis, Warsaw. 7. Chance, B., et al. (1998) A novel method for fast imaging of brain function, non- invasively, with light. Optics Express. 2(10): p. 411-423. 8. Danen, R.M., et al. (1998) Regional Imager for Low-Resolution Functional Imaging of the Brain with Diffusing Near-Infrared Light. Photochemistry and Photobiology . 67(1): p. 33-40. 9. Eda, H., et al. (1999) Multichannel time-resolved optical tomographic imaging system. Review Of Scientific Instruments. 70(9): p. 3595-3602. 10. Miyai, I., et al. (2001) Cortical mapping of gait in humans: a near-infrared spectroscopic topography study. Neuroimage. 14(5): p. 1186-92. 11. Selb, J. (2005) et al., Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system: analytical model and experimental validation. J Biomed Opt. 10(1): p. 11013.

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412 12. Kacprzak, M., A. Liebert, and R. Maniewski (2005) A time-resolved NIR topography system for two hemispheres of the brain, in European Conferences on Biomedical Optics. Munich, Germany. 13. Wabnitz, H., et al. (2006) Depth-selective analysis of responses to functional stimulation recorded with a time-domain NIR brain imager, in Biomedical Optics 2006 Technical Digest (Optical Society of America, Washington, DC). p. ME34. 14. Contini, D., et al. (2006) Design and characterization of a twowavelength multichannel time-resolved system for optical topography. Biomedical Optics Technical Digest (Optical Society of America, Washington, DC). 15. Selb, J., et. al. (2006) Time-gated optical system for depth-resolved functional brain imaging Journal of Biomedical Optics 11(4), 044008 (July/August) 16. Selb, J., et. al. (2005) Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system:analytical model and experimental validation, Journal of Biomedical Optics 10(1), 011013 (January/February) 17. D'Andrea, C., et al. (2003) Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera. Journal Of Physics D-Applied Physics. 36(14): p. 1675-1681.

P. Sawosz, M. Kacprzak, A. Liebert, R. Maniewski 18. Laidevant, A., et al. (2006) Time-Resolved Imaging of a Fluorescent Inclusion in a Turbid Medium Using a Gated CCD Camera. in Biomedical Optics 2006 Technical Digest (Optical Society of America, Washington, DC). Fort Lauderdale, Florida, USA. 19. Sase, I., et. al. (2006) Noncontact backscatter-mode near-infrared time-resolved imaging system: preliminary study for functional brain mapping, Journal of Biomedical Optics 11,(5), 054006 (September/October) 20. Torricelli, A., et. al. (2005) Time-Resolved Reflectance at Null Source-Detector Separation:Improving Contrast and Resolution in Diffuse Optical Imaging, PRL 95, 078101

Author: Piotr Sawosz Institute: Institute of Biocybernetics and Biomedical Engineering PAS Street: Ks. Trojdena 4 City: Warsaw Country: Poland Email: [email protected]

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Bluetooth Portable Device for Continuous ECG and Patient Motion Monitoring During Daily Life P. Bifulco1, G. Gargiulo2, M. Romano1, A. Fratini1 and M. Cesarelli1 1

Biomedical Engineering Unit – Dept. of Electronic end Telecommunication Engineering, University "Federico II", Naples, Italy 2 The University of Sydney: Electrical and Information Engineering school, Sydney, Australia

Abstract— Continuous patient monitoring during daily life can provide valuable information to different medical specialties. Indeed, long recording of related cardiac signals such as ECG, respiration and also other information such as body motion can improve diagnosis and monitor the evolution of many widespread diseases. Key-issues for portable or even wearable biomedical devices are: power consumption, longterm sensors, comfortable wearing, easy and wireless connectivity. Within this scenario, is valuable to realize prototypes making use of novel electronic technologies and common available communication technologies to assess practical use of long-term personal monitoring and foster new ways to provide healthcare services. We realized a small, battery powered, portable monitor capable to record ECG and body three-axes acceleration and continuously wireless transmit to any Bluetooth device including PDA or cellular phone. The ECG front end offers ultra-high input impedance allowing use of dry, long-lasting electrodes such conductive rubbers or novel textile electrodes that can be embedded in clothes. A small size MEMS 3-axes accelerometer was also integrated. Patient monitor incorporate a microprocessor that controls 12-bit ADC of signals at programmable sampling frequencies (e.g. 100 Hz) and drives a Bluetooth module capable to reliable transmit real-time signals within 10 m range. All circuitry can be powered by a standard mobile phone like Ni-MH 3.6V battery that can sustain more than seven day continuous functioning utilizing the Bluetooth Sniff mode to reduce TX power. At the moment we are developing dedicated software to process data and to extract concise parameters valuable for medical studies. Keywords— Personal monitoring device, ECG, 3-axes accelerometer, Bluetooth, biomedical instrumentation.

I. INTRODUCTION For the management of various pathologies it can be very important to monitor patient for long periods during his normal daily activities [1-3]. For example, a continuous personal monitoring of chronic patients can reduce hospitalisations and improve patients’ quality of life; cardiac long monitoring (e.g. ECG) can help in diagnosis and identification of syncope and other paroxysmal arrhythmias; longterm patient’s activities monitoring can help in elderly people management; combining cardiac activity (e.g. heart rate)

and body-motion, patient’s physical activity and energy expenditure can be estimated [4]; human performance in particular condition and/or environment (e.g. athletes, divers) can be evaluated, etc. It is also worth mention that continuous monitoring can help in drive and regulate therapies and treatment (e.g. monitor blood glucose and insulin injection control). To accomplish these tasks personal patient’s monitoring equipment have to comply with some specific requirement: reduced dimension, portability and/or wearability (light weight, specific sensors, body compatibility etc.), long-term signals or parameters monitoring (battery consumption, long-term electrodes, etc.), continuous signal acquisition and real-time processing and feature extraction (A/D, microprocessors, SW, etc.), transmission capability (band, range, wireless, etc.), provide data integrity and security (communication protocols, identification, encryption, etc.), compliance with medical devices regulation (electrical safety, electromagnetic compatibility, etc.) [7]. Recently are becoming more and more available on market wireless monitoring devices, such as hospital patient monitors, ambulance or portable equipments, some homecare devices and, more in general, devices to be used in the every-day life, which often use available telecommunication channels to communicate with external environment. Beside, the spread of personal computational devices such as mobile phone and PDA, embedding wireless communication technology, offers a great advantage in making patient monitoring devices truly personal, and truly wearable. In particular, Bluetooth standard [8-10] offers important advantages: operation in ISM (Industrial, Scientific and Medical) band, low cost, low EM interferences [11], reduced power consumption, confidentiality of the data, dimensions of the transmitter and it is capable of generate small pico-net of some devices. Also it is embedded in most of portable, palm computers and mobile phones and already used in a great number of wearable devices (e.g. mobile phones wireless headsets). The emerging Zig-Bee standard [12] offers enhanced capabilities especially in term of power consumption, number of connected devices, etc. but, currently, it is not so widespread as Bluetooth. Taking into account the mentioned requirements, a small prototype personal monitor, capable to record one or more ECG leads, body 3-axes acceleration, and an optional photo-plethismograph (PPG)

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has been realized and tested in different environments. A C++ software provides signal processing and plots; this SW can be ported on PDA or mobile phones. II. MATERIALS AND METHODS A. ECG monitoring Long term body-potentials monitoring requires specific solutions. In particular, electrodes stability over time it is crucial [5]: use of wet electrodes (e.g. commonly Ag/AgCl disposable electrodes, also employed in Holter ECG recording) is to avoid because of progressive drying of conductive gel. An alternative can be the use of polarizable electrodes (e.g. platinum) or dry electrodes such conductive rubbers, easily tolerated by skin, flexible and, for that, often utilized in sport medicine and long-term recording. The latter, however, offer higher impedance with respect to others, which imply higher input impedance for the amplification stage. Furthermore, novel design made available textile electrodes that can be embedded in clothes, which significantly improve daily usability; this solution may result again in high electrode impedance. In addition to that it is worth remind that electrode current generates overpotentials. These considerations suggest keeping amplifier input- impedance as higher as possible [6]. Another significant problem, especially in daily life recordings, is electrode motion artifact. It is well known that unstable connection between electrode and skin, but also skin stretch and in general motion cause relatively large electrode potential variations, which degrade bio-potential recording quality. Obviously, as also above mentioned, another key issue is circuit power consumption: it have to be kept as limited as possible to improve cell duration. We decided to supply our circuit using a common Ni-MH 3.6V battery (as those commonly use for mobile phones): a capacity of 1000 mAh is usual. Accordingly to these considerations, a ECG frontend was designed to provide a very high input impedance (obtaining also a general independence from the electrode used), a gain of about 1000 V/V, current consumption < 1 mA, single power supply of 3.6V, over voltage protection, large dynamic and opportune monitoring-ECG frequency band. B. Body motion To get concise information about patient motion to estimate physical activity a novel MEMS (MicroElectroMechanical Systems) 3-axes accelerometer was employed. MEMS technology is based upon micromachined sense elements, usually silicon, to create moving

structures. Mechanical properties of silicon (stronger than steel but only a third of the weight) combined with microelectronics allow electrical signal generation by the moving structures. Typically a MEMS accelerometer consists of interlocking fingers that are alternately moving and fixed. Acceleration is sensed by measuring the capacitance of the structure, which varies in proportion to changes in acceleration. A capacitive approach allows several benefits when compared to the piezoresistive sensors used in many other accelerometers. In general, gaseous dielectric capacitors are relatively insensitive to temperature. Although spacing changes with temperature due to thermal expansion, the low thermal coefficient of expansion of many materials can produce a thermal coefficient of capacitance about two orders of magnitude less than the thermal resistivity coefficient of doped silicon. Capacitance sensing therefore has the potential to provide a wider temperature range of operation, without compensation, than piezoresistive sensing. Moreover, most of the available capacitive sensors allows for response to DC accelerations as well as dynamic vibration. These characteristics of MEMS capacitive accelerometer sensor combined with their extremely tiny dimension (few mm) and light-weight (few grams), their low power consumption made such sensors a convenient choice for personal biomedical devices design. C. Photo-plethismograph and temperature sensor Photoplestismographic (PPG) and Sp02 sensors are nowadays integrated in most of patient monitors. The use of light (red and infrared) throughout patient’s skin to estimate changes in artery diameter that in turn depend on blood pressure provides a non invasive way to gather information such as heart rate, percentage of oxygenated hemoglobin and qualitative data about blood pressure. However, such type of sensors result very sensitive to motion and usually require relatively high power consumption. Integrated temperature sensors provide a reliable, intrinsically linear voltage (or current) proportional to temperature, absorbing extremely low currents; uncalibrated sensors usually offer accuracy of tens of degree. Such sensors (few mm in dimension) can be easily integrated with other circuitry and can provide information about patient’s skin temperature, which in turn depends on local peripheral circulation muscle activity, etc. D. Signal acquisition and transmission Modern microcontrollers can easily perform channels multiplexing, analog to digital conversion, data packet and transmission stack protocol formation and can also drive RF circuitry. In order to resolve small signal variation a 12bit

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ECG ECG

A/D A/D

… MUX

3-axes accel.

12 12bit bit

… other sensors analog inputs

Microprocessor Microprocessor

Serial comm.

TX bluetooth

memory memory

Fig. 1 Personal monitor device: blocks schematic AD converter was employed. An integrated, commercially available, Bluetooth transmitter have been utilized: it operates at a frequency of 2.4 GHz (ISM band), the antenna is integrated on circuit board and allow 10 meters operative range. However, Bluetooth transmitter in normal functioning mode draws a relatively high current (about 50 mA) from batteries reducing their life to few hours of continuous transmission. A solution can be a temporary storage of data into internal personal device memory and intermittent data transfer, obtaining a good compromise of real-time data transfer, by using a Bluetooth power saving modality. Bluetooth offers three different current-saving modes: the Hold mode, Sniff mode and Park mode (see Bluetooth specification). In sniff mode, a slave is only active periodically; during the active phase, slave can receive and send data as usual. The master, knowing the active phase interval, only addresses the slave during this period; this explains the lower current consumption required. Of course, the possible bit rate is also reduced due to the pause time. Global architecture of the realized device is depicted in the following block schematics

Fig. 2 Picture of the realized circuit of patient monitoring device on market. Power supply of all circuitry was regulated to 3.3V. Bluetooth module current consumption was about 40 mA which be lowered down to 6 mA using the Sniff mode power saving modality, still allowing a continuous transmission of 10 kbps. The following figure show the entire circuit realized (PPG excluded) compared with one-cent coins. Circuit sizes are 20 by 43 by 5 mm. Software was designed to continuously receive data from the Bluetooth personal monitor. Following figures show the raw signals received (5m distance): color code is: ECG (blue); latero-lateral axis accel. (cyan); accel. anteroposterion axis accel. (green); acceleration caudo-cranial axis acceleration (red); PPG (purple), when available. Dry silicon rubber electrodes were used in most of the recordings. Due to the extremely high input impedance some recordings were successfully performed with patient immerse in water (not the transmitter!), using rough elastic bands with thin copper wires embedded as electrodes.

III. RESULTS Features of the different modules of the realized prototype device are here reported. ECG front end show the following characteristics: input impedance: >1014Ω; CMMR: 90 dB; gain: 730 V/V; bandwidth: 0.38-43 Hz; noise 0.1-10 Hz: 5μVpp; power supply: 3.3V; supply current: 1mA. MMA7260Q by Freescale MEMS accelerometer was used to measure 3-axes acceleration (range ±1.5g), frequency response from DC (gravity is measured) to 200 Hz, power supply: 3.3V; supply current:0.5mA max. Also a photopletismograph and an IC temperature sensor were assembled and optionally added to the realized devices. The signal ADC and the Bluetooth transmission module were acquired

Fig. 3 Example of raw signals received from a standing patient

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IC samples. Special thanks goes to Prof. A. Luciano for helpful discussions and suggestions.

REFERENCES 1.

Fig. 4 Example of raw signals received from a patient performing a series of squatting physical exercises (3 cycles are evident on accelerations)

IV. DISCUSSION AND CONCLUSIONS A small, battery powered (standard mobile phone cell), portable monitor capable to record ECG and body threeaxes acceleration and continuously wireless transmit (10m range) to any Bluetooth device including PDA or cellular phone was realised. The ECG front-end offers considerably high input impedance allowing a sort of electrode type independence (dry, long-lasting electrodes such conductive rubbers were used). A small size MEMS 3-axes accelerometer was also integrated. At present we are adapting the software to be executed on PDA and mobile phones. Also new SW features are being included to process data and to extract concise parameters valuable for medical studies (e.g. HRV, respiration rate extraction from ECG, physical activity, body position, etc.). In particular, estimation of body standard positions (upright, supine, prone, etc.) and activities (walking, running, sleeping) is being developed. Trials employing of textile sensors and device modification to be integrated in wearable systems are scheduled. Further studies are being started to adapt the device to monitor patient during sleep, athletes and to record fetal ECG. Other researches will be concentrates on evaluating different sensors (such as blood pressure, glucose, etc.), in order to design personal monitors for specific pathologies or for targeted studies.

ACKNOWLEDGMENT

A. Fratini, P. Bifulco, M. Bracale, M. Cesarelli. (2005) A prototype wireless personal ECG monitoring device connected via Bluetooth. IFMBE Proc. vol. 11, 3rd European Medical & Biological Engineering Conference, Prague, Czech Republic, Nov. 20-25, 2005. 2. Degree thesis n. 355 by A. Fratini (2005) ‘Bluetooth Patient wireless telemetry’ Biomedical Eng. Unit - D.I.E.T. University "Federico II" of Naples. 3. Degree thesis n. 378 by G. Gargiulo (2006) ‘Design and development of a prototype for continuous acquisition and processing of biomedical signals’ Biomedical Eng. Unit D.I.E.T. University "Federico II" of Naples. 4. Strath SJ, Brage S, Ekelund U (2005) Integration of physiological and accelerometer data to improve physical activity assessment. Med Sci Sports Exerc. 37(11 Suppl):S563-71 5. Searle A and Kirkup L. (2000) A direct comparison of wet, dry and insulating bioelectric recording electrodes. Physiol. Meas. 21:271-283 6. Scheer HJ, Sander T and Trahms L (2006) The influence of amplifier, interface and biological noise on signal quality in high-resolution EEG recordings. Physiol. Meas. 27: 109-117 7. Lin YH, Jan IC, Ko PC, Chen YY, Wong JM, Jan GJ (2004) A wireless PDA-based physiological monitoring system for patient transport.. IEEE Trans Inf Technol Biomed. 8(4):43947 8. SIG Bluetooth, (2001) ‘Specification of the Bluetooth System - Core’ version 1.1, February 2001 9. J.Bray, C.Sturmann, “Bluetooth: Connect without cables”, Prentice Hall 10. Bluetooth, The official bluetooth website: http://www.bluetooth.com 11. COMAR – Technical Information Statement (2000) Human exposure to radio frequency and microwave radiation from portable and mobile telephones and other wireless communication devices 12. ZigBee Alliance at http://www.zigbee.org Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Paolo Bifulco University ‘Federico II’ of Naples Via Claudio, 21 (I-80125) Napoli Italy [email protected]

Author gratefully tanks Analog Device, Burr-Brown, Freescale Semiconductor, Maxims, which kindly to provide

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Clinical implication of pulse wave analysis R. Accetto1, K. Rener1, J. Brguljan-Hitij1, B. Salobir1 1

University Medical Center Ljubljana, Division of Hypertension, Ljubljana, Slovenia

Abstract— Conventional blood pressure measurement can not explain the link between hypertension and cardiovascular diseases. The missing link is arterial stifness wich can be meassured by noninvasive applanation tonometry. Although well known fenomenon, due to techological reasons it was not clinicaly used for diagnostic purposes. With computer and other technology we are able do detect and analize periferal pulse wave and central aortic pulse wave. Central aortic pulse wave is a function of arterial stifness. The process, by wich the arterial system interacts with left ventricle and coronary arteries can be demonstrated by analysing aortic root pressure waveform. In the young it is common to see no or small augmentation in contarst to older person. Examlpes are presented.

is simple to use, noninvasive and accurate method. The principal of applanation tonometry is partially compression of artery agains hard structure. The small sensor detects the force on the artery wall (2,3). We are using applanation tonometer produced by Sphygmocor (Fig 1.)

Keywords— Pulse wave, applanation tonometry.

I. RISK FACTORS Cardiovascular diseases are one of the main causes of death in western industrial countries as in Slovenia. The exact etiology is not known but we know that a growing number of risk factors including hypertension, diabetes, smoking, dislipidemia etc. lead to heart atacs, heart failure and stroke. Blood pressure is usualy measured by noninvasive auscultatory method introduced by Riva-Roci nad Korotkow more that 100 years ago, and newer oscilometric method. With these methods we are measuring the arterial pressure in brachial artery, since we are using upper arm cuff. The registration of the arterial pulse was used for clinica diagnosis in mid to late nineteenth century and first description of changes in the shape of pulse with age were described (1). The link between risk factor and cardiovascular disease is arterial stifness. It can be increase by three mechanisms: 1. A breakdown of elastin fibres 2. Damage to the endothelium/smooth muscle mechanism 3. An increase in mean arterial pressure The process, by wich the arterial system interacts with left ventricle and coronary arteries can be demonstrated by analysing aortic root pressure waveform. II. APPLANATION TONOMETRY The development of the hand-held tonometry probe means revival of pulse wave analysis in clinical practice. It

Fig. 1. Applanation tonometer

The Sphygmocor system incorporets the actual pulse recorded at the radial artery and the properties of the transfer functiom between the aorta and the radial artery to estimate central aortic pressure. The radial wave form is calibrated using systolic and diastolic pressures values from conventional cuff measurements. An average waveform is calculated from the ensemble average of a series of contigous pulses (4,5) III. AORTIC PRESSURE WAVEFORM The shape of aortic pressure pulse is a result of the ventricular ejection and the physical properties of the arterial system. Normaly, there is wave reflection. In the absence of wave reflection, the shape of the pressure wave during systole is determined by the ejection wave and the elastic and geometric properties of the ascendenting aorta. If wave reflection occures during systole, it will increase the pressure agains wich the ventricle has to eject blood. Knowledge of the pressure waveform will facilitate analysis of the coupling between the ejecting heart and the pressure load (Fig 2.)

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 354–356, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

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Fig. 4: Pulse wave analysis in older woman (RT 74 years) (Klinični oddelek za hipertenzijo, 2007)

Fig. 2. Pulse wave characteristics P1: first systolic ejection, P2: the systolic peak, ΔP: augmentation pressure, LVET: left ventricular ejection time

Difference between P1 and P2 is absolute augmentation and augmentation index can be calculated, related either to P1 or pulse pressure (systolic blood pressure – diastolic blood pressure). Stifness of arteries has major effect on aortic pulse wave. In the young it is common to see no or small augmentation as seen on Fig. 3 in contast to older person (Fig. 4.)

In younger person the radial peak is narrow, the late systolic shoulder in aortic pulse is lower than the early systolic peak. In older person there is increased late systolic shoulder in radial pulse and increased late systolic augmentation in the aortic pulse. Augmentation pressure during systole produces a different loading patteren on the miocardium, even if peak systolic values are identical.

IV. CONCLUSIONS Applanation tonomertry is noninvasive method for detecting and analysing pulse wave. By detecting periferal (radial) pulse wave, central aortic pulse wave can be calculated. Despite the same radial pulse wave, the central aortic palse wave can be different, influenced by age, hypertension, diabetes and other risk factors wich influence on arterial stiffness.

REFERENCES

Fig. 3.Pulse wave analysis in young woman (KR 30 years) (Klinični oddelek za hipertenzijo, 2007)

1. Mohamed. FA. The physiology and clinical use of the sphygmograph. Medical Time Gazette 1872;1:62 In: A clinical guide. Pulse wave analysis. SphygmoCor. Sidney, Australia 2006 2. Nichols WW, Orourke MF. McDonald´s Blood flow in arteries. Theoretica, experimental and clinical principles. 1998, 4th edition. Arnold, London 3. Kelly R, Hayward C, Avolio A et al. Non-invasive determination of age related changes in the human arterial pulse. Circulation 1989;80:1652-1659

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356 4. Karamanoglu M, Orourke MF, Avolio P et al. An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur Heart J 1993;14:160-7 5. Chen CH, Fetics B, Nevo E et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation 1997;95(7):1827-36

R. Accetto, K. Rener, J. Brguljan-Hitij, B. Salobir Author: doc. dr. Rok Accetto, dr. med. Institute: University Medical Centre Ljubljana, Division of Hypertension Street: Vodnikova 62 City: SI-1000 Ljubljana Country: Slovenia Email: [email protected]

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Control Abilities of Power and Precision Grasping in Children of Different Ages B. Bajd and L. Praprotnik University of Ljubljana, Faculty of Education, Ljubljana, Slovenia Abstract— The aim of our study was to assess the grip force control under visual feedback in children of three age groups. We designed a tracking-based assessment system. The gripmeasuring device developed was used as an input to a tracking task where the children applied the grip force according to the visual feedback from the computer screen. The evaluation was performed in a group of healthy 6, 9, and 14- year old children. In our investigation we used three different target signals: randomized ramp, sinus, and rectangular signals. The children performed the tasks using the lateral grip precision and cylindrical power grip of their dominant hand. The results show that the relative root mean square error (rrmse) between the target and the measured response was noticeably decreased with increased age. The results showed no significant differences in performance between the precision and power grip. Keywords— human hand, power grip, precision grip, motor development

I. INTRODUCTION Grasping is defined as the application of functionally effective force of the hand to an object to accomplish a task within given constraints [1]. When an object is grasped, the fingers have to apply forces that satisfy functional constraints of the task and physical constraints of the object. The key goal in most grasping tasks is to maintain a stable grip by adapting the contact forces of the fingers and the hand. Based on the functional properties of the task, grip types can be divided based on the functional properties of the task into precision and power grips [2]. When the emphasis of the task is on strength and stability of the object, power grips are used (e.g. holding a hammer). The object is grasped between the fingers and palm to achieve high stability and to prevent slippage. Precision grips are used when high dexterity and manipulability of the grasped object is required (e.g. grasping a pencil). In precision grip the object is grasped between the tips of the thumb and the opposing fingers, providing high compliance and tactile feedback during manipulation. An important factor affecting grasping of an object is tactile sensing of the force applied by the fingertips and other parts of the hand. During grasping finger forces are controlled by the central nervous system which regulates the activity of the hand and arm muscles to act in synergy. The

central nervous system receives dynamic feedback information from the visual sensors and from other exteroceptive and proprioceptive body sensors while regulating the motor output. The development of sensory-motor functions shaping the hand skills begins in human at nursery age. Voluntary grasping develops at 4 months of age and the first precision grasping appears at the age of 10 months [3,4]. Grasping and manipulative skills further develop in subsequent years. The sensory and motor functions are enhanced during the childhood until they become fully developed. In our previous research we assessed the grip force control in the group of 10-year old children and the group of adults. The results of the children showed much larger variability among subjects as compared to the adults. The children produced more than twice as large tracking errors suggesting less developed grip force control in dynamic isometric tasks. In both groups, no significant difference was found in force control between the dominant and nondominant hand [5]. In another study it was our aim to assess how the grip force control under visual feedback is affected in children with Down syndrome. The results showed that the healthy children were able to quickly understand the tracking task and performed all tasks with good accuracy. The children with Down syndrome required more time to adjust to the tasks [6]. The aim of the present study was to evaluate the differences in control abilities of power and precision grasping in three different age groups, 6-year, 9-year and 14-year old children. II. METHODS AND MEASUREMENTS Tracking tasks were applied when assessing the grasping abilities in three groups of children. Tracking tasks are visually guided motor tasks which require a person to track the presented target by application of the grasping force. The force output was presented on a computer screen simultaneously with the target. The tracking task was focused on both, spatial accuracy, where the accuracy in the position relatively to the target was emphasized, and on temporal accuracy, where the rate of tracking was important. Dynamic targets were moving according to randomized sinus, ramp, and rectangular signals. The selection of the target signal depends on the purpose of the assessment. The sinu-

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soidal targets are aimed to assess accuracy of tracking and endurance. The ramp targets are used to evaluate motor activity with a constant output rate and also muscle fatigue. The rectangular targets are aimed to assess performance of predictive behavior and temporal parameters of the sensorymotor system (e.g. response time). The accuracy of tracking was assessed by the root mean square error (rrmse) between the target and the measured response. Figure 1 shows the basic scheme of the grip force tracking system used in our studies [7]. For the assessment of grip force control, the child was presented with a target signal and the measured response on a computer screen. The target signal was shown in blue color and the force response in red color. Vertical position of a blue ring, located in the center of the screen, corresponded to the current value of the target and the position of a red spot corresponded to the applied grip force in real-time. The red spot moved upwards when the force was applied and returned to its initial position when the grip was released. The aim of the tracking task was to track the target as accurately as possible by adapting the force on the grip measuring device. The complexity of the task was adjusted by selecting the shape of the target signal (e.g. ramp, sinusoidal, and rectangular shape), setting the level of the target force and changing the dynamic parameters (e.g. frequency, force-rate). The measuring system (Fig. 2) was based on a compact device, which was connected to a computer through standard parallel port. The system consists of two forcemeasuring units of different shapes (cylinder and thin plate) which are connected to a personal computer through an interface box. Each device consists of a single point load

Visual feedback information

cell (PW6KRC3 or PW2F-2, HBM GmbH, Darmstadt, Germany), which is mounted in a metal construction. The shape and the size of the measuring units are similar to the objects used in daily activities (e.g. cup and key). The cylindrical unit allows the assessment of power grasp forces up to 300 N with the accuracy of 0.02% over the entire measuring range. The second unit (precision grasp) is made up of two metal parts which shape into a thin plate at the front end, resembling a flat-shaped object (e.g. a key). The load cell used can measure forces up to 360 N with the accuracy of 0.1%. The electronic circuit of the interface box consists of an amplifier with supply voltage stabilizer and an integrated 12-bit A/D converter (MAX197, Maxim Integrated Products, Inc., Sunnyvale, CA, USA) capable of sending data to the parallel port of a personal computer. The maximal supported sampling frequency of the force measurement is 1 kHz. The grip force control was evaluated while tracking three different targets: ramp, rectangular, and sinusoidal target. The amplitude of the rectangular and ramp signal was changing randomly during the test. When applying the sinusoidal target, the frequency was randomly increasing with time. During the test the subject was seated in front of the computer screen on a chair with adjustable height. The gripmeasuring device was positioned at the edge of the table in the proximity of the subject's hand. The peak forces of the target signals were set at about 10% of the average maximal grip force. The duration of each tracking task was 60 seconds. The preliminary study was performed in three groups of randomly selected children of both sexes. In the first group there were five 6-year old children, while in the second and third group the age was 9 and 14 years respectively.

Target signal Response

Target

Response

Computer

Subject

Force Measurement

Analysis

Fig. 1 Grip force tracking system used for the assessment of grip force control

Fig. 2 Power and precision grip measuring

environment

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III. RESULTS Figure 3 shows the average tracking errors and appertaining standard deviations while assessing cylindrical power grasp in three age groups. The tracking error was normalized by the peak value of the target. The results show that the oldest children performed the task with the lowest deviations. The largest tracking errors were found in the group of 6-year old children. The largest tracking error suggests that in group of 6-year old children the grip force control in dynamic tasks is not yet fully developed. Somewhat lesser differences among the age groups, as obtained when using the randomized rectangular signal, show that temporal accuracy is developed earlier than spatial accuracy.

Fig. 4 The average rrmse as obtained while assessing precision grip in three age groups of children during sinusoidal (above), ramp (middle), and rectangular (below) target signal. Similar results were obtained when studying the precision grip. Larger average tracking errors were found in 6year old children during precision as compared to power grasping, suggesting that precision grasps may develop later with age. IV. CONCLUSION

Fig. 3 The average rrmse as obtained while assessing power grip in three age groups of children during sinusoidal (above), ramp (middle), and rectangular (below) target signal.

In the paper we have presented a novel tracking method for evaluation of grasping using biofeedback on the grip force. Simple computer assisted tests using biofeedback can provide quantitative and reproducible measurements of physical activity which reflect subject's sensory-motor per-

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formance. The main focus of this work has been on the assessment of grip force control and its coordination in three different age groups of children. The results of the assessment in healthy children showed considerable differences in the grip force control among the three age groups. The results clearly demonstrate that the grip force control as well as the overall sensory motor functions are improved with age. Noticeable difference in performance between the precision and power grip was found only in 6-year old children. Future study should compare grip force control in still younger children to further investigate the changes of the motor control with age and to evaluate the sensitivity of the tracking method for possible use of the system for the assessment in young children with sensory-motor impairments.

REFERENCES 1. 2. 3. 4.

5.

6. ACKNOWLEDGMENT

The authors are grateful to Laboratory of Biomedical Engineering and Robotics at Faculty of Electrical Engineering, University of Ljubljana for lending the grip measuring device.

7.

MacKenzie CL, Iberall T (1994) Advances in Psychology, 104: The grasping hand, Elsevier Science B.V., Amsterdam Kurillo G, Bajd T, Munih M (2007) Assessment and rehabilitation of hand function by the grip force tracking method, in New Research on Biofeedback, Ed.: HL Puckhaber, Nova Science Publishers Forssberg H, Eliasson AC, Kinoshita H, Johansson RS, Westling G (1991) Development of human precision grip I: Basic coordination of force, Exp Brain Res, 85: 451-457 Gordon AM, Forssberg H, Johansson RS, Eliasson AC, Westling G (1992) Development of human precision grip III: Integration of visual size cues during the programming of isometric forces, Exp Brain Res, 90: 399-403 Kurillo G, Bajd B, Pikl V (2004) Grip force control of lateral grip in 10-year old children and adults, Medicon and health telematics 2004 : health in the information society : proceedings of the International Federation for Medical and Biological Engineering, (IFMBE proceedings, vol. 6), Ischia, Italy Bajd B, Kurillo G (2006) Assessment of grip force control in healthy children and children with Down syndrome, World Congress on Medical Physics and Biomedical Engineering, Imaging the future medicine, (IFMBE proceedings, vol. 14), Seoul, Korea Kurillo G, Gregorič M, Goljar N, Bajd T (2005) Grip force tracking system for assessment and rehabilitation of hand function, Technology and Health Care, 13: 137-149

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Development of a calibration bath for clinical thermometers I. Pusnik, J. Bojkovski and J. Drnovsek University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Metrology and Quality, Ljubljana, Slovenia

Resistance bridge with scanner Furnace with a fixed point

I. INTRODUCTION In the recent years infrared ear thermometers (IRETs) became very popular in clinical practice for measuring the temperature of a human body. Furthermore, many different thermometer models were introduced and became commercially available to common users. All IRETs are advertised and specified by manufacturers as being accurate and reliable measuring devices. In order to be able to verify their performance, an appropriate calibration set-up is essential, which in principle consists of a blackbody radiator (BBR) with a reference thermometer. Several standards were issued underlying this requirement that specify the configuration to be used. All standards mention the use of an appropriate BBR based on a specially designed cavity immersed in a temperature regulated stirred-liquid bath. For calibration of IRETs and clinical contact thermometers an accuracy of 0,2 °C is required in the range of 35,5 °C to 42 °C, setting requirements for employed BBRs or calibration bath better than 0,1 °C. The IRETs shall be accurate within ±0,2 °C in their operating range from 35,5 °C to 42 °C, or within ±0,3 °C outside the given range. The respective requirement in the ASTM standard is valid below 36 °C and above 39 °C. Experts in radiation thermometry can help manufacturers and medical staff in checking of IRETs’ compliance with the requirements of related standards. The experts can also provide the most important service for appropriate daily use and that is traceability. Without traceability to national standards it is impossible to estimate the level of quality of measurements

Maximum permissible error (MPE)

“True” value or Conventional true value

Traceability chain

Keywords— clinical thermometer, calibration bath, accuracy, uncertainty

with IRETs. Although metrologists are familiar with the terms in metrology, many times other people involved in measurements are confused with the meaning and use of some terms. To explain the terms in metrology, we should use the vocabulary of metrology terms. For easier understanding some terms in metrology are presented in Figure 1.

Dissemination of units

Abstract— In Europe the Clinical Device Directive (Council directive 93/42/EEC of 14 June 1993 concerning clinical devices) requires conformity of actual characteristics of clinical devices with manufacturers' specifications. Therefore we developed a water bath for simultaneous calibration of clinical non-contact (tympanic, ear, forehead) and contact (liquid-inglass, digital) thermometers by comparison with a traceable reference thermometer. The bath is intended for use in hospitals, health and veterinary institutes or calibration laboratories. The developed bath fulfills also the requirements of other world standards and future ISO standard on general requirements for clinical non-contact and contact thermometers.

22.821 °C

Digital Reference thermometer resistor in an oil bath

Primary level realisation of units (Metrological laboratories of national institutes)

Secondary level dissemination of units (accredited calibration laboratories)

Average value Correction Uncertainty

Uncertainty

Third level dissemination of units (internal calibration laboratories, e.g. in hospitals)

Measured values Measurement error Systematic error

User level of instruments (e.g. doctors, patients)

Maximum permissible (measurement) error

Measured value Random error

Fig. 1 Presentation of metrological terms II. DEVELOPMENT OF THE BATH A. Prototype To compare metrological characteristics of the proposed blackbody shapes, we developed a specially designed prototype of a stirred-water bath, in which cavities of different shapes were mounted. The bath was evaluated in terms of temperature stability and homogeneity in the range from 35 °C to 42 °C. The dimensions and emissivity of the cavities were measured and calculated. With the developed calibration bath we were able to perform such calibration of an IRET, in which the uncertainty of a calibrated IRET is a prevailing contribution to the total uncertainty budget. The prototype bath was made of stainless steel and had a shape of an octagonal prism. The water level was at least 15 cm above the cavities, total of approximately 90 liters. The flow of water was regulated with the help of a cylinder placed around the motor shaft with the propeller. It forced water to circulate through the cylinder downwards and through the specially designed plates with manually adjustable openings up again, Figure 2. One plate was positioned 5 cm above the bottom of the bath. Another plate was positioned 5 cm below the surface of the water. The openings in

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 338–341, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

339

φ =38,6°

2,122

2,078

115,331

φ =36,1° 108,631

39,630

both plates were placed in three concentric circles. With appropriate adjustment of the openings we had achieved the stability of 2 mK/hour (2s) and the homogeneity of 18 mK (2s) inside the whole bath and in the worst case, which was at 42 °C. For the purpose of the bath evaluation eight small sealed platinum resistant thermometers were manufactured. They were calibrated by comparison in our laboratory with the uncertainty of 4 mK in the range from 0 °C to 50 °C. The thermometers were connected to the ASL F700B a.c. resistance bridge and arranged at different extreme positions inside the bath. To exclude the influence of uncertainty of thermometers their positions were exchanged several times. Also between the measurements their short-term stability was regularly checked in the ice point.

32,931

Development of a calibration bath for clinical thermometers

99,090 26,977

198,194

9,012

8,903

63,052

51,188

φ =120,0°

41,4 59

64,745

58,045

α =40,8°

1,955

2,018

54,068

8,857

196,537

9,125

Fig. 3 Shapes of the blackbody cavities a) EN, b) ASTM, c) JIS, d) LMK at the temperature 50 °C, Figure 4. Measurements of emissivity were performed on a copper disc, which was made and painted in the same way as the cavities. In addition also the surface treatment, painting and drying procedures were identical. 1

0,98 '50°C, angle 90°' '36°C, angle 90°

0,96

'50°C, angle 60° 0,94

'50°C, angle 45°

Emissivity

0,92

0,9

0,88

0,86

0,84

Fig. 2 Plates with manually adjustable openings for regulation of water flow and arrangement of the cavities in the prototype bath

0,82

0,8 8

9

10

11

12

13

14

15

16

Wavelength in micrometers

B. Blackbody cavities Inside the prototype bath different blackbody shapes (Figure 3) were mounted according to the suggested shapes in the following documents: - European standard EN 12470-5, [1], - standard ASTM, Designation E 1965 – 98, [2], - Japanese Industrial Standard JIS, Infrared ear thermometers - draft standard, [3]. - LMK design (elliptical shape) The cavity wall material was identical for all cavities, that was copper, coated with three layers of a highemissivity black paint (Pyromark 800). We performed the measurement of emissivity with a FTIR spectrometer [4], corresponding to the spectral range from 8 μm to 16 μm and

Fig. 4 Results of emissivity measurement The emissivity of each cavity was modeled based on its configuration, measured emissivity of the copper disc and temperature conditions in the bath. The effective emissivity was calculated by the software program STEEP, which was used in the TRIRAT project [5]. In Table 1 the results of the temperature stability and homogeneity, and of the calculated directional emissivity for all cavities under investigation are presented. It was taken into account that the opening angle of a reference IRET was 7 degrees, and the front of it was placed at the aperture of a blackbody cavity. It was assumed that in the worst case the field of view was twice as large, therefore the directional emissivity was calculated at the angle of 14 degrees. The emissivity value was stated as the worst case, taking into account the temperature gradients. The uncertainty of emissivity was considered as the rectan-

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gular distribution, where the emissivity of an isothermal cavity, temperature gradients at high temperatures (42 °C) and temperature gradients at low temperature (35 °C) were taken into account. The emissivity value for the EN shape of cavity was not calculated because it was not symmetrical around the horizontal axis. The value of its emissivity and the associated uncertainty was estimated as the value between the values of ASTM or JIS shape (higher emissivity values) and the value of LMK shape (lower emissivity value). The blackbody radiator with different cavities was compared together with a reference IRET with another blackbody and a reference IRET of the National Physical Laboratory of UK. Results of comparison were presented in detail in [6]. Table 1

Temperature stability, temperature homogeneity, and effective emissivity of ASTM, EN, JIS and LMK cavity

Type of theTemperature Temperature Emissivity (50 °C; blackbody stability at 42homogeneity at 8 μm - 14 μm), angle 14° cavity °C 42 °C

ASTM EN* JIS LMK

2 mK (2s) 8 mK (2s) 1,4 mK (2s) 6 mK (2s) 2 mK (2s) 17 mK (2s) 1,2 mK (2s) 6 mK (2s)

0,99980±0,00003 0,998±0,001*(estimated) 0,99974±0,00005 0,99734±0,00002

C. Bath for calibration of clinical non-contact and contact thermometers Following the results obtained with the prototype bath we developed a smaller portable stirred-liquid bath with approximate volume of 15 liters. The bath has a special

design with two tubes to achieve a laminar flow and hence a very high temperature stability and homogeneity, both better than ±0,02 °C. In the main tube an equalizing block for calibration of contact and a copper blackbody for calibration of non-contact thermometers are mounted. The shape of a blackbody cavity may be chosen by a customer among the suggested standard shapes. For the developed bath a patent application was filed. The bath is presented in Figure 5. III. CONCLUSIONS Based on several experiments, of which some results were presented in [7], the answer to the question, what do most commonly used IRETs measure, and whether they meet the requirements of the standards, cannot be given only by relying on manufacturers’ specifications. Therefore the compliance with the standards can and has to be verified, either by manufacturers or other relevant institutions, which are competent for radiation thermometric calibrations, and are traceable to a national measurement standard. Traceability must be assured via the BBR, which is evaluated in terms of emissivity and temperature homogeneity as well as stability. It is not appropriate to use quasi-calibrators with undetermined emissivity and temperature characteristics. Less problematic is calibration of clinical contact thermometers. Using the developed calibration bath all requirements in different standards related to calibration of non-contact and contact thermometers can be fulfilled at the same time.

ACKNOWLEDGMENT The authors wish to express their sincere thanks for support in development of the prototype and the calibration bath to the managing director Mr. Anton Kambic and the technical director Mr. Gorazd Kambic of the company Kambic Laboratorijska oprema. The development of the bath was partially supported by the European Fifth Framework Programme project INCOLAB under the specific programme “Promoting competitive and sustainable growth”, generic activity “Measurement and testing” and by the Ministry of Economics of the Republic of Slovenia.

REFERENCES 1.

Fig. 5 Developed bath for calibration of clinical non-contact and contact thermometers

EN 12470-5, Clinical thermometers – Part 5: Performance of infra-red ear thermometers (with maximum device), 2003, CEN, Brussels

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Development of a calibration bath for clinical thermometers 2.

3. 4.

5.

ASTM, Designation E 1965 – 98: Standard Specification for Infrared Thermometers for Intermittent Determination of Patient Temperature, Annual book of ASTM Standards 1998, West Conshohocken, PA 19428, USA Draft of JIS, Infrared ear thermometer, Japan Measuring Instruments Federation, 2001 Clausen S., Measurement of spectral emissivity by a FTIR spectrometer. Proceedings 8th International symposium on temperature and thermal measurements in industry and science (TEMPMEKO 2001), Berlin (DE), 19-21 June 2001, Vol. 1., pp. 259-264 Bosma R., van der Ham E. W. M., Schrama C. A., Test results on workpackage 5, 6 and 7 for the project TRaceability In RAdiation Thermometry (TRIRAT)– NMi/VSL contribution, February 1999, NMi/VSL, Delft, The Netherlands

341 6.

7.

Pusnik I., Simpson R., Drnovsek J., Bilateral comparison of blackbody cavities for calibration of infra-red ear thermometers between NPL and FE/LMK, IOP Physiol. Meas. 25 (2004) pp. 1239–1247 Pusnik I., E. van der Ham, Drnovsek J., IR ear thermometers what do they measure and how they comply with the EU technical regulation, IOP Physiol. Meas. 25 (2004) 699– 708IFMBE at http://www.ifmbe.org Address of the corresponding author: Author: Igor Pusnik Institute: University of Ljubljana, Faculty of Electrical Engineering. Laboratory of Metrology and Quality Street: Trzaska 25 City: SI-1000 Ljubljana Country: Slovenia Email: [email protected] lj.si

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Development of Implantable SAW Probe for Epilepsy Prediction N. Gopalsami1, I. Osorio2, S. Kulikov3, S. Buyko3, A. Martynov3 and A.C. Raptis1 1

2

Argonne National Laboratory, Argonne, IL Flint Hills Scientific, Lawrence, KS and University of Kansas Medical Center, Kansas City, KS 3 Biofil Ltd., Sarov, Russia

Abstract— An implantable surface acoustic wave (SAW) microsensor has been developed for early detection and monitoring of seizures based on local temperature changes in the brain’s epileptogenic zones that occur prior to and during an epileptic event. Three SAW sensors were designed and fabricated: a 172 MHz filter, a 434 MHz filter, and a 434 MHz delay line. Their temperature sensitivities were tested by measuring the phase change between the input and output waveforms as a function of temperature. We achieved a phase sensitivity of 144 phase degrees per оC and a minimum detectable temperature of 5 mK for the 434-MHz, 10.2-µs delay line. Based on the sensitivity tests, a prototype 434 MHz SAW sensor was fabricated to a size of 11 x 1 x 1.1 mm, which is commensurate with existing brain implantable probes. Because of possible damping of the surface waves by the surrounding tissue or fluid, a glass housing with dry air was built on the top of the SAW substrate. Test and reference sensors were used in the prototype system to minimize the effect of source instabilities and to amplify the temperature effect. The phase change between the output waveforms of the sensors was measured with phase detector electronics after they were converted to lower (10.7 MHz) frequencies by standard mixers. The complete prototype sensor was tested in a saline water bath and found to detect as low as 3 mK changes of temperature caused by the addition of hot water. Operation ability of the system in its wireless variant was demonstrated. Keywords— Implantable, SAW, epilepsy, temperature sensor.

I. INTRODUCTION Epilepsy is a neurological disorder that affects at least 2.7 million Americans of all ages. This figure amounts to about 1% of all Americans, which is equivalent to that for all industrialized countries. The percentage presumably rises to as high as 10% for underdeveloped countries [1]. The fact that up to 40,000 Americans die each year directly from seizures in a country where medical care is the most advanced in the world underscores the malignancy of this disease. Most people with epilepsy, although of normal intelligence, are either unemployed or sub-employed due primarily to the unpredictability of seizures. Despite current advances in drug therapy, only 15% of those treated have neither seizures nor side effects. The negative impact of

epilepsy on the lives of those who suffer from it and on their families and communities can be considerably lessened if a means for early detection of seizures is found and innovative therapies, such as non-pharmacological treatments, are developed. Early detection of the onset of seizures is critical for implementing appropriate prevention measures, such as electrical stimulation, cryogenic cooling or drug delivery [2]. Although monitoring the electrical potentials with electrodes implanted in the brain is commonly used for the detection and prediction of seizures, changes in temperature associated with epileptic neuronal activity could provide additional relevant information. In addition, the neuronal activity could be tracked while electrical stimulation is being delivered to the area generating the activity of interest. Neuronal activity, particularly if intense, as in epilepsy causes local temperature changes in the brain tissue. Cortical temperature variations on the order of ±0.2 oC have been observed in animal tests with visual and other forms of stimulation [3]. Sensing local changes in the brain temperature associated with neuronal disorders requires accurate and implantable microsensors that can operate in the brain cortical zones for long periods of time and ideally can work without a power source. Furthermore, a microsensor implant must be compact (1000) using low noise amplifier and filtered to remove noise. Filters are used to remove the 50Hz hum and suppress the T-wave of the ECG signal (not required to detect the heart rate) to help keep a steady DC point. The use of an op-amp appeals in this situation. However further consideration reveals it is not so suitable. The previously alluded to noise would saturate the op-amp upon amplification, and the signal would be lost. The medical industry uses “instrumentation amplifier” in situations like these. Instrumentation amplifiers have the property of passing common mode signals (like 50Hz noise from electricity) as a small percentage of the differential of the signal. The common-mode rejection ratio (CMRR) is the ratio of amplification of the signal divided by amplification of the common mode input. A high commonmode value is recommended in this application. A standard single supply instrumental amplifier is used for the differential bioelectrical amplifier in the ECG-sensor. The differential amplifier can be used is Burr Brown INA118 [7]. The INA114 is a low cost, general purpose instrumentation amplifier offering excellent accuracy. Its versatile 3-op amp design and small size make it ideal for a wide range of applications. It is very suitable for this application with a large common mode rejection ratio, approximately 120dB, and low supply voltage, 1.35V. This particular amplifier has a CMRR of 115dB, which is considered high and meets the American Advancement of Medical Instrumentation’s (AAMI) specification on electrocardiography. DC wander: Electrodes placed against the skin cause a varying DC offset known as DC wander [8]. To help remove this DC wander, an integrator can be added to the circuit. The integrator takes its input from the output of the differential amplifier and its output is attached to the reference pin of the same amplifier. This provides a changing DC bias for the first amplifier stage which depends on the output of the same stage. This greatly

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Hardware optimization of a Real-Time Telediagnosis System

reduces the DC wander seen at the output of the differential amplifier which means that the gain of the second stage can be maximized without having to worry about saturation due to DC wander. Right Leg Drive (RLD): The function of the Right Leg Drive (RLD) is to eliminate the common mode noise generated from the body. The two signals that are entering the differential amplifier from the leads placed on the right and left arm according to Einthovens triangle [9] are summed, inverted and amplified back into the body through the right leg by a common-mode amplifier. This signal is fed back to the other leads and eliminates the noise signal drowning the wanted ECG signals [10]. Voltage gain and Filter: To remove the unwanted frequencies in this case requires three filters. ƒ A low-pass filter is implemented to remove baseline wander of a patient. ƒ A notch or band-reject filter is used to reduce 50Hz noise. ƒ Finally, a high-pass filter is used to remove frequencies higher than 100Hz. It would not be wise to use a band-pass filter in this case as the pass-band is large, and after the consideration of three options, cascaded high-pass low-pass filters is recommended [11]. After the unwanted frequencies are filtered out, the gain can be added. From calibration and simulation it is deemed that this amplification should occur by a factor of around seven or eight. The signal is amplified and inverted by an op-amp, using the inverting input as its signal path. This is done because the next stage, the summing amplifier, can only be implemented on the inverting input, and will invert the signal.

407

in the positive domain is to add one or two 1.5VAA batteries with the positive terminals attached to ground. The operational amplifiers recommended for the filter, right leg driver, integrator and second amplification stage are National Semiconductor LMV771 and LMV774. These are the single amplifier and quad pack respectively. These are suggested because of the low supply voltage 2.7V and small supply current 550MA. D. Microcontroller Advanced microprocessor devices for the telediagnosis unit: A real-time telediagnosis system needs to be portable, small in size, inexpensive and feature-extendable. So it should be implemented in a one-chip microcontroller that integrates: an analog to digital converter (ADC); digital signal processing and temporal storage in working memory (RAM), and a digital interface to the transceiver device. In the following table we made a comparison between four microcontrollers which we found prospective and suitable for developing the telediagnosis system: AT90LS8535, ATMega128L (produced by Atmel), PIC16F8X (by Microchip), and MSP430F149 (by Texas Instruments). Some of the key characteristics which are important for choosing the most appropriate solution are: (a) physical dimensions; (b) active power; (c) number of ADC; (d) RAM. We may need to convert multiple analogical signals in case of the diagnosis of other biosignals along with the ECG and probably to compress the digital signal. Hence, in order to maximize the number of channels transmitted and reduce the energy needed for transmission, we need more ADCs and RAM. One could also use analogue multiplexers, at the cost of increased total physical dimension of the system. It is also possible to use implanted amplifiers and multiplexers [12], but this is a matter of further research and commercial availability.

Vendor

Finally the signal must be brought into the range of zero to five volts to enable the analog to digital converter to perform analysis on it. It is seen that the output voltage is the sum of the negative amplification of the input voltages. Here the gain is one, as all resistors are set to the same value, so the output is the addition of the signal and offset voltage inverted. In practice, the signal is around four volts peak-to-peak, so the best way to make the signal reside only

Bits Flash (bytes) RAM (bytes) ADC Timer Voltage Active Power Idle Power

AT90 LS8535 Atmel

ATMega128 MSP L 430F149 Atmel Microchip

8 8K

8 128K

16 60K

Texas Instruments 8 68K

512

4K

2K

1K

8 x 10bit 3 4-6V 6.4mA

8 x 10bit 3 2.7-5.5V 5.5mA (4MHz) 2.5mA (4MHz)

4 x 12bit 3 1.8-3.6V 400μA

1 2-6V 2mA

1.9mA

PIC16F8X

1.3μA

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Muhammad Kamrul Hasan, Md. Nazmus Sayadat and Md. Atiqur Rahman Sarker

Choice of a microcontroller: Analyzing the characteristics of the microcontrollers (MCUs) shown above, we can conclude that ATmega128L is most suitable for the telediagnosis system. This MCU is chosen because: ƒ It is low cost, has a small footprint and most importantly, it has all the peripherals required built-in. ƒ It is an 8-bit MCU clocked at up to 8MHz. When clocked at 4 MHz, it consumes only 5.5mA in active mode. ƒ It has 128 Kb of FLASH memory (reprogrammable more than 10000 times), 4 Kb of EEPROM and 4 Kb of SRAM. Data could be temporally stored on the 4 KB onchip memory, but an external memory of 64 KB could also be added. Control software and supporting data could be stored in the on-board 128 KB flash-memory. ƒ This MCU has 8 analog input ports on the board, which allows sampling from 8 micro-sensors without external ADC. The ADC subsystem is extendable to 32 channels using a multiplexer. The analog inputs could be measured with a total frequency of up to 500 KS/s with a resolution of 8 bits per channels. ƒ There are 2 UARTs onboard; one for digital communication with the external Bluetooth module and another for debugging. ƒ It features a low voltage power supply detector which we can use for monitoring the state of the battery [13]. E. Communication Protocol In the race of eliminating any form of wiring between products by adopting wireless RF (Radio Frequency) based technologies, the designers are faced with an ever growing number of communications protocols. As communication is a vital part in the development of a real-time telemonitoring device, the design decision regarding the communication technology has far reaching implications on scenarios and applications that can be supported and built based on this device. Nowadays there are various wireless RF communications technologies– a breadth of choice that makes difficult identifying the optimum technology for a given application. Short-Range Wireless (SRW) networks such as Blue tooth, ZigBee, RFID and IR, are gradually becoming more and more widespread in modern information systems. Most of these SRW networks have some drawbacks as the transmitting distance is less or else they are prone to disturbance due to outside environment. To keep the system power consumption low and to increase security, an own system of short range communication can be developed. But as said earlier the problem in this case is, the mobile phone or the PDA has to be equipped with the same transceiver. So it is better to go

for a protocol for which we don’t have to make any change in the devices like PDA or mobile phone. Again the IrDA technology needs direct visibility [14] between the two nodes and has bandwidth and energy consumption less advantageous than Bluetooth or ZigBee. From the above analysis we can consider that Bluetooth and ZigBee are most relevant for the specific requirements of a telediagnosis system: large transmission data-rate and low energy consumption. Bandwidth Energy Consumption(mw) Range(m)

IrDA 9.6-115 10

Bluetooth 720 150

ZigBee 20-250 1-2

5

10

100

ZigBee is advantageous as a communication protocol due to two main reasons: (i) Low energy consumption and battery life, (ii) Wider range but it has a relatively limited bandwidth (20 / 250 kbps) [15]. In contrast, Bluetooth has the following points for being candidate communication technology for the Real-Time Telediagnosis System: ƒ As the number of consumer devices such as PDAs, Laptops, cellular phones that are equipped with Bluetooth modules increase rapidly; Bluetooth provides a degree of interoperability to easily integrate augmented objects into existing computing environments. ƒ Bluetooth targets low-cost, low-power, secure and robust short-range connectivity. The technology has been designed for ease of use, simultaneous voice and data, and multi-point communications [16]. ƒ Studies indicate that blue tooth technology is electro magnetically compatible with the tested medical devices [17]. ƒ The bandwidth of Bluetooth (720 kbps) is about three times as much as that of ZigBee. This is achieved, however, at the cost of increased energy consumption: a Bluetooth-based system is expected to have autonomy of up to several days. If we use rechargeable battery in the sensor-end then it can be charged by the user everyday or every alternative day. In this application it is acceptable to trade bandwidth to save energy. Again, a lower bandwidth generally results in longer communication times (longer on-times) that could counter the saving effect. Therefore, in the design the optimum of bandwidth vs. energy consumption should be assured. As in our system we want the ECG graphs to be transmitted to a distant client if requested and we want our system to have the option of appending multiple sensors for monitoring

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and analyzing various biosignal of the body, we need a wide bandwidth for transferring our data. ƒ Compared to communication protocols specifically designed for the telemonitoring sensor networks, communication via Bluetooth consumes significantly more energy. However, in applications where the communication modules can be switched off most of the time and the need for communication be recognized by considering local sensor readings only, the Bluetoothbased Telemonitoring System is well suited for realizing typical Portable wireless real-time telediagnosis scenario. ƒ Bluetooth networks have a more limited range than ZigBee networks (10m. vs. 100m). However, the person with the Telediagnosis system will carry the mobile phone with him which is within the range of the basic low-consumption Bluetooth devices. Finally we can conclude that in applications where interoperability is paramount and access to commercial user devices is required a Bluetooth based solution is most preferable. So in the Real-time Telediagnosis System we suggest Bluetooth as the perfect communication protocol. As far as the Bluetooth communication is concerned, it could be implemented with the one-chip solution by Ericsson: ROK 101 008 a short-range module that implements full Bluetooth functionality. It operates at 5 V and consumes 26 mA during data-transfer mode. It is 3.2x1, 6x0.275 cm. large and weights less than 3 gr [18]. III.CONCLUSIONS This article presents our preliminary investigation for the realization of a real-time telediagnosis module. Throughout our study our main aim was to make the system more robust and reliable not increasing its weight, size and cost. For this reason we have developed the system on the basis of various integrated circuital modules. The next stage of the research will focus on the implementation of sensor node and network coordinator software in the TinyOS environment. The aim will be to develop and implement a telediagnosis system which will satisfy requirements for minimal weight, miniature form-factor, low power consumption to permit prolonged ubiquitous monitoring; seamless integration, standards based interface protocols, short development cycle and patient-specific calibration, tuning, and customization.

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REFERENCES 1.

A. Karilainen, S. Hansen, and J. Müller, “Dry and Capacitive Electrodes for Long-Term ECG-Monitoring”, 8th Annual Workshop on Semiconductor Advances, 17 Nov 2005, pp 156.

2.

G. M. Friesen, T. C. Jannett, M. A. Jadallah, S. L. Yates, S. R. Quint, and H. T. Nagle. “A comparison of the noise sensitivity of nine QRS detection algorithms,” IEEE Trans. on Biomedical Engineering, vol. 37, no. 1, Jan. 1990. Engelse W. A., and Zeelenberg C., “A single scan algorithm for QRSdetection and feature extraction”, IEEE Computer Cardiology: IEEE Computer Society, 1979, 37-42. J.P. Baker, Assoc. Prof. P.J. Bones, Dr. M.A. Lim, “Wireless Health Monitor,” Electronics New Zealand Conference 2006 Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, “Heart Rate variability standards of measurement, physiological interpretation, and clinical use”, European Heart Journal, vol. 17, Mar. 1996. INA114 BURR-BROWN Precision Instrumentation Amplifier specification. Available: http://www.ti.com/productcontent/ina114.html P. Laguna, R. Jane, and P. Caminal, “Adaptive Filtering of ECG Baseline Wander,” Engineering in Medicine and Biology Society, Vol. 2, pp 508-509, 1992 http://www.cvphysiology.com/Arrhythmias/A013a.htm E.M. Spinelli, R Pallas-Areny, and M.A. Mayosky, “AC-Coupled Front-End for Biopotential Measurements,” IEEE Transactions on Biomedical Engineering, Vol. 50, no. 3, pp 391-395, 2003 Kerry Lacanette, A Basic Introduction to Filters – Active, Passive, and Switched-Capacitor, National Semiconductor Application note 779, April 1991. Jan Beutel, Oliver Kasten, “A Minimal Bluetooth-Based Computing and Communication Platform,” IT Papers, June 2001, Available: http://www.itpapers.com/abstract.aspx?compid=16237&docid=91473 Atmel Corporation, ATmega128(L) - Datasheet Complete, 11/2004, Available: http://atmel.com/dyn/general/tech_doc.asp?doc_id=7236 Eric Glaenzer, SIG WirelessOne, PAN - Personal Area Network, (2004) www.siliconfrench.com/workshops/ presentations/PanSiliconFrench.ppt ZigBee Alliance, Available: http://www.zigbee.org/ Atmel Corporation, Blootooth General Information. Available: http://www.atmel.com/dyn/products/product_card.asp?part_id=2205, 2000 Mats K. E. B. Walling MD, MSc t, and Samson Wajntraub, MSc t, “Evaluation of Bluetooth as a Replacement for Cables in Intensive Care and Surgery,” Critical Care and Trauma, Technical Communication, September 8, 2003. Ericsson Microelectronics AB, Ericsson Bluetooth module: ROK 101 008, Datasheet, 2000, pp.1 – 12

3. 4. 5.

6. 7.

8. 9. 10. 11. 12. 13. 14. 15.

16.

Author: Muhammad Kamrul Hasan Institute: Street: City: Country: Email:

Bangladesh University of Engineering and Technology 406, Sher-e-Bangla Hall, BUET Dhaka Bangladesh [email protected]

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Home Care Technologies for Ambient Assisted Living Ratko Magjarevic University of Zagreb, Faculty of Electrical Engineering and Computing, Zagreb, Croatia Abstract— Health technology and increased medical knowledge enable accurate diagnostics and effective treatment of a large number of diseases, including those which only a decade ago were not easy to manage and cure. The interest and biomedical research in the modern society is intensively directed on disease prevention, early diagnostic and life quality improvement as well as on development of personalized healthcare especially for those chronically ill, disabled and for the aging population. The aim of the new approach in healthcare is not only to monitor and improve health of individuals, but also to increase their independence, mobility, safety and social contact through increased communication, inclusion and participation using available technologies. A large number of new medical devices for health monitoring, home care, wellness promotion, gerontotechnology, etc. have to be designed, tested and adopted to meet the special needs and demands of different population groups. These new devices for telemonitoring and telediagnostics create large amount of health related information, in most cases from sensors organized into body sensor networks. The information has to be processed, transmitted from the point of care to the healthcare system in a safe way and after managing the information in an appropriate and intelligent manner, decisions related to the persons health are to be made. This paper brings an overview of some solutions presented in literature as well as our own development of intelligent mobile monitoring devices. Keywords— Personalized healthcare, ambient assisted living, body area network, telemonitoring, telediagnostics

I. INTRODUCTION The average age of the population is increasing considerably, especially in the developed countries. In order to meet the rising demand for health care and other social services for the elderly, the policy makers have decided to encourage a number of research and development projects which combine enabling possibilities of communications, information technology, sensorics and health education. Due to ageing of population, the prevalence of chronic diseases has increased and at the same time the citizens have extended their demands for the best available health care. The life style, increased stress and workload tend to increase the disease risks in middle aged and younger population and therefore a need for developing disease prediction and early detection programs and devices has risen in order to increase the quality of life and reduce the costs by pro-

viding as many as possible services at citizens home [1, 2]. Both, patients and healthy, are prepared to carry different intelligent and networked sensors continuously in order to improve their health and well being. Such wearable devices must comply with many requirements, in addition to their medical functionality and technical specifications: they have to be easy to use, reconfigurable, interoperative [3]. Physiological parameters are measured and processed by body sensor networks often based on e-textiles [4, 5, 6], transmitted to the immediate surrounding such as wristwatch, PDA, or PC [7]. The information may be collected and processed in a medical institution, or at their home. In some cases telemonitoring is covered by global GPS or GIS [8]. The ambient has been adopted by embedding sensors into smart homes in order to provide health monitoring of individuals, and also to increase their independence, mobility, safety and social contact through increased communication, inclusion and participation using available technologies [5, 9, 10]. Smart homes require integration of a large number of sensors and device monitoring with a set of processing and decision making devices resulting with a large number of different applications [11]. The concept of ambient assisted living has been created within EU FP6 as a program for funding research and development with outcomes that enhance the life quality of the elderly and of the old primarily by using ICT innovations and by providing remote services. This program shall be continued until at least 2013. The citizens’ acceptability of e-Health services is rising worldwide and e.g. the expectations for the EU are that by 2010 up to 5% of the health budget will be spent on these services [12]. II. FROM HOME CARE TO PERSONALIZED HEALTH CARE Patients do not any longer receive care only in medical facilities. The health care services have spread first to their home and then also to other spaces they reach, and finally there is a tendency to offer the services universally. Also the number of users and potential users has increased since in addition to the need for monitoring either vital functions of patients or their general health status, the wish for continuous information on health status and potential health risks have developed in healthy population also. Health care technology research and development have followed these

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needs but there is still a need for further steps in order to cover all applications, from disease and health management, disease prevention and possibly prediction. These efforts are intended for a not static citizen, moving across the borders, at any time, but also under non uniform legal framework, unclear reimbursement policy and high requirements for reliability,security and privacy. A. Home care Medical devices and services for home care first developed out of the need to extend patient monitoring after medical interventions, using minimally or non-invasive methods allowing early patient release from the clinical facilities. Currently, the home care devices can be divided into several groups: • • •

Stationary medical devices used at home to measure particular physiological parameters, transmit them to the center of care within a regular schedule, Devices embedded into the home in order to raise alarm in case of a medical need or accident, Wearable sensors and sensor networks that continuously monitor several physiological parameters.

Stationary medical devices are used to measure physiological parameters which do not need to be monitored continuously or the measurement cannot be performed in such a way. A typical parameter in this category is blood pressure, still considered difficult to determine by users themselves. New developments resulted in a more suitable device for home use, which measures ECG and photolethysmographic (PPG) signal as well [13]. Other systems are based on personal computers as base stations for raw data acquisition where multiple parameters (e.g. HR, RR, ECG, SpO2) are collected and processed to produce decision supportive information, while the data is stored in the computer or transmitted to a medical center [14]. Health smart home (HSH) was designed to follow elderly and disabled people in order to avoid hospitalization. Several modalities of monitoring have been introduced: automatic measurements of physiological parameters, activity measurement and disease specific measurements, allowing monitoring of patient’s daily activity within his home [15]. However, the intention is to minimize the interventions in the infrastructure. Thus, the design of existing devices has to be added with medical functionality. Wireless LAN, environmental sensor network for temperature, humidity and carbon dioxide monitoring are interfaced to devices for physiological measurements [16]. Embedded devices certainly provide more comfort to users than wearable devices. Since development of the home care concept is related to care for elderly people, highly

accurate automatic fall detectors are important for their care. In addition to devices which require the user to wear and activate them, passive and unobtrusive devices based on floor vibration- detectors have been proposed [17]. Sensors are incorporated into furniture, e.g. into beds in order to follow parameters during sleep [18]. However, such build in devices can produce data on a very limited number of patient related information and therefore can be taken only as a part of intelligent environment. Wearable devices present the vast majority of devices used for home monitoring. However, there are several modalities of monitoring devices and concepts: •

•

•

•

Biotelemetry, as a classical form of data acquisition and transmission, where at the side of the moving transmitter (i.e. patient) only a limited number of parameters is measured and only limited processing is performed, usually in order to compress the data and reduce the power consumption necessary for raw data transmission [19]. Portable medical devices, personal medical assistants, intended for use at home to facilitate patient centered care and to enable communication with a medical center through wired services as a part of telematic network. Body area network (BAN), which enables wireless communication of a central data storage device with numerous sensors attached to the (patient’s) body. Miniature integrated circuits allow measurement and communication at ultra low power and low weight [17]. The aim of introducing these networks is extracting, intelligent processing and transmitting information to devices which communicate with national healthcare information systems. BANs have facilitated research of numerous new miniaturized sensors for physiological data measurement such as ear worn sensors [20] or different types of dry electrodes [21]. BANs should be designed so that they do not reduce the mobility of the persons wearing them. Intra-body communication networks or personal area networks have also been proposed for data communication between sensors within or in the near vicinity of the body surface [22].

B. System Integration Body area networks produce a large amount of data which has to be reliably transferred to the base station and/or server. The majority of signal processing is preferably performed within the wearable unit using embedded intelligence [23, 24, 25]. There are many technical constrains, e.g. limited band, power consumption, interference

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Fig. 2 Results of the wheeze detection in one of the recorded respiratory signals a) spectrogram with marked wheezes (w), b) extraction using connected components, c) detected wheezes in time

Fig. 1 Body area network for monitoring physiological parameters. Each intelligent sensor is comprised of an acquisition unit (Acq), processing unit (DSP) and a radio frequency transmitter (RF) connected wirelessly into a WBAN. Main unit communicates with the base station in an intelligent ambient.

between different networks – objects. Challenging issues that have also to be resolved are system configuration, customization and integration, standardization of communication protocols, use of off-the-shelf components, as well as security and privacy issues. Body area network for monitoring physiological parameters typically comprises of a number of intelligent sensors which in turn have an acquisition unit (Acq), processing unit (DSP) and a radio frequency transmitter (RF) in order to wirelessly connect all of them into a WBAN. Fig. 1 shows a system being developed at the University of Zagreb. The main unit processes information obtained from all sensors and communicates with the base station, positioned in this case in a smart home, either directly or through a network of simple auxiliary transceivers. A “traffic light” communication between the main unit and the ambient has three levels: a) alert, in case information processing showed unhealthy condition of a patient in need of immediate attention, b) warning, in case the processing showed suspicious information or trends and c) normal condition, when only short messages are exchanged in order to maintain the communication and acquire the position of the patient. The signal and information processing algorithms enable data compression suitable for communication. Fig. 2 presents how from complex signal processing i.e. from a spectrogram obtained from an asthmatic patient (a), the critical par-

ameter – wheezing is extracted (b) and reduced to a one dimensional information, i.e. presence of wheezing in continuously monitored patient record (c) [24]. The messages to the base station from the main mobile patient unit contain an identification part and a set of physiological parameters individually set for the needs of monitoring of each patient. E-textiles enable structures which integrate electronic components with textiles, while the term i-textiles designates interactive structure beyond just passive incorporation of electronics and textiles [6]. Smart shirts, also called “wearable motherboards” form wearable infrastructure consisting of a number of sensors integrated into a textile which is as comfortable as traditional clothes [4]. Cellular phones are often used as a platform for communication with the base station. Physiological data is processed and summarized to enable transmission to a remote server in regular time intervals by SMS [26] or the system is configured as an alert system targeting alert message receiving from highrisk patients. The alert system includes continuous collection and evaluation of multiple vital signs and detection of emergency [27]. C. Personalised Care Innovative systems based on wearable and portable systems will soon include personalized health status monitoring, enabling early diagnosis of disease based on monitoring and analysis of physiological parameters and guidelines for appropriate treatment. The alerting systems will incorporate new algorithms for prediction, detection of symptoms and extraction of adverse events [28, 29, 30]. The knowledge will incorporate results of data mining of existing medical

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and scientific databases and blind separation methods for handling large amounts of clinical data. Our environment will become, consciously or unconsciously, a part of ambient assisted living enabling predictive, personalized health care based on patient-specific modelling and simulation. III. DISCUSSION AND CONCLUSIONS Health monitoring will in future include monitoring of patients and healthy persons and it will consist dominantly of body sensor networks, either implanted or surface sensors and a personalized, powerful computational unit with embedded intelligence, designed to recognize changes in person’s health and context. This personalized unit will enable ubiquitous presence within the health care system. Accordingly, it will be reconfigurable, it will communicate with the ambient to assist changes in regard to living conditions and also activate devices e.g. within rehabilitation program or for drug delivery.

ACKNOWLEDGMENT This study was supported by Ministry of Science, Education and Sport of the Republic of Croatia under grant no. 0361554.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Scanaill C et al., (2006) A Review of Approaches to Mobility Telemonitoring of the Elderly in Their Living Environment. Ann. Biomed. Eng. 34: 547-563 Kochm, S (2005) Home telehealth – Current state and future trends. Int. J. Med. Info. 75:565–576 Paradiso R et al., (2005) A wearable point-of-care system for home use that incorporates plug-and-play and wireless standards. IEEE Trans. Inform. Technol. Biomed. 9: 337-344 Boger J et al., (2006) A Planning System Based on Markov Decision Processes to Guide People with Dementia through Activities of Daily Living. IEEE Trans. Inform. Technol. Biomed. 10: 323-333 Axisa F et al., (2005) Flexible technologies and smart clothing for citizen medicine, home healthcare, and disease prevention. IEEE Trans. Inform. Technol. Biomed. 9:325–336 Park S et al., (2007) Performance Analysis of 802.15.4 and 802.11e for Body Sensor Network Applications. IFMBE Proc. vol. 13, 4th Int. Workshop Wear. & Impalnt. BSN, 9-14 Parkka J et al., (2006) Activity Classification Using Realistic Data From Wearable Sensors. IEEE Trans. Inform. Technol. Biomed. 10: 119-128 Chung-Chih Lin et al., (2006) Wireless Health Care Service System for Elderly With Dementia. IEEE Trans. Inform. Technol. Biomed. 10: 696704 Adlam T et al., (2004) The installation and support of internationally distributed equipment for people with dementia. IEEE Trans. Inform. Technol. Biomed. 8: 253-257 Mihailidis A et al., (2004) The use of computer vision in an intelligent environment to support aging-in-place, safety, and independence in the home. IEEE Trans. Inform. Technol. Biomed. 8: 238-247

11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30.

Schmitt L et al., (2007) Towards Plug-and-Play Interoperability for Wireless Personal Telehealth Systems. IFMBE Proc. vol. 13, 4th Int. Workshop Wear. & Impalnt. BSN, 257-263 http://cordis.europa.eu/fp7/ict/programme/challenge5_en.html Jobbagy A, et al., (2006) Blood Pressure Measurement at Home. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 3319-3322 Spyropoulos B et al., (2006) Development of low-cost Hardware supporting Mobile Home–Care. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 372-375 Demongeot J et al., (2002) Multi-sensors acquisition, data fusion, knowledge mining and alarm triggering in health smart homes for elderly people. C. R. Biologies 325: 673–682 Tamura,T et al., (2006) The ad-hoc Network System for Home Health Care. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 3856-3858 Jovanov E et al., (2005) A wireless body area network of intelligent motion sensors for computer assisted physical rehabilitation. J Neuro Eng. Reh 2:6 doi:10.1186/1743-0003-2-6 Chen W et al.,(2005) Unconstrained detection of respiration rhythm and pulse rate with one under-pillow sensor during sleep. Med Biol Eng Comput 43: 306 312 Lackovic I et al., (2000) Measurement of gait parameters from free moving subjects. Measurement, 27(2): 121-131 Pansiot, J et al., (2007) Ambient and Wearable Sensor Fusion for Activity Recognition in Healthcare Monitoring Systems. IFMBE Proc. vol. 13, 4th Int. Workshop Wear. & Impalnt. BSN, 208-212 Chetelat O et al (2006) Continuous multi-parameter health monitoring system. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 585-588 Wegmueller MS et al (2006) Digital Data Communication through the Human Body for Biomedical Monitoring Sensor. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 608-612 Karantonis D M et al., (2006) Implementation of a Real-Time Human Movement Classifier Using a Triaxial Accelerometer for Ambulatory Monitoring. IEEE Trans. Inform. Technol. Biomed. 10: 156-167 Alic A et al., (2006) A Novel Approach to Wheeze Detection. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng., 963-966 Chuang-Chien Chiu et al., (2006) A Wearable e-Health System with Multi-functional Physiological Measurement. IFMBE Proc. vol. 14, World Congress on Med. Phys. & Biomed. Eng. 419-422 Scanaill C N et al. (2006) Long-term telemonitoring of mobility trends of elderly people using SMS messaging. IEEE Trans. Inform. Technol. Biomed. 10: 412-413 Anliker U et al (2004) AMON: a wearable multiparameter medical monitoring and alert system. IEEE Trans. Inform. Technol. Biomed. 8: 415-427 Ordonez, C (2006) Association rule discovery with the train and test approach for heart disease prediction. IEEE Trans. Inform. Technol. Biomed. 10: 334-343 Keogh E et al., (2006) Finding Unusual Medical Time-Series Subsequences Algorithms and Applications. IEEE Trans. Inform. Technol. Biomed. 10: 429-439 Sovilj S et al., (2005) Continuous Multiparameter Monitoring of P Wave Parameters after CABG Using Wavelet Detector, Proc. Computers in Cardiology, 489-492

Author: Ratko Magjarevic Institute: University of Zagreb Faculty of Electrical Engineering and Computing Street: Unska 3 City: Zagreb Country: Croatia Email: [email protected]

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Modelling and Simulation of Ultrasound Non Linearities Measurement for Biological Mediums R. Guelaz, D. Kourtiche and M. Nadi University of Henri Poincaré, Laboratoire d’Instrumentation Electronique de Nancy, Nancy, France

Abstract— We present an implementation of the nonlinear propagation in an ultrasonic measurement modelling with VHDL-AMS–IEEE-1046-1999 language . The system is dedicated to nonlinear mediums characterization by a compared method measurement. Usual modelling of ultrasonic transducers are based on electrical analogy and are not simulated in the global measurement environment. The ultrasonic transducer modelling proposed is simulated with the nonlinear acoustic load and electronic excitation. The nonlinear B/A parameter is used to characterize medium with a comparative method. The measurement cell is composed of two piezoelectric ceramic transducers which are implemented with the Redwood’s electric scheme. The analyzed medium is placed between the transducers and modeled to take into account the nonlinear propagation with the B/A parameter. The usual transmission line model has been modified to take into account the nonlinear propagation for a one dimensional wave. Results obtained with simulation of mediums characterization with (blood, milk, liver and human fat tissue) showed good a modeling in agreement between modelling and experimental measurement, also a maximum error of about 12.5%. Keywords— Modelling, ultrasound, nonlinear, simulation, propagation, VHDL-AMS.

I. INTRODUCTION The ultrasonic imaging calls upon very advanced technologies in term of high-speed signal processing and conception of ultrasonic transducers matrix in nanotechnology methodology. The useful signal is generally the fundamental frequency of the resonance transducers. However recent studies show the interest of the harmonic frequencies analysis generated by the crossing of ultrasonic waves in biological environments. Works show the improvement of the image quality as in the case of the second harmonic imaging [1]. In addition to the image quality, the measurement method of the nonlinear parameter B/A makes it possible to envisage a mediums characterization. The integration of this parameter in ultrasonic system modelling is an essential stage of the measurement system conception study for multi layer biological environment analysis. Two types of methods make it possible to evaluate the nonlinearity parameter : the thermodynamics methods [2] and the finited amplitude methods [3]. The first is not credible for

in vivo measurement because of the precise variation needed in environmental parameters such as the temperature or the pressure in tissues. The second method is more realist and consists in analyzing the harmonic wave propagation of the ultrasonic signal. The coupling of the various physical natures parts (electronics and acoustics) requires the use of mixed language such as VHDL-AMS IEEE 1076-1999 to determine precisely the influence of each part in the measurement system. Usual modellings of ultrasonic systems use an acoustic model medium assimilated to an electric propagation line without losses [4] and without nonlinear aspect. Our model based on this same theory of electric propagation line integrates the nonlinearity B/A parameter, by a recurrent formulation of the Burger’s equation solution [5]. The measurement system modelling is based on a nonlinear medium excitation by an ultrasonic transducer vibrating at a fixed frequency fo. An identical transducer is placed at the end of the measurement cell and makes it possible to analyse the acoustic wave in the propagation axis of the transmitting source. The electric signal analysis of the receiver transducer is used to identify the acoustic signal at its fundamental frequency and its second harmonic by a fast Fourier transform. Parameter B/A is estimated by a comparative method [6] with water like reference medium and ethanol like analysed medium. The parameter B/A estimation shows a measurement system modelling adapted to the ultrasonic medium characterization study. II. THE MEASUREMENT SYSTEM MODELLING A. The measurement principle of a comparative method The measurement system principle for study the ultrasonic characterization is presented in figure 1. A transducer emits an acoustic wave at a frequency fo through medium. A receiving transducer vibrating at the same frequency fo in a first case is placed at the end of the measuring cell. In a second case, we study the response obtained with a transducer vibrating at 2fo in order to improve the sensitivity measurement. The transducers are assembled with air like backing medium (Rback in figure 1) with acoustic impedance Z = 425Rayl and are stuck in Plexiglas structure.

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wave propagation in a nondissipative medium (without losses) is described below:

d Electric excitation

emission y transducer

ρ ,c0 ,B/A

Ve(t)

P0

t

|Ve(f)|

a o

V0

reception y transducer

Nonlinear Medium:

acoustic wave

P1 P2 a

Vs(t)

z

|Vs(f)|

t

V1 V2

f

f

x

∂u − β .u . ∂u = 0 ∂z co2 ∂τ

Reception signal

f 2f

x

f

With co the acoustic medium celerity, u is the particles velocity and τ = t – z/co, z is the axis propagation. β=1+0.5*B/A is the nonlinear parameter in liquid mediums. In the case of sinusoidal incident wave, the solution of the equation is given by:

Fig. 1 Principle of measurement cell Piezoceramic layer

⎛ ⎞ z u ( z ,t ) =sin⎜ t − ⎟ ⎝ co + β .u ( z,t ) ⎠

Nonlinear Medium Delay (Td)

v2

v1 Zo

Zo

F2

Zback

Fii

F1 Co

I3 R

Ftt

Emitter Co

Piezoceramic layer v1

F1

CScope

RScope

T

(3)

With l = 1/( β*k*M), k = w/co with w the pulsation of the wave in the beginning, M = Uo/co is the Mach number, Uo is the amplitude of the ultrasonic source and σ= β.w.Uo.z/co² the shock formation coefficient. C. Implementation of non linearities in a linear propagation line

v2

Co

The shock front appearance in the wave form is characterized by a coefficient noted σ (0< σ 1 hours

Questions to patient’s accompanier

%

Answers

How often do you see to the patient?

66,7 33,3

> weekly < weekly

How long time do you stay with the patient?

86,7 13,3

2 h per day All the day

Who is your accompany person?

Q. patients and accompany person What’s your familiarity with: mobile phone?

PC?

Do you surf the Internet?

Answers

%Pz

%Acc

93,3

26,7

6,7

73,3

93,3 6,7

26,7 73,3

Scarce Good

0,0

46,7

100,0

53,3

Yes, I do No, I don’t

Poor Very good

IV. CONCLUSIONS The needs analysis shows that the integration of ambulatory follow-up with Home Monitoring improves the Quality of Care by reducing discontinuity in the profile of care. The questionnaires answers analysis shows that patients and their accompaniers welcome integration of ambulatory follow-up with ICT solutions. Costs analysis demonstrates that, under the considered hypothesis, the break even point increases of about few patient’s units. However it is necessary to take in account an education for all actors. Even if the implemented study needs further investigations, it seems preliminary that the integration of traditional ambulatory services with new telematic solutions can increase the satisfaction of different needs without remarkable growth of the costs.

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REFERENCES 1. 2. 3. 4.

5.

6.

7.

8.

9.

10. 11. 12.

Fig. 1 Break even analysis. It refers to an Hospital’s ambulatory dedicated to CHF patients for 12 hours/month for 12 months/year. The results show that the integration of Ambulatory Follow-up with a Web Services for the Home Monitoring implies an average increase of the break even point estimable in 35±2,6% of patients’ numbers.

ACKNOWLEDGMENT The Authors thank the General Directions of Clinica Villalba of Prof. Umberto Bracale for their cooperation and for having given the possibility to carry out all the activity necessary for the case study.

13.

Gronda E, Mangiavacchi M, Andreuzzi B, Municino A. (2002) “A population-based study on overt heart failure”. Ital Heart J 3: 96-103. Comitato Ospedalizzazione Domiciliare, Documento Conclusivo Caratterizzazione dei Servizi di Cure Domiciliari, Roma, 30 settembre 2002, at http://www.ministerosalute.it/. Piano sanitario nazionale 2006-2008, approved by D.P.R. of 0704-2006, published in Gazzetta Ufficiale della Repubblica Italiana n. 139 of 17-6-2006 - Suppl. Ordinario n. 149. Shah NB, Der E, Ruggerio C, Heidenreich PA, Massie BM. (1998) “Prevention of hospitalisations for heart failure with an interactive home monitoring program”. Am Heart J 135: 373378. Bracale M, Cesarelli M, Bifulco P (2004) “An integrated webbased telemedicine solution for ambulatory and home-care assistance and follow up of congestive heart failure and pacemaker patients”, electronic proceeding, Medicon 2004, Ischia, Naples (It). Pecchia L, Bracale M (2006) “A Service via Web for the use of HRV in the follow up of Cardiopath patients”, electronic proceeding, 5th European Symposium on Biomedical Engineering, 7th – 9th luglio 2006, Patrasso (Gr). Pecchia L, Argenziano L, Bracale M (2006), “The need of the follow-up in patients: a useful approach using web services”. IEEE International Conference on Information Technology in Biomedicine (ITAB 2006), electronic proceeding, 26-28 October 2006, Ioannina (Gr). Bonaduce D, Petretta M, Marciano F et al. (1999) “Independent and Incremental Prognostic Value of Heart Rate Variability in Patients with Chronic Heart Failure”. Am Heart J 138 (2):273284. Nolan J, Flapan AD, Capewell S, MacDonald TM, Neilson JM, Ewing DJ. (1992) “Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function”. Br Heart J; 67: 482–5. Malik M, Camm AJ. (1993) “Heart rate variability: from facts to fancies”. J Am Coll Cardiol; 22: 566–8. Hohnloser SH, Klingenheben T, Zabel M, Schroder F, Just H. (1992) “Intraindividual reproducibility of heart rate variability”. PACE 15: 2211–4. Hunt SA, Baker DW, Chin MH, et al. (2005) ACC/AHA 2005 “Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”. Circulation 2005;112;154-235. D.M. Sanità of 22/07/1996, “Prestazioni di assistenza specialistica ambulatoriale erogabili nell’ambito del Servizio Sanitario Nazionale e relative tariffe”, published in Gazzetta Ufficiale della Repubblica Italiana n. 216/96.

Authors: Marcello Bracale; Leandro Pecchia Institute: University Federico II, Department of Electronic Engineering and Telecommunication, Biomedical Engineering Unit Street: Via Claudio, 21 80025. City: Naples Country: Italy Email: [email protected]; [email protected].

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2CTG2: A new system for the antepartum analysis of fetal heart rate G. Magenes1, M.G. Signorini2, M. Ferrario2, F. Lunghi3 1

Dipartimento di Informatica e Sistemistica, Università di Pavia, Italy 2 Dipartimento di Bioingegneria, Politecnico di Milano, Italy 3 S.E.A. Sistemi Elettronici Avanzati, Pavia, Italy

Abstract— The cardiotocography (CTG) has been introduced in in the early ‘70ies as a clinical test for checking fetal well-being during pregnancy and at the moment of delivery. The traditional approach was based on the detection of several time domain parameters of Fetal Heart Rate (FHR) signal starting from the identification of a signal baseline. With the certainty that FHR really contains important indications about potentially dangerous fetal conditions, a prototype system has been setup based on new algorithms and indices which can enhance the differences among normal and pathological fetal conditions. The basic characteristics of this system are: FHR sampled and recorded at 2 Hz; on-line traditional analysis by incremental Mantel algorithm; extraction of accelerations, decelerations, FHR variability and related parameters; extraction of power spectral components related to different physiological control mechanisms; computation of FHR signal regularity indices through the Approximate Entropy algorithm. Keywords— Fetal monitoring, Heart rate analysis, Nonlinear methods.

I. INTRODUCTION Among the clinical tests performed in the antepartum period to assess the functional wellbeing of the fetus, the Cardiotocography (CTG) represents one of the most diffused methods to investigate fetal condition in a non-invasive way. Although the CTG has led to a drastic reduction of intrapartum and precocious child mortality, some recent studies have pointed out that very poor indications about fetus/newborn illness could be inferred from the actual CTG analysis [1]. This conclusion is apparently contradicted by the fact the most reliable indicator of fetal condition is the FHR signal, upon which CTG is based. Most current clinical interpretations of FHR signal, although with some minor differences, consider the presence of a sinusal rhythm of the FHR (baseline), on which the physiological control mechanisms generate some frequency changes in the heart activity. These changes or events are identified as accelerations and decelerations [2]. Up to now, the basic idea in automatic CTG analysis has been the extraction of the baseline, followed by the detection of the above mentioned events, considering and measuring some morphological signal characteristics in the same way as the

clinicians do by eye inspection. The automatic classification of fetal states proposed by some commercial CTG systems (Sonicaid System 8002, OB Tracevue, old 2CTG), is designed to match these criteria [3, 4]. As a further improvement, estimation of the short term (STV) and long term (LTV) variability characteristics has been considered. Other parameters such as Interval Index and Delta, have been derived from the previous ones in order to reinforce this statistical signal analysis [4]. The algorithmic approaches proposed so far did not lead to significant clinical improvements with respect to a qualitative analysis performed by an expert clinician, except for a reduction of the intra and inter-observer variability [5]. The scoring systems based on morphological and time domain parameters, aimed at providing some guidelines in the FHR signal reading and classification, are still lacking of reliability if the purpose is to calculate figures and to relate these figures to fetal outcome [1]. The goal of the present paper is to describe the implementation of an automatic analysis system for the fetal heart rate signals which integrates information coming from the morphological and time domain traditional approaches, from frequency domain analysis based on autoregressive estimation and, finally, from non linear analysis. The software design aims at improving the clinical monitoring by providing analysis tools, which implement advanced signal processing techniques in order to better classify fetal conditions. II. MATERIALS AND METHODS A. The computerized cardiotocographic system Because of its great diffusion in clinical prenatal fetal monitoring we decided to adopt a classical ultrasound based CTG for our FHR analysis. A numerical (or computerized) cardiotocographic (2CTG) system is composed by two devices: a cardiotocograph, which records fetal heart rate and the toco signal and a microprocessor system which analyzes and stores those signals. The two parts can be physically separated, as in our case where we acquired numerical data from a stand-alone fetal monitor equipped with a serial interface (or a Bluetooth) communicating with a PC.

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In our system we can use all CTG fetal monitors compatible with the HP data protocol (HP series 135X, Corometrics 170, Philips 50A, ...), provided with a serial link. These fetal monitors use an autocorrelation technique to compare the demodulated Doppler signal of a heartbeat with the next one. Peak detection software then determines the heart period (the equivalent of RR period) from the autocorrelation function. With a peak position interpolation algorithm, the effective resolution is better than 2 ms [6]. The resulting heart period is then converted into a heart frequency as soon as a new heart event is detected and accepted. Due to historical reasons, almost all commercially available fetal CTG monitors display only the fetal heart rate expressed in number of beats per minute (bpm). The HPlike monitors produce a new FHR value in bpm every 250 msec and store it in a buffer. In the commercially available systems (e.g. OB TraceVue), the computer reads 10 consecutive values of the buffer every 2.5 sec and determines the actual FHR as the average of the 10 values. In our 2CTG2 system, the software reads the FHR from the buffer at 2 Hz, allowing an increase of FHR Nyquist frequency up to 1 Hz. The choice of reading the FHR values each 0.5 sec represents a reasonable compromise to achieve enough bandwidth and an acceptable accuracy of the FHR signal. B. Signal Recording & Preprocessing If compared to standard Holter recordings, the buffering procedure highly reduces the precision of the RR sequence as generated by inverting the FHR signal (60000/FHR ms). Besides, the CTG device can erroneously lock on the slower maternal heartbeat, even when the autocorrelation method is employed. This leads to an abrupt decrease into the FHR signal and it influences the evaluation of variability indices. Therefore, a proper artifact detection technique has to be employed. The one we developed relays on the work of van Geijn et al. [1980]; the main concept is that an acceleration of heart rate develops more slowly than a deceleration does, thus the limit for the acceptance of the point S(i +1) differs according to whether S(i + 1) is smaller or greater then S(i). In details, three requirements are set up: (i) acceptance of FHR values which satisfy the criterium: 200 S (i ) 200 S (i ) < S (i + 1) < 400 − S (i ) 114 + 0.43S (i )

(1)

The whole series is processed many times and, at each run, the number of points rejected is counted; the process stops when in a entire run no further points were discarded; (ii) a minimum of three intervals that qualify to (1) must be present in succession (S(i - 1), S(i) and S(i + 1) for final acceptance of S(i+1)); (iii) short intervals of valid points,

contained between invalid sequences, are rejected if their length is equal or smaller than 20 points. Ranges for acceptance of S(i + 1) are comparable with those applied in commercial monitors (= S(i) ± 20 bpm). Nevertheless the applied criterion is definitely more selective and precise. A quality index quantifies three different levels of the FHR signal (optimal, acceptable and insufficient quality). The evaluation is based on the output of the autocorrelation procedure implemented in the HP1351A. Each FHR series underwent a subdivision into 3-minutes segments (360 points) after removing the bad quality points at the beginning of the sequence. C. Analysis parameters After being preprocessed, the CTG signals undergo to the analysis procedure. The software computes a set of standard parameters related to the morphology of the signal (baseline, large and small accelerations per hour, decelerations per hour and contractions per hour) and to the time domain characteristics of FHR (FHR mean over a minute, FHR standard deviation, Delta FHR, Short term variability (STV), Long term irregularity (LTI), Interval Index (II)) as reported in [4]. The novelty resides in the computation of frequency domain indices and of regularity/non linear parameters, following the results of our research group [7,8]. In particular, among the regularity and nonlinear parameters, the Approximate Entropy (ApEn) [9] is included in the standard clinical version. In the research versions of our software we implemented some new nonlinear indices: Detrended Fluctuation Analysis (DFA) [10]; Muliscale Entropy (MSE) [11], Lempel Ziv Complexity (LZC) [12] D. Software implementation The 2CTG2 can be classified in an intermediate position between a software tool for retrieving, analyzing and storing data from a CTG medical device and a stand alone solution to handle a variety of data regarding the whole pregnancy period. This is mainly because it offers both the functionalities. The main goal while developing the 2CTG2 software was indeed to achieve the maximum number of features without loosing lightness and simplicity. The 2CTG2 was built with the Microsoft Visual C++ IDE and was designed to run on any of the Windows platforms, from Windows 98 to the newest XP Pro versions. The application was divided in two main modules: the main interface and the mathematical library. The first is based on the Microsoft Foundation Classes and offers a simple user interface to handle the signals as well as the patient personal and anamnestic information. The second is a collection of highly optimized signal processing algorithms implemented

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in ANSI C and C++ routines. Considering in deeper detail the approach used in developing the solution, it is remarkable that the application is subdivided into three tiers: the data tier, the application tier and the user interface tier, according to the Windows DNA paradigm. The data tier consists of a set of classes that perform data extraction and handling from the database source. The application tier, also known as the “business logic”, is the real added value of the 2CTG2, being composed by the analysis and data manipulation modules. The user interface tier is the “presentation” layer that is the component designed to interact with the user. The data layer was written to communicate with a Microsoft Access database. Anyway, the application doesn’t need Access to be fully installed on the operating system: it only needs the Microsoft Jet Engine, which is lighter and freely distributable. Dividing the data tier from the business logic made the 2CTG2 easily extendable and flexible in event of changes in the data structure or for future releases requirements. The 2CTG2 interacts with the database using SQL queries, so the data tier can be considered as an interface layer between the application layer and potentially any relational database that supports the SQL language. By

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simply extending this layer or just substituting with another implementation, the 2CTG2 will be able to connect to local and remote DBMS such as Oracle, MS SQL Server or mySQL, but no changes will be needed in the application and presentation layer. Another sub-module in the data tier is the file I/O layer. This module is a set of classes able to load and store patient and medical information in various file format in order to achieve the maximum compatibility and to allow data exchange between various sources. The 2CTG2 software can read and write files compatible with OBTraceVue, old versions of 2ctg, Matlab, and Excel. The second and most important tier is the application tier. It consists of a set of functionalities to manage the data provided by the data layer or directly coming from the connected medical device. The business logic contains the module responsible for the connection with the cardiotocograph. This was developed in a multithreaded way to take advantage of the modern operating system time sharing capabilities. The 2CTG2 software is designed to perform real time data acquisition and analysis while continuing offering the user a fully functional interface.

Actions

Parameters

CTG tracings

Fig. 1 The 2CTG2 graphical interface, with two comtemporary recordings coming from two different CTG monitors.

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This allows the user to perform the data acquisition from the cardiotocograph while storing patient’s personal data or even retrieving and analyzing old exams. Moreover, the software makes possible to acquire simultaneously as many traces as cardiotocographs are connected, through the identification of the CTG device. Both the analysis and data acquisition modules were developed considering the need of an almost immediate response. In a standard case (1 hour of trace) the analysis and the graphical representation of the output are performed within the refreshing frame rate of the video (20 ms). The third layer is the user interface and it was developed, as already told, using the Microsoft Foundation Classes (a set of classes to create standard Windows interfaces). It is a Multiple Document Interface, so it can offer the user many traces loaded and presented simultaneously, even during the acquisition process. Moreover a user can compare different tracks of the same trace by opening multiple views of the same exam. The main trace window needs a special mention: it displays the trace and let the user scroll it when reviewing. It was built trying to reproduce the cardiotocograph paper roll. Consequently, at a proper monitor resolution there is a perfect match between a centimeter drawn on the computer display and a centimeter printed out on the paper. A zoom command will scale the drawing but will maintain image ratios so that the trace will never appear deformed on the screen, in order to avoid misinterpretation of acceleration and contractions by the physician. The user interface contains also a group of printing possibilities, such as a compact print, a detailed print and a complex print of the analysis results. III. RESULTS AND CONCLUSIONS The 2CTG2 software has been extensively tested mainly in two OB-Gyn University Clinics in Rome and Naples (Prof. D. Arduini and Prof. A. Di Lieto) over more than 2000 cases. Each recording lasts at least 60 min, in order to include both activity and quiet periods of the fetus. For the majority of cases it has been possible to collect the full patient information, consisting of CTG recording date, gestational age, diagnostic indication at CTG date, identification of fetal sufferance, type of delivery, date of delivery, diagnosis at birth and Apgar scores. The software has been used for discriminating IUGR suffering fetuses from normal [7]. It also identifies severe IUGRs from small for gestational age (SGA) fetuses [8]. The 2CTG2 software is a well tested medical reality since it is used in many italian obstetric departments after a wide clinical test phase. This application seems to have reached its two main goals in terms of ease of use as a medical device integration

software and scientific contribution as it computes a detailed analysis on tracings without losing speed and simplicity. So, after a few years since the development of this tool begun, we can considering the 2CTG2 as a light but complete software that implements the features needed by a nurse who wants to perform a CTG exam in a crowded obstetric ward on a pregnant woman and a solution for the doctor who wants to perform a complex real-time analysis on the recording showing mathematical parameters for helping the diagnostic process. Research is still in progress and new features concerning non linear parameters (DFA, MSE, LZC) will be implemented on a new release of the software, as well as advanced classifiers. The future for this tool is to increase its scientific interest by performing different kinds of analyses and to enhance its power in detecting parameters related to illness states.

REFERENCES 1.

van-Geijn-HP(1996), Developments in CTG analysis. Baillieres-ClinObstet-Gynaecol.; 10(2): 185-209. 2. Mantel R., Van Geijn HP, Caron FJM et al (1990), Computer analysis of antepartum fetal heart rate, Int J Biomed Comput, 25, 261-272. 3. Dawes GS, Moulden M, Redman CW (1995) Computerized analysis of antepartum fetal heart rate, Amer. J. Obstet. Gynecol.,173, 4, 1353–1354, 1995. 4. Arduini D, Rizzo G et al (1993), Computerized Analysis of Fetal Heart Rate: I. Description of the System (2ctg), Matern. Fetal Invest. 3, 159-163. 5. van Geijn HP, Lachmeijer AM, Copray FJ (1993) European multicentre studies in the field of obstetrics, Eur J Obstet Gynecol Reprod Biol. 50, 1, 5–23. 6. Fetal Monitor Test—A Brief Summary, Hewlett-Packard, Boeblingen,Germany, 1995, pp. 1–6. 7. Signorini MG, Magenes G, Cerutti S, Arduini D (2003), Linear and Nonlinear Parameters for the Analysis of Fetal Heart Rate Signal from Cardiotocographic Recordings, IEEE Trans Biom Eng, 50(3), 365-374. 8. Ferrario M, Signorini MG, Magenes G, Cerutti S (2006) Comparison of entropy based regularity estimators: application to the Fetal Heart Rate signal for the identification of fetal distress, IEEE Trans Biom Eng,3,1, 119-125. 9. Pincus SM (1995), Approximated entropy (ApEn) as a complexity measure, Chaos, 5 , 110-117. 10. Peng CK,. Havlin S, Stanley HE, Goldberger AL (1997) Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series, Chaos, 5, 82–87. 11. Costa M, Goldberger AL,. Peng CK (2002), Multiscale Entropy Analysis of Complex Physiologic Time Series, Phys. Rev. Lett. 89 (6). 12. Lempel A, Ziv J (1976) On the complexity of finite sequences, IEEE Trans.Inf. Th, 22, 1, 75-81. Author: Institute: Street: City: Country: Email:

Giovanni Magenes Dipartimento di Informatica e Sistemistica Via Ferrata 1 27100 Pavia Italy [email protected]

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Cardiac arrhythmias and artifacts in fetal heart rate signals: detection and correction M. Cesarelli, M. Romano, P. Bifulco, A. Fratini Dept. of Electronic Engineering and Telecommunication, Biomedical Engineering Unit, University "Federico II", Naples, Italy Abstract— Cardiotocography is the most commonly used noninvasive diagnostic technique that provides physicians information about fetal development (in particular about development of autonomous nervous system - ANS) and wellbeing. It allows the simultaneous recording of Fetal Heart Rate (FHR), by means of a Doppler probe, and Uterine Contractions (UC), by means of an indirect pressure transducer. Currently, in cardiotocographic devices, Doppler methodology involves autocorrelation techniques to recognize heart beats, so evaluation of inter-beats time-interval is very improved. However, recorded FHR signals may contain artifacts, because of the possible degradation, or even less, of the Doppler signal due to relative motion between probe and fetal heart, maternal movements, muscle contractions and other causes. Moreover, fetal cardiac arrhythmias can have an effect on FHR signals. These arrhythmias do not represent an expression of the physiological behavior of the ANS. Both, artifacts and cardiac arrhythmias represent outliers of the FHR signals, so they affect both time domain and time frequency signal analysis. Their detection and correction is therefore necessary before carrying on signal processing. In this work, an algorithm for detection and successive correction of outliers (signal artifacts and fetal cardiac arrhythmias) was developed and tested, both on simulated FHR series and real FHR series. Keywords— fetal cardiac arrhythmias, local outliers, global outliers, median filter.

I. INTRODUCTION Cardiotocography (CTG) is the most diffused indirect diagnostic technique to monitor fetal health during pregnancy and labor and it is the only medical report to have legal value in Italy. It allows the simultaneous recording of Fetal Heart Rate (FHR) and Uterine Contractions (UC). CTG provides physicians information about fetal development and well-being; particularly, CTG permits to assess maturation of Autonomous Nervous System (ANS) of the fetus [1]. To assess fetal health and reactivity, clinicians evaluate specific signs of the FHR signal and, during labor, they pay also attention to shape, intensity and frequency of UC, correlating them to changes induced in FHR. The efficiency of this method, depending on the expertise of the observer, lacks of objectivity and reproducibility [2].

The general target of our research is to develop objective and quantitative analysis methods (both in time domain and in frequency domain) for physicians decision support. It is well known that, in adults, the HR Variability (HRV) is a noninvasive and quantitative means to investigate ANS activity (both in physiological and pathological conditions). Also for the fetus, the FHR Variability (FHRV) around its baseline could be a base for a more objective analysis [3] and for a better knowledge of ANS reactions. It is worth remembering that to record FHR signal a US Doppler probe is used. Currently, Doppler technique involves autocorrelation techniques to recognize heart beats, so evaluation of inter-beats time-interval is very improved. However, recorded FHR signals often result noisy and may contain artifacts, because of the possible degradation, or even less, of the Doppler signal due to relative motion between probe and fetal heart, maternal movements and other causes (in fact the device continuously provides an estimate of the signal quality level). Moreover, fetal cardiac arrhythmias, as premature supraventricular depolarizations, premature ventricular depolarizations, non conduced premature supraventricular depolarizations, parasystole [4] and others can have an effect on FHR signals. These arrhythmias do not represent an expression of the normal behavior of the ANS and for their study specific techniques, as 2D echography, blood flows measurements, are usually employed. Both, artifacts and cardiac arrhythmias represent outliers of the FHR signals so they affect both time domain and time frequency analysis. Their detection and correction is therefore necessary. In this work, an algorithm for detection and successive correction of outliers (signal artifacts and fetal cardiac arrhythmias) was developed and tested. II. MATERIAL AND METHODS A. Outlier definition Statistically, an outlier is a data point that is an unusual observation or an extreme value in the data set which deviates so much from other observations as to arouse suspicion that it was generated by a different mechanism [5, 6].

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This above can be considered a general definition of outlier, but it’s necessary a more specific and quantitative definition to detect outliers in the FHR signal. For this purpose, a recent formal definition can be used. This definition is distance based because it considers the distance between the object (which could be an outlier) and other objects of data set as follows: an object p in a dataset D is a (pct, dmin)-outlier if at least percentage pct of the objects in D lies greater than distance dmin from p [6]. Of course it’s necessary to introduce a metric to express distance. However, using this definition it is possible to capture only some kinds of outliers; since the definition takes a global view of the dataset, these outliers can be considered as “global” outliers [6]. For many datasets which exhibit a more complex structure, another kind of outliers has to be considered. Objects that are outlying relative to their local neighborhoods, particularly with respect to the densities of the neighborhoods. These outliers are regarded as “local” outliers [6].This feature is particularly important in FHR signals, so to detect local outliers in FHR signal a working definition of outlier can be used, as follows, introducing the concept of time dependant outlier. A time dependant outlier is a data point that is an unusual observation or an extreme value in the data set, which is not part of a time trend. As time trend we consider two or more consecutive data points which move in the same general direction within a given statistical range [5]. Typically, in FHR signals, cardiac arrhythmias and shorttime artifacts look as local outliers, while signal less appears as global outliers. Therefore, the proposed algorithm uses both working definition and formal distance based one for detection of local and global outliers.

M. Cesarelli, M. Romano, P. Bifulco, A. Fratini

the occorence of ectopic beats, missed beats, bigeminal and/or trigeminal pattern and cambinations of these arrhythmias. Examples of artificially generated FHR series are shown in the figure 1.

B. Simulated FHR signals To test the developed algorithm, synthetic FHR signals were artificially generated, via software, using a slightly modified version of a method proposed by other authors [7]. Following that procedure, an artificial R-R tachogram with specific power spectrum characteristics is generated. The following model parameters were adapted to resemble real fetal cases. LF and HF bands of the FHRV power spectrum were considered to lie between 0.04 and 0.2 Hz, and 0.2 – 1 Hz, respectively. LF/HF power ratio was fixed to 5 and Standard Deviation of HF band to 0.03. Mean FHR was initially set at 140 bpm (within the range of normality, 120160 bpm). Then, a variable SD was considered, it was set at 1 in the first part of the signal, at 4 in the second part and at 2 in the last part. In addition, to obtain signals resembling other conditions, we simulated also some typical and frequent fetal cardiac arrhythmia. For example, we simulated

Fig. 1 examples of artificially generated FHR series.From the top: # 6 resembles physiological conditions; # 7 resembles 13 PVD’s (Premature Ventricular Depolarizations); # 25 resembles examples of Bigeminism (a zoom is proposed immediately below). #27 resembles PVD’s and missed beats All the numbers are referred to an internal numbering All simulated FHR signals had a duration of 25 minutes.

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C. Real CTG signals We carried out other tests using real FHR signals. In this case, CTG traces were recorded in clinical environment during the normal daily practice from women (singleton physiological pregnancies), who did not take drugs, close to delivery (33–42 gestation weeks). Apgar scores, birth weights and other information were collected in order to involve only CTG regarding healthy fetuses in the analysis. CTG recordings have an average duration of about 30 minutes. CTG recordings with evident artifacts or fetal cardiac arrhythmias (recognized with the support of a medical team) were chosen for the analysis. D. Algorithm description The algorithm is included in a software for CTG preprocessing, developed at our lab., which segments each recorded signal into a number of reliable continuous tracts (i.e. where the signal quality level is acceptable or good); with an opportune procedure (see in the following) removes possible outliers and then replaces unreliable signal tracts of less than 4 seconds with linear interpolated values. Finally, re-interpolating and re-sampling the values at a frequency of 4 Hz, an output FHR signal uniformly sampled and aligned with UC (within 0.25 sec) is obtained. Regard the procedure to remove outliers (algorithm developed in this work), it consists in two main steps: detection and correction. Detection phase, in order to be more robust, following some examples reported in literature, is based on a double scanning of the FHR signal. In forward scanning, every sample of FHR which differs by more than an assigned threshold from the median computed on the previous 5 samples, is marked as “candidate outlier”. In backward scanning, instead, every sample of FHR which differs by more than an assigned threshold from the median computed on the following 5 samples is marked as “candidate outlier”. In our algorithm, threshold is fixed at 12 bpm for samples of good or acceptable quality, otherwise it is fixed at 6 bpm (both values were heuristically chosen). The length of median filter was chosen equal to 5 in order to have a result certainly not dependent on until 2 outliers out of 5 samples. Every sample of FHR signal marked as a candidate outlier both in forward scanning and in backward scanning is treated as a real local outlier. At this point, the algorithm looks for global outliers. As first step, it checks if it is possible to detect two groups of at least 4 consecutive local outliers lying on opposite slope tracts of FHR signal (let us call them “guard groups”). The samples

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between the guard groups are considered candidate global outliers. The algorithm applies the formal distance based definition considering as outliers every sample which differs by more than 40 bpm from 95% of all samples of FHR signal. If this definition is matched, the algorithm searches the first sample (A) not marked as candidate outlier coming before the first guard group and the first sample (B) not marked as outliers following the second guard group. All samples between A and B are considered as real outliers. Correction phase is realized, for local outliers, by replacing outliers whit the result of a fifth order median filter temporally centered on outlier itself. For global outliers, the algorithms realizes a linear interpolation from the first valid sample preceding first guard group and the first valid sample following second guard group. All corrected tracts are marked on the CTG trace. III. RESULTS The performances of developed algorithm were assessed on 200 simulated FHR signals (whit a random insertion of most common fetal arrhythmias and some their combination) and on 25 real FHR signals. As example, the following figures show some results. In all tested cases, algorithm showed satisfactory performances; in fact, it is able to detect and correct all outliers due to arrhythmias and/or artifacts for simulated and real FHR signals.

Fig. 2 examples of results obtained with the developed algorithm. From the top (simulated FHR series): 7-bis: FHR series # 7, reported in fig. 1, after correction of outliers. 25-bis: FHR series # 25, reported in fig. 1, after correction of outliers.

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The developed algorithm is a non linear algorithm which consists of two principal steps, detection and correction, to find outliers and to replace them whit samples which simulate the normal ANS control on cardiac rate. Detection phase is based on double scanning of FHR series whit two different thresholds while, for correction, a fifth order median filter is used for local outliers and a linear interpolation is used for global outliers. The algorithm showed satisfactory performances in all test using both simulated and real FHR signals. However, to test the algorithm on a more numerous set of real FHR signals and involving other conditions can be very useful.

ACKNOWLEDGMENT The Authors would like to thank ing. Giuseppe Longobardi for his kind and precious collaboration.

REFERENCES 1. 2.

3.

Fig. 3 examples of results obtained with the developed algorithm. From the top (simulated FHR series): FHR series whit global outliers; zoom on global outliers; FHR series after correction.

4. 5. 6.

IV. CONCLUSION In FHR signals can be anomalous samples due to cardiac arrhythmias and/or artifacts. These samples represent outliers because they are not correlated whit normal ANS behavior. Outliers affect time domain analysis and frequency domain analysis of FHRV, so their detection and removal is necessary. Nevertheless, their impulsive nature makes impossible to use a linear filter to remove them.

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M.G.Signorini, G.Magenes, S.Cerutti, D.Arduini (2003) Linear and nonlinear parameters for the analysis of fetal heart rate signal from cardiotocographic recordings. IEEE Trans.Biomed.Eng.50(3):365-75 F.Figueras, S.Albela, S.Bonino, M.Palacio, E.Barrau, S.Hernandez, C.Casellas, O.Coll, V.Cararach (2005) Visual analysis of antepartum fetal heart rate tracings: inter- and intra-observer agreement and impact of knowledge of neonatal outcome. J Perinat Med.; 33 (3): 241-5 O.Sibony, J.P.Fouillot, M.Benaoudia, A.Benhalla, J.F.Oury, C.Sureau, P.Blot (1994) Quantification of the heart rate variability by spectral analysis of fetal well-being and fetal distress. Europ. J Obstet. & Gynecol. and Reproductive Biology, 54:103-108 M.L.Cabaniss, D.Karetnikov. Fetal monitoring interpretation. Lippincott Company D.N.Lebrun (2003) Analysis of neonatal heart rate variability and cardiac orienting responses. Thesis. Master of Engineering. University of Florida M.M.Breunig, H.P.Kriegel, J.Sande (2000) LOF: Identifying densitybased local outliers. ACM P.E.Mcsharry, G.D.Clifford, L.Tarassenko, L.A.Smith (2003) A dynamical model for generating synthetic electrocardiogram signals. IEEE Trans. on Biom. Eng. vol. 50, no. 3 Author: Prof. Mario Cesarelli Institute: Street: City: Country: Email:

Department of Electronic and Telecommunication via Claudio, 21 Naples Italy [email protected]

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Complexity Analysis of Heart Rate Control Using Symbolic Dynamics in Young Diabetic Patients M. Javorka1, Z. Trunkvalterova1, I. Tonhajzerova1, J. Javorkova2 and K. Javorka1 1

Comenius University, Institute of Physiology, Jessenius Faculty of Medicine, Martin, Slovakia 2 Clinic of Children and Adolescents, Martin Teaching Hospital, Martin, Slovakia

Abstract— Cardiovascular dysregulation and autonomic neuropathy are common complications of diabetes mellitus (DM). Although autonomic neuropathy is considered as one of the late complications of DM, there are some sensitive methods, that can detect autonomic nervous system dysregulation even in early phases of DM. There is ongoing effort to apply methods based on nonlinear dynamics to improve the description and classification of different cardiac states. The aim of this study was to find out which of the heart rate variability parameters of symbolic dynamics are different in young patients with DM compared to control group. Several parameters based on 4 symbols encoding were used for quantification of heart rate variability and complexity. Our results suggest slightly reduced complexity (expressed by marginally nonsignificantly reduced number of “forbidden words”) even in young diabetic patients pointing out to another aspect of heart rate dysregulation in this group. In addition we have found qualitative difference in distribution of symbolic words expressed by parameter “wpsum02”. Parameters of symbolic dynamics could be used (in combination with traditionally used linear HRV measures) for describe additional information in heart rate time series in patients with dysregulation. Keywords— Heart rate variability, nonlinear dynamics, complexity, symbolic dynamics, diabetes mellitus.

I. INTRODUCTION Cardiovascular dysregulation and autonomic neuropathy are common complications of diabetes mellitus (DM). It is very important to diagnose the cardiac dysregulation, because there is a significant relationship between the autonomic nervous system and cardiovascular mortality, including mortality of patients with this type of complication [1,2]. Although autonomic neuropathy is considered as one of the late complications of DM, there are some sensitive methods, that can detect autonomic nervous system dysregulation even in early phases of disease [3,4,5,6]. Although multicentric study EURODIAB have found the presence of cardiac autonomic neuropathy in 19% of diabetics in the age group 15 – 29 years [7], relatively few studies were focused on autonomic neuropathy in young adults with DM type 1.

For diagnosis of cardiac autonomic neuropathy, the Ewing battery of cardiovascular tests or conventional time and frequency domain heart rate variability (HRV) methods are usually used [8]. The reduction of spontaneous HRV is regarded as one of the early signs of the cardiac autonomic neuropathy [3]. The traditional techniques of data analysis in time and frequency domain are rather simple, take a little time, but they are often not sufficient to characterize the complex dynamics of heart beat generation. Therefore, there is ongoing effort to apply methods based on nonlinear dynamics to improve the description and classification of different cardiac states [9]. The aim of this study was to find out which of the HRV parameters of symbolic dynamics are different in young patients with DM compared to control group. II. METHODS A. Subjects In this study, we have included a sample of 34 patients subdivided into two groups. The first group (DM) consisted of 17 patients with type 1 DM (10 women, 7 men) aged 12.9 – 31.5 years (mean ± SEM: 22.4 ± 1.0 years). The mean duration of DM was 12.4 ± 1.2 years. The second group (Control) consists of 17 healthy gender and age matched probands (mean age: 21.9 ± 0.9 years). All subjects gave their informed consent prior to examination. Subjects were instructed not to use substances influencing cardiovascular system activity (coffeine, alcohol) and not to smoke prior to examination. All subjects were investigated in quiet room from 8 to 12 AM. The device VariaCardio TF4 (Sima Media, Olomouc, Czech republic) was used for continuous beat-to-beat monitoring of heart rate. This device consists of thoracic belt with intergrated electrodes. ECG signal was telemetrically transfered into PC for subsequent analysis for detection of R waves and derivation of R-R intervals time series. During measurement, subjects were under standardized conditions (supine position, rest, same time, place) for 60 minutes. We have asked the probands to avoid voluntary movements and speaking as much as possible.

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Fig. 1 Between-groups comparison for parmater “wpsum02”. Bars and error bars indicate groups means and SEM, respectively

Fig. 2 Between-groups comparison for parameter “Shannon entropy” Bars B. Data analysis The HRV analysis was performed off-line using special software on one time interval of R-R interval time series. This segment (denoted in figures as T) consisted of 3200 RR intervals (1st to 3200th R-R interval). The concept of symbolic dynamics is based on coarsegraining of the dynamics. The time series was transformed into symbol sequences with symbols from a given alphabet. Transformation of analysed interval (T) into a symbolic sequence was done as follows: The R-R intervals time series x1, x2, x3......xN was transformed to symbol sequence s1, s2, s3......sN, where si is from the set A, on the base of alphabet A = {0, 1, 2, 3}. Symbol si equals to 0, if xi > µ and xi ≤ µ + SD; symbol si equals to 1, if xi > µ + SD and xi < ∞; symbol si equals to 2, if xi > µ SD and xi ≤ µ; symbol si equals to 3, if xi > 0 and xi ≤ µ SD, where µ refers to mean lenght of R-R interval and SD is standard deviation of analysed time series [10]. There are several quantities that characterize such symbol strings. Parameter “forbidden words” is a number of words, which never occur in the distribution of words with the length of 3 symbols. A high number of forbidden words represents more regular and less complex behavior of respective time series (or system). If the time series is rather complex only a few forbidden words can be found. Parameters based on information theory are usually used to describe the distribution of words. We have computed Shannon entropy using following formula: Shannon Entropy = -∑ [p(i) log2p(i)] where p is a probability of given word occurrence. The sum is computed over all possible words (in our case 43 = 64 types of words). Larger values of Shannon entropy refer to higher complexity in respective time series. The other computed parameter was “wpsum02” – percentage of words consisting only of symbols “0” and “2” [11].

and error bars indicate groups means and SEM, respectively

Fig. 3 Between-groups comparison for parameter “forbidden words”. Bars and error bars indicate groups means and SEM, respectively

C. Statistics Because of Gaussian distribution of all assessed parameters, between groups comparison were performed using two-sample t-test. Values p Ptm’ k2 >0 R3 = k3

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Index 1, 2 and 3 denote the distal, intermediate and proximal segments, respectively. Parameter k1 is the reciprocal of the conductance to volume ratio in the distal segment. It was assumed that the linear relationship between the airway conductance and the lung volume, which has been reported by others, mainly reflects changes of airway conductance with the state of lung expansion in small bronchi (distal segment in the model). The value of k1 used in the present study was obtained from the literature [1,4]. The value of k2 cannot be obtained experimentally and is therefore assumed.

[l/s] k3

6

0.5 2

.

4

6

V 2

0

10

20

30 [cmH2O]

Palv

Fig. 3. Effects of increasing k3 on IVPF curve.

II. STATIC ANALYSIS OF THE MODEL The analysis of the model was carried out under the static and dynamic conditions. The term “static” is used here for those conditions, where the time is neglected and the term “dynamic”, for those conditions, where time factor is introduced. The static behaviour of the model was carried out, in most cases, with at least one of the model parameters constant. This is to avoid the complex graphic presentation of a three-dimensional diagram and also to better understand of the physiological mechanisms of the pressure-flow-volume relationship. For instance, to obtain IVPF (isovolume- pressure-flow) curves, the lung volume was held constant. Figure 2 shows a typical IVPF diagram obtained from the model. Preliminary trials disclosed that in order to obtain the IVPF curve, which is consistent with values of Qmax and Palv' experimentally observed in normal persons, with a normal time constant, the value of Ptm’ must be –5cmH2O. However, it has not to be made such a simplified assumption. In other factors, such as traction forces in the surrounding tissues, elasticity, or smooth muscle tone, affect on the airway wall, the actual transmural pressure at the locus of airway narrowing cannot be specified. In the model

which has been considered, this Ptm’ was assumed to remain unchanged at different lung volumes; a constant value has been ued in the following experiments. The dotted line in Fig.2 is the IVPF curve obtained from the model, if Ptm’ is set near zero. In this case, the observed values of Vmax (=Qmax) and Palv’ both were too low. If flow through the airway is assumed to be turbulent the pressureflow relationship is curvilinear until Qmax is reached. The value of Qmax was slightly lower and the value of Palv’ was higher than with the assumption of the laminar flow. Preliminary trials also disclosed that the value of k2 must be more than 20. If a value less than 20 is used, the IVPF curve does not show any plateau, as it is shown by the broken line in Figure 2. This may suggest that in the model, 1cmH2O of positive transmural pressure is associated with an increase of more than 20cmH2O/l/s resistance in the intermediate segment. The effect of increasing downstream resistance (k3) was also tested; the results are shown in Figure 3. There was no

[l]

[ ]

[[ ]

[l]

[l/s] K2 < 20

6

Ptm’ – 5cmH2O

. V 2

Ptm’ – 0cmH2O 0

10

20

[ ]]

[

]

30 [cmH2O]

Palv

Fig. 2. Effects of Ptm’ and k2 on IVPF curve.

Fig. 4. IVPF curves at different lung volumes. A: normal; k1=6, Pst(l) =20cmH2O at TLC (total lung capacity). B: obstructed; k1=12, Pst(l) =10cmH2O at TLC.

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[

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]

B

A

V[l]

Palv

10 cmH2O

V

1l

[l] [cmH2O]

.

V

Fig. 5. A: Relationship between alveolar pressure at the moment that the airway narrows (Palv’) and upstream B: Relationship between the lung volume at the moment that the airway narrows (V’ ) and the upstream resistance (k1) at constant Palv’.

effect on Qmax but a significant effect on Palv’. At a given k1, Palv’ is higher when k3 is increased. This suggests that the airway is less collapsible when k3 is high. With values of Ptm’ = -5cmH2O and k2 = 20, IVPF curves at different lung volumes were computed in the model; the results are shown in Figure 4. It may be seen that there is a linear relationship between the alveolar pressure and the flow until Qmax is reached. As soon as the airway starts narrowing, there is no further increase of expiratory flow even though the driving pressure is further increased. Figure 5A shows the effect of increasing upstream resistance (k1 in the model) on Palv’ . It demonstrates that at a constant lung volume, airway narrowing (in k2) occurs at lower alveolar pressures as k1 is increased. Since alveolar pressure reflects the breathing effort, another way of expressing this is that the higher k1, the less the effort at which k2 collapses. Figure 5B illustrates the same data, with Palv’ instead of volume as a parameter. It may be seen that as k1 is increased, V’ decreases. This suggests that with the same effort (fixed Palv’ ) the airway collapses at a higher lung [cmH2O] 50 Palv 25

0

1

2

3

[s]

time

Fig. 6. Assumed pattern of alveolar pressure for forced expiration.

0

1

2 time

3

[s]

0

1

2

1l/s

3

[s]

time

Fig. 7. Expired volume, flow rate and alveolar pressure plotted against time; forced expiration. A - normal, B - obstructed.

volume can thus be interpreted to represent an effective alveolar pressure generated by the respiratory muscles, in the sense that any energy spent on increasing the alveolar pressure beyond Palv’ is wasted as far as the mechanics of breathing is concerned. III. DYNAMIC ANALYSIS OF THE MODEL The major difficulty in analysing the dynamic behaviour of the model lies in the fact that information on respiratory muscle pressure is still not experimentally available in terms of the magnitude and its time course pattern. Therefore, in the following analysis, the pattern of the alveolar pressure as shown in Figure 6, was assumed and used as the driving force does not affect the flow rate once it exceeds Palv’. Figure 7 shows the expired volume, flow rate, and applied alveolar pressure on the ordinate and time in seconds on the abscissa. It clearly demonstrates that the flow reaches Qmax at the point as indicated by the arrow in the figure and thereafter decreases despite further increase in the driving pressure. Figure 7A shows the volume and flow patterns obtained from the model, assuming an obstructed state. It may be seen that narrowing of the airway occurs in an earlier stage of expiration and at a higher lung volume than in the normal state. In the model analysis, it is possible to perform some studies which are difficult to do under actual experimental conditions. For instance, Figure 8 is a plot of the alveolar pressure and the lung volume at a constant flow rate. If a subject starts expiration with a constant flow rate, he/she can expire with this flow until the inflexion point in the figure is reached. Beyond this point, he/she cannot continue to expire with this flow rate even when the alveolar pressure rises to almost infinite values. Consequently, the flow must

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across the airway. As soon as the airway narrows, an opposing force to reopen the airway works the narrowed locus, and these two forces are balanced with negative feed back processes. This effects results in fixation of the transmural pressure at Ptm’.

[cmH2O]

[cmH2O]

[ ]

[l]

REFERENCES

[ ]

[l]

1. 2.

Fig. 8. Iso-flow - volume - pressure curves at different constant flow rates. A - normal, B - obstructed 3.

be reduced. Therefore, the line connecting all inflexion points (dotted line in the figure) represents the maximal effective alveolar pressure generated by the respiratory muscles at different lung volumes. IV. CONCLUSIONS In conclusion, most experimental observations on the pressure-flow-volume relationships of the lung so far reported can be explained by introducing the simple assumption that the resistance to the gas flow somewhere in the airway increases as a function of the transmural pressure

4.

Bouhuys A., Jonson B.: Alveolar pressure, airflow rate and lung inflation in man . J. Appl. Physiol. 22, 1967, 1086-1100 Fry D.L., Hyatt R.E.: Pulmonary mechanics. A unified analysis of the relationship between pressure, volume and gas flow in the lungs of normal and diseased human subjects. Amer. J. Med., 29, 1960, 672689. Fry D.L.: Theoretical considerations of the bronchial pressure-flowvolume relationships with particular reference to the maximum expiratory flow volume curve. Phys. Med. Biol ., 3, 1985, 174-195 Pride N.B., Permutt S., Riley R.L., Bromberger-Barnea B.: Determinants of maximum expiratory flow from the lungs. J.Appl.Physiol. 32, 1976, 646-662

Author: Institute: Street: City: Country: Email:

Bozena Kuraszkiewicz of Biocybernetics and Biomedical Engineering Trojdena 4 02-109 Warsaw Poland [email protected]

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Acetabular forces and contact stresses in active abduction rehabilitation H. Debevec1, A. Kristan2, B. Mavcic1, M. Cimerman2, M. Tonin2, V. Kralj-Iglic3, and M. Daniel1,4 1

Laboratory of Physics, Faculty of Electrical Engineering, University of Ljubljana, Slovenia 2 Department of Traumatology, University Medical Center Ljubljana, Slovenia 3 Laboratory of Clinical Biophysics, Faculty of Medicine, University of Ljubljana, Slovenia 4 Laboratory of Biomechanics, Faculty of Mechanical Engineering, Czech Technical University in Prague, Czech Republic Abstract— Operative fixation of fragments in acetabular fracture treatment is not strong enough to allow weight bearing before the bone is healed. In some patients even passive or active non-weight-bearing exercises could lead to dislocation of fragments and posttraumatic osteoarthritis. Therefore, early rehabilitation should avoid loading the acetabulum in the regions of fracture lines. The aim of the paper is to estimate acetabular loading in non-weight-bearing upright, supine and side-lying leg abduction. Three-dimensional mathematical models of the hip joint reaction force and the contact hip stress were used to simulate active exercises in different body positions. The absolute values of the hip joint reaction force and the peak contact hip stress are the highest in unsupported supine abduction (1.3 MPa) and in side-lying abduction (1.2 MPa), lower in upright abduction (0.5 MPa) and the lowest in supported supine abduction (0.2 MPa). The results are in agreement with the clinical guidelines as they indicate that upright abduction should be commenced first. Keywords— acetabular fracture, biomechanics, hip contact stress, rehabilitation.

I. INTRODUCTION Acetabular fractures are produced by high energy injuries that often cause dislocation of the fragments with gaps and steps [1]. The goal of operative treatment of such fractures is to restore acetabular anatomy with perfect fragment reduction and stable fixation in order to enable early joint movement [2],[3]. The fixation of the fragments is not strong enough to allow weight bearing before the bone is healed [4],[5] and in some patients even physical therapy with initial passive motion and continued active exercises without weight bearing could lead to dislocation of fragments and early posttraumatic osteoarthritis [2]. Early physical therapy of patients with acetabular fractures therefore requires careful selection of exercises in order to prevent excessive loading of the injured acetabular region. Current guidelines for nonoperative management of acetabular fractures and postoperative management of surgical procedures in the acetabular region recommend initial bed rest followed by passive motion in the hip joint. Initial active non-weight-bearing exercises commence a few days after surgery and include active flexion, extension and abduction

in the hip in the upright position. The same set of exercises in supine or side-lying abduction is usually postponed until 5-14 days postoperatively. Partial weight-bearing with stepwise progression usually starts 6 weeks postoperatively and full weight bearing is eventually allowed at 10 weeks [6]. Recently, interesting information was obtained by direct measurements of acetabular contact pressures during rehabilitation exercises in subject with pressure-instrumented partial endoprostheses where it was found that acetabular pressures may not follow the predicted rank order corresponding to the commonly prescribed temporal order of rehabilitation activities [7],[8]. Due to technical complexity and invasiveness of direct contact stress distribution measurement, various mathematical models for calculation of the hip joint loading force and contact stress distribution in the hip joint have been proposed [9]-[16]. Recently, a mathematical model has been developed that enables computation of the contact stress distribution at any given position of acetabulum and also allows simulation of different body positions and variations in pelvic morphology [10]-[12]. The aim of the paper is to compare acetabular loading in non-weight-bearing upright, supine and side-lying leg abduction by using a muscle model for computation of the hip joint reaction force and a previously developed mathematical model of contact hip stress distribution. With this knowledge the range of motion and body position during active exercises can be suggested that would prevent excessive loading of particular acetabular regions and displacement of fracture fragments. II. METHODS Biomechanical estimation of the hip joint loading was based on a mathematical model for computation of the hip joint reaction force and a previously developed model for computation of the contact stress distribution in the hip articular surface. The model for force assumes that the abduction exercise is performed slowly, i.e. the dynamic effects related to motion can be neglected and therefore the static calculation for given position of the leg is considered.

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Table 1 Muscles included in the musculoskeletal model of the hip joint No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Muscle adductor brevis

No. 15

Muscle. gluteus minimus 3

adductor longus adductor magnus 1 adductor magnus 2 adductor magnus 3 gemelli inf. et sup. gluteus maximus 1

16 17 18 19 20 21

iliacus pectineus piriformis psoas quadratus femoris biceps femoris long

gluteus maximus 2 gluteus maximus 3 gluteus medius 1

22 23

gracilis sartorius semimebranosus

gluteus medius 2 gluteus medius 3 gluteus minimus 1 gluteus minimus 2

24 25 26

semitendinosus tensor fascie latae

27

rectus femoris

In computation of the hip joint reaction force (R), the equilibrium equations of forces and torques acting on the lower leg are solved. The body weight is taken to be 800 N and the weight of the leg is taken to be 0.161 of the body weight [10]. The musculoskeletal geometry defining positions of proximal and distal muscle attachment points in neutral position and cross-sectional areas of the muscles is based on the work of Delp et al. [17]. Muscles attached over a large area are divided into separate units. Hence, the model includes 27 effectively active muscles of the hip (Tab. 1). Muscle activity required to maintain equilibrium in a given position of body is computed using the method of inverse dynamic optimization [18] proposed by Crowninshield et al. [19]. Each specific type of abduction exercise was modeled by rotation of the leg in the frontal plane of the body around the center of the femoral head (Fig. 2) while the pelvis was taken to be fixed in a laboratory coordinate system. The position of the leg during abduction exercise was defined by the abduction angle (Fig. 2a).. Supine abduction of unsupported straight leg without touching the ground and supine abduction of straight leg with 80% of the weight of the leg support were analyzed separately. The supporting force of the ground was considered to act in the center of the gravity of the leg. The distribution of the hip contact stress for given position of the leg was computed using the computer program HIPSTRESS [10]-[12]. Radius of acetabular surface was taken to be 25 mm, the lateral inclination and anteversion of acetabulum was taken to be 30 and 15 degrees, respectively.

Fig. 1 Body position during standing abduction (a), sidelying abduction (b), supported supine abduction (c) and unsupported supine abduction (d). III. RESULTS The magnitudes of the hip joint reaction force R and the peak contact stress pmax during abduction exercises in different body positions are shown in Fig. 2a and Fig. 2b respectively. The loading of the acetabulum is the lowest in supported supine abduction and the highest in unsupported supine abduction. The force R as well as the peak contact stress pmax increase with the angle of abduction during standing and decrease during side-lying. When the supine abduction is performed, the hip joint reaction force R and the peak contact hip stress pmax vary only a little.

Fig. 2 Magnitude of hip joint reaction force R (a) and the peak contact stress pmax (b) during abduction exercises

IV. DISCUSSION We have found that in the neutral leg position the hip joint reaction force is high for side-lying or unsupported supine body position and low for upright standing. This can

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be explained by considering the equilibrium of the moments of the gravitational and muscular forces with respect to the center of rotation of the hip joint in different body positions. In standing and side-lying abduction the equilibrium is maintained by the activity of abductors. In side-lying abduction higher abductor force is required to compensate the weight of the lower leg than in the standing abduction because of larger lever arm of the weight of the lower leg in former case. After increasing the angle of abduction in upright standing, the center of the gravity of the lower leg moves laterally, which further increases the gravitational moment. Hence the counteracting muscle activity as well as the hip joint load must be increased. On the other hand, abduction of the lower leg in the side-lying exercise decreases the gravitational moment of the lower leg with respect to the hip and the hip load is decreased. However, in the unsupported supine abduction, the leg has a tendency to extend and hence the activity of flexors is required. In the supine abduction flexors that are required to maintain this posture have smaller moment arms and thus demand high flexor forces. Therefore the hip joint reaction force magnitude in unsupported supine position is considerably higher when compared to other body positions, however, ground support of the leg can proportionally reduce its magnitude. The course of pmax follows the course of the hip joint reaction force for upright and side-lying abduction (Fig. 2b). In contrast, abduction of the leg does not considerable change the peak contact hip stress in supine abduction and pmax remains almost constant throughout the abduction arch both with unsupported and supported leg. The average loading of the hip joint is the lowest in 80% supported supine abduction and the highest in unsupported supine abduction. Computed values of hip joint reaction force and peak contact hip stress reported in our paper are of the same order of magnitude as the ones performed in non-weightbearing exercises measured in vivo [7],[8]. Peak stress in direct measurements was also located in the posteriorsuperior acetabular quadrant, which is the case also in our study. Direct measurements of peak contact stress in supine abduction were found to be 2.8 MPa and 3.8 MPa in vivo [7],[8] versus 1.3 MPa in our study. The reports do not specifically mention the amount of vertical leg support in supine adduction, but considering the fast velocities it could be inferred that the abduction was unsupported. Contrary to our findings and to clinical guidelines, the only in vivo study that compared abduction in different body positions has found quite a different rank order of the peak contact hip stress values with 8.9 MPa in standing hip abduction, 5.6 MPa in side-lying hip abduction and 2.8 in supine hip abduction [7]. It should be noted, however, that these in vivo measurements were performed with angular velocities

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above 30°/s and therefore also include the dynamic component of loading. Furthermore, a change from a side-lying body position to an upright position considerably reduces the moment arm of the leg weight but it does not substantially influence the moment arms of individual muscles. In static conditions, a reduced moment arm of the leg weight in the upright position reduces the calculated muscle forces and consecutively lowers the hip load, as shown in Fig. 2. However, in dynamic motion, a smaller moment arm of the leg weight in the upright position would facilitate an initial acceleration of the leg that later requires higher muscle strength to stop the movement at maximal abduction. Comparison between dynamic measurements and static computations therefore indicates that at very slow motion the upright abduction causes lower contact hip stresses than sidelying abduction, but this may be reversed in maximum abduction at high angular velocity. One of the reasons for performing only high speed measurements may have been the measurement error of approximately 0.2 MPa that was not accurate enough for slow non-weight bearing measurements with magnitudes below 1 MPa. When direct measurements of contact hip stress were compared with simultaneous hip stress estimations through kinematics measurements, it was found that direct measurements of the same activities yield considerably higher contact stress than inverse Newtonian analyses [20]. This effect has been attributed to cocontraction of muscles that is especially apparent in relatively slow, controlled movements [20] and this may to some extent explain the discrepancy between our results and results obtained by direct dynamic measurements. V. CONCLUSION We conclude that absolute values of the hip joint reaction force and the peak contact hip stress are highest in unsupported supine abduction, slightly lower in side-lying abduction and lowest in upright abduction. Our results are in agreement with the clinical guidelines as they indicate that upright abduction should be commenced first [6]. Supine abduction in initial rehabilitation phases should be recommended with ground support (on the bed) without excessive vertical leg lifting. Our results complement the results of direct measurements of stress during exercises and the experience – based exercise protocols in elucidating the mechanical impacts on the rehabilitation.

ACKNOWLEGMENT The research is supported by the Czech Ministry of Education project No. MSM 6840770012 and by the Slovenian ARRS Projects No. P2-232J3-619 an BI-CZ/07-08-006 and BI-S/05-07-002.

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REFERENCES 1.

S. A. Olson , B. K. Bay, and A. Hamel (1997) Biomechanics of the hip joint and effects of fracture of the acetabulum, Clin Orthop, vol 339, pp. 92-104. 2. E. Letournel, and R. Judet, Fracture of the acetabulum. New York: Springer; 1993. 3. M. Tile, “Fractures of the acetabulum”, in The Rational of Operative Fracture Care, 2nd ed., J. Schatzker and M. Tile, Eds., Berlin: Springer 1996, pp. 271-324. 4. S. A. Olson, B. K. Bay, M. W. Chapman, and N. A. Sharkey (1995) Biomechanical consequences of fracture and repair of the posterior wall of the acetabulum, J Bone Joint Surg (Am), vol 77, pp. 11841192. 5. J. A. Goulet, J. P. Rouleau, D. J. Mason, and S. A, Goldstein, (1994) Comminuted fracture of the posterior wall of the acetabulum. A biomechanical evaluation of fixation methods.J Bone Joint Surg (Am), vol.76, pp. 1457-1463. 6. S. F. Maurer, B. Mutter, K. Weise, H. Belzl (1997) Rehabilitation nach Hüftgelenkfrakturen, Orthopäde, vol. 6, pp. 368–374. 7. S. J. Tackson, D. E. Krebs, and B. A. Harris,. (1997) Acetabular pressures during hip arthritis exercises,” Arthritis Care Res, vol 10, pp. 308-319 8. D. L. Givens-Heiss, D. E. Krebs, P. O. Riley, et al. (1997) In vivo acetabular contact pressures during rehabilitation, Part I: Acute phase, Phys Ther, vol 72, pp. 691-699, 1992. 9. R. A. Brand (2005 )Joint contact stress: a reasonable surrogate for biological processes?, Iowa Orthop J, vol. 25, pp. 82-94. 10. A. Iglič, V. Kralj-Iglič, M. Daniel, and A. Maček-Lebar, (2005) Computer determination of contact stress distribution and the size of the weight-bearing area in the human hip joint, Comput Methods Biomech Biomed Engin, vol 5, pp.185-192. 11. M. Ipavec, R. A. Brand, D. R. Pedersen, et al. (1999) Mathematical modelling of stress in the hip during gait, J Biomech, vol 32, pp. 1229-1235. 12. B. Mavčič, B. Pompe, M. Daniel, et al.(2002) Mathematical estimation of stress distribution in normal and dysplastic human hip, J Orthop Res, vol 20, pp. 1025-1030A.

13. R.A. Brand, A. Iglič, and V. Kralj-Iglič, (2001) Contact stresses in human hip: implications for disease and treatment, Hip Int. vol. 11, pp.117-126. 14. E. Genda, N. Konishi, Y. Hasegawa, and T. Miura (1995), A computer simulation study of normal and abnormal hip joint contact pressure,” Arch Orthop Trauma Surg, vol 114, pp. 202-206. 15. H. Legal, “Introduction to the biomechanics of the hip”. in Congenital dysplasia and dyslocation of the hip, D. Tönis Ed., Berlin: SpringerVerlag, 1987, pp. 26-57. 16. R. A. Brand, D. R. Pedersen, D. T.Davy, et al. “Comparison of hip force calculations and measurements in the same patient,” J Arthroplasty., vol. 9, pp. 45-51, 1994. 17. S. L. Delp, P. Loan, M. G.Hoy, et al. (1990) An interactive graphicsbased model of the lower extremity to study orthopaedic surgical procedures, IEEE Trans Biomed Eng, vol 37, pp. 757-767. 18. D. Tsirakos, V. Baltzopoulos, and R. Bralett. (1997) Inverse optimization: functional and physiological considerations related to the force sharing problem, Crit Rev Biomed Eng, vol. 25, pp. 371-407. 19. R. D. Crownishield, and R. A. Brand (1981), “A physiologically based criterion for muscle force prediction and locomotion,” J Biomech, vol 14, pp. 793-801. 20. S. Park, D. Krebs, and R. Mann, “Hip muscle co-contraction: evidence from concurrent in vivo pressure measurement and force estimation,” Gait Posture.vol 10, pp. 211-222, 1999. Author: Dr. Matej DANIEL Institute: Laboratory of Biomechanics, Department of Mechanics, Biomechanics and Mechatronics, Faculty of Mechanical Engineering, Czech Technical University in PRague Street: Technicka 4 City: Prague Country: Czech Republic Email: [email protected]

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Experimental verification of the calculated dose for Stereotactic Radiosurgery with specially designed white polystyrene phantom B. Casar, A. Sarvari Institute of Oncology Ljubljana/Department of Radiophysics, Ljubljana, Slovenia Abstract— Accuracy in the dose delivery in the Stereotactic Radiosurgery is one of the most important components in this sophisticated radiotherapy treatment of benign and malignant intracranial diseases. In the present study, we carried out the measurements with small volume cylindrical ionization chamber PTW 31006 (PinPoint), together with specially designed and elaborated bullet-shaped white polystyrene phantom in order to verify the dose calculation by the commercially available 3D treatment planning system BrainScan from BrainLab company. Comparison of the doses was done in four simulated simple treatments, applying non-coplanar circular arc technique with tertiary conical collimators on linear accelerator Varian Clinac 2100 C/D with high energy photon beams of 6 MV. We found systematic differences in all four cases. The differences were found to range from 2.4% to 3.9% - the measured doses were always higher than the calculated ones. Although the results of our study could confirm the accuracy of the treatment planning dose calculations, as the differences lie within the recommended 5% value of the International Commission on Radiation Units and Measurements (ICRU), it is advisable to investigate further the origin of these, most probably systematic errors. However, the use of small volume ionization chamber and of homemade polystyrene phantom for dosimetrical verifications, has proved to be appropriate. Keywords— stereotactic radiosurgery, conical collimators, linear accelerator, dosimetry

I. INTRODUCTION Stereotactic radiosurgery (SRS) is a special focal radiotherapy technique for the treatment of small malignant and benign intracranial and lately also extracranial lesions. Two main components, a dosimetrical and a geometrical one, are important in allowing a successful delivery of the prescribed dose to the preselected stereotactically localized lesion. The requirements for dosimetrical accuracy follow the specifications of the International Commission on Radiation Units and Measurements (ICRU) [1], where an overall accuracy in the dose delivery of ± 5% is recommended, which is similar to that in standard radiotherapy. The requirements for geometrical accuracy are more stringent than in standard radiotherapy because SRS is commonly applied in the treatment of small lesions in the proximity of vital organs and critical structures that are at risk. The positional accuracy of dose delivery should be within ± 1 mm.

The name stereotactic radiosurgery was given by Swedish neurosurgeon Leksell in the early 1950 s when he introduced single session treatments of intracranial targets using 200 kVp x-ray unit [2, 3]. Even though the number of focused beams was large, they were not penetrating enough to deliver a satisfactorily concentrated dose to the target volume. These treatment modes were soon given up. In 1968, a prototype of a specially designed radiosurgical unit based on 60Co gamma rays was introduced into clinical practice [4]. Also this unit was originally developed by Leksell. Due to a higher energy of 60Co gamma rays (E=1.25 MeV), the beams were penetrating enough to deliver a satisfactorily concentrated dose to the target volume. A modified unit has been commercially available for a few decades under the name “Gamma knife”. In the 1980's several radiosurgical techniques were developed, all having an isocentric linear accelerator as the source of radiation [5, 6, 7, 8, 9]. Although also other radiosurgical techniques were developed in the last decades (treatments with protons, light ions, etc.), we will not describe all of them here. At the Institute of Oncology in Ljubljana, SRS technique with linear accelerator was introduced into clinical practice in 1999. The majority of the equipment for linear accelerator Philips SL–75/5, producing 5 MV photon beams was designed and assembled by B. Casar and colleagues [10]. Due to specific circumstances, this treatment modality was soon given up, therefore, only one patient was treated, yet this one very successfully. After the purchase of commercially available radiosurgical equipment, this technique regained its appreciation and was reintroduced. In this study, we limited our research intentions to the verification of accuracy of the delivered dose in a few simple treatment plans. II. MATERIALS AND METHODS A. 3D SRS treatment planning For the purpose of dose verification, we designed and elaborated a special bullet-shaped white polystyrene phantom in order to simulate a real clinical situation. A phantom consists of a hemisphere with the diameter of 16 cm and a cylinder with the diameter of 16 cm and the height of 8 cm. Inside the hemisphere, there is a cylindrical hollow, with the diameter of 2 cm, in which a rod insert for

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a chosen ionization chamber fits exactly. In the inserted rod a cavity is drilled so that the chamber exactly fits in. For the dose verification we selected waterproof PTW 31006 PinPoint chamber with an active volume of 0.015 cm3. Small chamber dimensions ensure that correct measurements are obtained also in case of measuring the doses for small treatment volumes. The phantom was fixed with 4 carbon pins in the stereotactic head ring which is part of our SRS system manufactured by BrainLab company. Onto the head ring, we attached a localization box which was used for the determination of local coordinate system using Z-shaped fiducial rods (Fig. 1). In order to acquire a set of 3D images of our phantom, the assembled set, together with PinPoint chamber, was scanned on a Philips MX8000D spiral CT and images were then exported to the 3D treatment planning system BrainScan (company BrainLab). The slice thickness was 3.2 mm and the slice increment 1.6 mm, which allowed good spatial resolution. Four simple SRS simulated treatment plans for our polystyrene phantom were made for the Varian 2100 C/D linear accelerator which will be clinically used in later treatments. For all plans, we used the technique with which we irradiated our phantom with 3 non-coplanar circular arcs. Circular conical collimators were used as beam shaping devices – these collimators can be easily attached onto the head of the linear accelerator. We used collimators with the nominal field diameters of 15.0 mm, 17.5 mm, 20.0 mm and 22.5 mm. Field diameters are defined in the isocenter of linear accelerator at the SAD distance of 100 cm from the source of radiation.

B. Casar, A. Sarvari

Fig. 2. Dose distribution in a phantom, calculated with the 3D planning system BrainScan. Isocenter was put in the middle of the active volume of the PinPoint ionization chamber. In this figure, the distribution of the dose in 3 orthogonal planes through the isocenter is shown. We chose a simple spherical object as target volume. The isocenter was put exactly in the middle of the active volume of the ionization chamber to minimize possible biases in dose measurements. For one of the plans, the dose distribution in three orthogonal planes through the isocenter is presented in figure 2 (Fig. 2). Important data of all treatment plans and corresponding setup of linear accelerator are shown in the table 1. Table 1 Data for four treatment plans using various conical collimators. Plans were calculated for 6MV high energy photon beams on Varian clinic 2100 C/D linear accelerator. Calculations were performed with 3D treatment planning system BrainScan. Collimator diameter [mm]

Table angle [°]

Gantry start [°]

Gantry stop [°]

MU

Dose in isocenter [Gy]

15.0

45 0 315 45 0 315 45 0 315 45 0 315

75 330 225 75 330 225 75 330 225 75 330 225

135 30 285 135 30 285 135 30 285 135 30 285

734 701 704 718 682 686 709 675 678 691 662 665

15.0

17.5

20.0

22.5

Fig. 1. SRS system together with the phantom fixed with pins in the head ring. The PinPoint chamber is inserted into the phantom. Tertiary circular conical collimator is attached onto the head of linear accelerator.

15.0

15.0

15.0

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B. Cross calibration of PinPoint ionization chamber For dose (charge) measurements, we need a properly calibrated ionization chamber. Since the calibration factor in terms of Dose to Water – ND,w,Qo,P - for reference beam quality 60Co for our PinPoint chamber was not determined, we had to obtain it by cross calibration with the ionization chamber of known calibration factor. The cross calibration was performed on 60Co treatment unit Theratron 780C (company Nordion) using the calibrated PTW 30013 (#1669) Farmer type ionization chamber. The charge was measured with PTW Unidos electrometer. For each chamber, five measurements in water phantom were made under the following conditions: SSD (source to surface distance) = 80 cm, radiation field size at the water surface = 10 x 10 cm2, gantry and collimator were set to 0°, and the irradiation time was 1.00 minute. The central axes of the chambers were at the depth of 10 cm in the water phantom. During the measurements, the reference voltage on chamber electrodes was +400 V for both chambers. Prior to the measurements each chamber was left in water for 15 minutes for temperature equilibration and water temperature and air pressure were controlled with digital thermometer and barometer. Both chambers were waterproof and vented through the connecting cables. The calibration factor ND,w,Qo,P for PinPoint chamber for reference beam quality Q0 in 60Co beam was determined according to IAEA TRS–398 dosimetry protocol [11] from the equation MQ,P ND,w,Qo,P = MQ,F ND,w,Qo,F

(1)

where MQ,F is the average of five readings of collected charge for the reference Farmer chamber, and MQ,P is the average collected charge for PinPoint chamber, both readings corrected for temperature and pressure. ND,w,Qo,F is the calibration factor for Farmer chamber in the reference beam quality Q0 of 60Co beam.

Fig. 3. Setup for one of the arc beam with the table rotation and gantry start angle position.

For each arc, we measured the collected charge with PTW Unidos electrometer and then calculated the absorbed dose Dw,Q (zref) at the reference point zref of the chamber according to the dosimetry protocol IAEA TRS-398 [11] Dw,Q (zref) = MQ ND,w,Qo,P kQ,Qo

where MQ is the sum of electrometer readings for one session (3 arcs), corrected for temperature and pressure, ND,w,Qo,P is the obtained calibration factor for PinPoint chamber in 60Co beam (reference beam quality Q0), and kQ,Qo is the chamber specific factor correcting for the difference between the reference beam quality Q0 and the quality Q of the high energy photon beams of 6 MV which were used in our study. Factor kQ,Qo was calculated from the updated version of IAEA TRS–398 protocol and was found to be 0.993. III. RESULTS

C. Verification of calculated dose The calculated dose in the isocenter was checked for four treatment plans using PinPoint chamber. Polystyrene phantom with the inserted PinPoint chamber, head ring and localization box were fixed onto the linear accelerator table. Using the system of 3 orthogonal lasers that intersected at the same point, we located the chamber reference point, which is in the middle of the chamber’s active volume, to the isocenter of linear accelerator. The calculated data (irradiation times for each arc and other geometrical parameters) were transferred to the linear accelerator console and the irradiation was performed according to the planned data (Fig. 3).

(2)

Two independent cross calibrations were performed. The calibration factors were calculated using the equation 1. The results of calibrations are shown in Table 2. Table 2 Two independent measurement results for the determination of calibration factor for PinPoint chamber ND,W,Q0,P in terms of Dose to Water MQ,P1 [nC]

MQ,F1 [nC]

325.2 14.683 ND,W,Q0,P1 = 2.423 mGy/nC ND,W,Q0,P = 2.427 mGy/nC

MQ,P2 [nC]

MQ,F2 [nC]

323.9 14.676 ND,W,Q0,P2 = 2.431 mGy/nC

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The average of two calculated calibration factors from two independent cross calibrations was regarded as the valid calibration factor for PinPoint chamber, thus, the calibration factor for PinPoint chamber was found to be ND,w,Qo,P = 2.427 mGy/nC. The dose measurement results for all four treatment plans are presented in Table 3. The doses were calculated according to the equation 2 where the electrometer readings were corrected for the influence of temperature and pressure.

erance limit according to the recommendation of ICRU (5%). It was shown that the choice of small volume PinPoint detector for such measurements was correct and that the polystyrene phantom was proved to be an easy and acceptable solution for quality assurance and quality control purposes of such and similar dosimetrical tests. Further investigation of the observed differences is needed.

Table 3 Results of comparison between the calculated and measured doses

Present study was partly done in the framework of research program “Development and Evaluation of New Approaches to Cancer Treatment” (P3-0003(D)), supported by the Slovenian Research Agency (ARRS).

for treatment plans using four different conical collimators.The doses were calculated and measured in the isocenter of linear accelerator. The last column represents ratios between the measured and calculated doses. Cell diameter [mm]

Dcalc [Gy]

Dmeas [Gy]

Dmeas/Dcalc

15.0 17.5 20.0 22.5

15.0 15.0 15.0 15.0

15.36 15.44 15.59 15.39

1.024 1.029 1.039 1.026

IV. DISCUSSION Comparison of the results showed that the measured doses were always higher than the calculated ones. For the selected conical collimators, the differences between the calculated and measured doses varied from 2.4% to 3.9%. The average value of our set of measurements was 15.45 Gy, giving the average difference of 3.0% between the measured and calculated doses and standard deviation of the mean value 0.10 Gy (coverage factor k= 2). Although these differences lie within the ICRU recommendations of 5%, a challenge to investigate the origin(s) of these differences has been posed, especially because their tendency is in the same direction and it is highly probable, that the found differences could reveal a systematic error. There are many possible reasons for the dose differences and they are to be verified in further studies: error in cross calibration, errors in the treatment planning algorithm, errors in the import of the basic dosimetrical data into the treatment planning system, error in path length correction for the phantom material and probably a few more.

ACKNOWLEDGEMENT

REFERENCES 1.

International Commission on Radiation Units and Measurements (ICRU). (1976) ICRU Report 24. Determination of Absorbed Dose in a Patient Irradiated by Beams of X or Gamma Rays in Radiotherapy Procedures 2. Leksell L. (1949) A stereotactic apparatus for intracerebral surgery. Acta Chir. Scand. 99:229-233 3. Leksell L. (1951) The Stereotaxis method and radiosurgery of the brain. Acta Chir. Scand. 102:316-319 4. Leksell L. (1968) Cerebral radiosurgery I.Gamma thalamotomy in two cases of intractable pain. Acta Chir. Scand. 134:585-595 5. Betti OO, Derechinsky VE. (1984) Hyperselective encephalic irradiation with a linear accelerator. Acta Neurochir.Suppl. 33:385-390 6. Colombo F, Benedetti A, Pozza F, et al. (1985) External stereotactic irradiation by linear accelerator. Neurosurgery 16:154-160 7. Hartmann GH, Schlegel W, Sturm V, et al. (1985) Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. Int. J. Radiation Oncology Biol. Phys. 11:1185-1192 8. Houdek PV, Fayos JV, Van Buren JM, et al. (1985) Stereotactic radiotherapy technique for small intracranial lesions. Med. Phys. 12:469-479 9. Podgorsak EB, Olivier A, Pla M, et al. (1988) Dynamic stereotactic radiosurgery. Int. J. Radiation Oncology Biol.Phys. 14:115-126 10. Casar B. (1998) Tertiary collimator system for stereotactic radiosurgery with linear accelerator. Radiology and Oncology 32(1):125-128 11. International Atomic Energy Agency (IAEA) (2000) Absorbed Dose Determination in External Beam Radiotherapy. An International Code of Practice for Dosimetry Based on Standards of Absorbed Dose to Water, Technical Report Series no. 398, Vienna. IAEA Author: Bozidar Casar

V. CONCLUSION Although the measurements do not confirm the calculated doses within our expectations (2%), they confirm the treatment planning calculations of the doses within the tol-

Institute: Street: City: Country: Email:

Institute of Oncology Ljubljana Zaloska 2 Ljubljana Slovenia [email protected]

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Implantable brain microcooler for the closed-loop system of epileptic seizure prevention I. Osorio1, G. Kochemasov2, V. Baranov2, V. Eroshenko2, T. Lyubynskaya2, N. Gopalsami3 1

Flint Hills Scientific, Lawrence, KS and University of Kansas Medical Center, Kansas City, KS, USA 2 BioFil (Biophysical Laboratory) and Russian Federal Nuclear Center-VNIIEF, Sarov, Russia 3 Argonne National Laboratory, Argonne, IL, USA

Abstract– A method of thermal suppression of abnormal brain activity observed in epileptic patients during preictal stage was considered for seizure blockage. The development of an implantable brain microcooler as a part of a closed-loop epileptic seizure prevention system is reported. An array of 7 needle-like probes of the diameter ~1 mm and length ~2 cm provides cooling of 1 cubic inch of brain tissue from ~370C to ~160C in ~30 sec. Convective method of heat exchange with tube in a tube design was adopted. Two coaxial steel tubes formed channels for the direct and reverse flows of precooled water. Theoretical studies and numerical modeling based on Pennes' equation were performed to investigate the process of brain tissue cooling. Experimental tests demonstrated good agreement with calculations. A closed cycle cooling system with a peristaltic pump and thermoelectric cooling device is being prepared for animal tests. As an additional option a single-probe microcooler of the probe length ~5 cm was developed, fabricated, and tested for cooling of deep brain areas such as hippocampus. Keywords– epilepsy, seizure blockage, closed-loop system, implant, brain microcooler.

I. INTRODUCTION Epilepsy is a neurophysiological disorder and its consequences are severe resulting in repetitive seizures accompanied by disturbance in brain electrical activity, convulsions, uncontrolled changes in behavior, loss of consciousness and at worst – death. Statistics over industrialized counties gives 40 million people suffering from epilepsy in North America and Europe. The rate for underdeveloped countries is believed to be an order higher. Most people suffering from epilepsy are of normal intellect and could be valuable members of society, but permanent threat of seizure puts severe restrictions on their way of living and work. Only part of them can be returned to normal life by means of chemical therapy. As an alternative to drug treatment, brain stimulation systems are under development over the world. The most advanced “closed-loop” technologies combine seizure prediction, stimulation and control units into automated autonomic seizure prevention system [1, 2]. The physical principles of epileptic seizure detection and stimulation may

vary, but the most widespread is the electrical one [3]. An alternative approach suggested in the literature is temperature control and brain cooling as a possible and effective way of epilepsy treatment [4]. Though the mechanism of seizure development is not well understood, some authors believe that in the preictal state neural electrical activity become more ordered and correlated compared to that of normal state [4]. Brain cooling results in reduction of synaptic electrical conductivity thus decreasing the inter-neural coupling. It was proved in clinical studies that the local temperature in the vicinity of the epilepsy region increased by ~1.5 K about 30 sec before the seizure onset [5]. The device described here is intended for thermal suppression of abnormal neural activity based on sensing local temperature changes in the brain. The cooling device will be integrated with an implantable SAW-sensor for temperature monitoring [6] and a telemetry controlling system with signal processing, seizure prediction, decision-making, and triggering functions. The technical requirements on brain microcooler development were to cool 1 cubic inch of brain tissue from ~370C to ~160C in ~30 sec. In animal tests it was proven that the lower limit of 160C is sufficient for the idea to work. On the other hand, the temperature of the implantable part of the microcooler must not be lower than 40C to avoid irreversible damage of brain tissue. II. THEORETICAL APPROACH TO MICROCOOLER DEVELOPMENT

An estimate of thermal wave penetration depth as a function of time t is given by: Ld = χ ⋅ t

where, χ is thermal conductivity. Assuming χ = 0.0014 cm2/sec and t = 30 s, one obtains Ld ∼ 2 mm. It means that in order to cool quite a large brain area a multiprobe construction with probe-to-probe distances ~ 2⋅Ld must be applied.

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For numerical simulation of heat transmission process in the brain-like tissue, a suite of computer programs was created providing calculations in 1D-, 2D- and 3Dapproaches. The cooling process was described by Pennes' equation [7]: ∂T = ∇(λ ⋅ ∇T ) + μ ⋅ (Ta − T ) + ν c⋅ρ ⋅ ∂t

The physical parameters used in the calculations are given in Table 1. Table 1. Physical parameters used in the calculations Parameter Heat capacity Density

Meaning c = 3.6 J/g/K

Thermal conductivity Exchange rate with arterial blood thermal pool

ρ = 1 g/cc λ = 0.005 W/cm/K μ = 0.029 W/cc/K

Arterial blood temperature

Ta = 37°C

Metabolic heat production rate

ν = 0.025 W/cc

Initial temperature of the tissue

T0 = 37°C

To provide constant temperature on the probe surface the heat obtained from the surrounding tissue must be constantly removed. For this purpose three possible operation principles were considered: passive heat removal using probe material with high thermal conductivity, evaporation cooling based on Joule-Thompson effect, and convective cooling by pumping of precooled water inside the probe. The third option was chosen for realization as the simplest and the most reliable. Two coaxial tubes provided channels for direct (the inner tube) and reverse (annular gap between tubes) liquid flows. The following considerations were taken into account for microcooler design development: • Thermal flux per probe and acceptable heating of cooling liquid determine required mass consumption: m ≥ Pth c ⋅ ΔT . For Pth = 0.5W, c = 4.2 J/g/K and ΔT = 3K mass consumption is m ≥ 0.04 g / sec •

δ

d

≤π ⋅

λl

cl ⋅ m

⋅L ,

where δ is the ring channel width and d is the probe diameter, λl – cooling liquid thermal conductivity, cl – cooling liquid heat capacity, dm/dt – liquid consumption, L – probe length. For d = 1 mm, λl = 0.0058

W/cm/K, cl = 4.2 J/g/K, dm/dt = 0.04 g/sec, and L = 2 cm one can obtain the ratio δ/d ≤ 0.2. III. 7-ELEMENT MICROCOOLER FABRICATION AND TESTS A 7-probe microcooler (Fig. 1) was fabricated and tested in the laboratory. Six probes are placed in the form of regular hexagon around the central 7th probe. Center-tocenter distance between the probes is 4.5 mm. Probe length is 2 cm. Each probe is made of a pair of syringe needles of the diameters 0.6 and 1.0 mm located concentrically. The distal end of the external pipe is soldered. The internal pipe is 2 mm shorter than the external one. Each probe is fed with cooled water through the internal pipe from the common collector. The layout of the cooling experiments is presented in Fig. 2.

Fig. 1 ImplanTable 7-probe convective brain microcooler. The precooled subsystem shown in the Fig. 2 with Pelltier element and peristaltic pump is intended for animal tests and at present is under development. In the laboratory tests the source of cooling was a perfusor with a syringe filled with icy water. Liquid mass consumption is 800 ml/h for the cooler as a whole or 0.0317 ml/sec per probe. Agar jelly was used as brain tissue surrogate in the laboratory experiments. The temporal behavior of temperature was measured by thermocouples placed into the flowing water at the microcooler input, output, and in agar jelly approximately in the center of one of the regular triangles formed by the probes. For future animal tests thin insulated copper wire was soldered to each probe to provide brain electrical signal measurements.

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IV. COMPARISON BETWEEN EXPERIMENTAL AND

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Direct modeling of the cooling process for the micro cooler is extremely difficult mainly because of short time of water staying in the probe. The diameter of internal channel is 0.35 mm; the internal and external diameters of the annular channel are 0.6 and 0.75 mm, respectively. So for the flow rates mentioned above, the estimated time of elementary volume being inside the probe is 0.16 sec. To make calculation of heat exchange between liquid flow and tube walls stable the step of integration must be at least by an order of magnitude smaller. Taking into account the fact that the task in general is 3-dimentional with total number of nodes up to ~106, one can see that the computation time is unreasonably large. So, a different approach was chosen. First, a 2D axially symmetric calculation was done for convective single probe put into cylindrical block of surrounding matter with adiabatic boundary conditions at the external surface. The input water temperature was assumed constant as used in the experiment. The goal of this step was to obtain the temperature of the probe surface as a function of longitudinal coordinate and time. These dependencies were used in 3D calculation as boundary conditions between the probes and the surrounding matter. The results of comparison of experimental and calculated temporal temperature behavior are given in Fig. 3. The graph Tin (blue curves) show the changes in water tempera-

8

1

10

9 2

15 10

Texp Tin

5

Tcalc 0 0

50

100

150

200

250

time, sec

Fig. 3 Comparison of experimental results and numerical modeling for 7element convective cooler. Tin – water temperature at the cooler input, Texp and Tcalc – the temperature resulted from experimental measurements and numerical modeling at the same point between probes. ture at the cooler input. The graph Texp (red curve) gives the temperature in agar jelly between the probes at the point most distant from the nearest three probes. The graph Tcalc (green curve) shows the results of numerical modeling at the same point as Texp. Generally, the agreement between the experimental and calculated curves is good. In the beginning of the measurements some amount of residual warm water in the system gave a slight rise in the input temperature as well as in the agar jelly temperature. Because of heat exchange of the precooling system with surrounding air, the input water temperature, after 100 seconds of measurement, increased causing difference between experimental and calculated temperature of ~1.50C toward the end of experiment. V. LONG SINGLE-PROBE MICROCOOLER DEVELOPMENT

3 4 7 6

T, 0 C

11

12

5

Fig. 2 Layout of the cooling experiments. 1 – peristaltic pump; 2 – thermoelectric unit; 3, 9 and 10 – heat exchanger radiator; 4 – micro cooler case; 5 –brain section under cooling; 6 – cooling probes; 7 – needle thermocouple; 8 – temperature indicator; 11 – power supply battery for thermoelectric unit; 12 – power supply unit for peristaltic pump.

In addition to the array probe, a ‘long’ single-probe microcooler was fabricated and tested in a similar way. It is intended as a prototype of the cooling device for deep area of the brain such as hippocampus. Apart from the number and the length of cooling probe the design of the singleprobe microcooler is similar to that of the 7-element one. The cooling probe is a tube in a tube with their external diameters 0.85 and 1.6 mm and length 50 mm. The inner tube is made of a 0.45 mm ID quartz capillary which helps decrease the heat flux through the sidewalls of the probe. A syringe needle of the internal diameter 1.1 mm served as the external tube. The capillary was glued with epoxy adhesive into the input collector and the external tube was glued into the bottom washer. To decrease the cold loss an additional isolating PVC covering was placed on the external tube. The length of the covering is 10 mm shorter than that of the external pipe. So the most intensive cooling is provided on

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the section of 10 mm from the probe tip. The tip is a passive thermoconductive cone of the length ~10 mm.

REFERENCES 1.

VI. CONCLUSIONS Based on the premise that local cooling can reduce synaptic electrical conductivity and in turn suppress the abnormal brain activity, an implantable brain microcooler has been developed, fabricated and tested in the laboratory. It is designed to cool a volume of ~1 cubic inch of brain matter from ~370C down to 160C in about 30 s. It is a part of an epilepsy prediction and control system comprised of a prediction sensor, the micro cooler, and a telemetry unit that starts the cooler based on the sensor reading. Theoretical study and numerical modeling were performed to investigate the brain tissue cooling process and offer a design solution for the microcooler. The experimental results of the microcooler in a brain surrogate are in good agreement with model and demonstrated that the device met the technical requirements. In addition, a single-probe microcooler of the probe length ~5 cm was developed, fabricated and tested for cooling deep brain regions such as hippocampus. Although the microcooler under development was meant to be a part of a closed-loop epilepsy seizure prevention system, it also could be engaged in an open-loop system as a less traumatic and risky alternative to drug and electrical stimulation. The cooling regime in this case is simpler than that of the closed loop autonomous system. Animal tests are supposed to be started soon by the industrial partner of the project Flint Hills Scientific.

ACKNOWLEDGMENT This work was supported by funding from IPP (Initiatives for Proliferation Prevention) Program of U.S. Department of Energy under the contract ANL-T2-214A.

2

3 4

5 6 7

8

Osorio I., Frei M., Manly F., et al. (2001) An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy, J Clin Neurophysiol. 18:533-544. Litt B., D’Alessandro M., Esteller R., et al. (2003) Translating seizure detection, prediction and brain stimulation into implantable devices for epilepsy, Proceedings of the 1st International IEEE EMBS Conference on Neural Engineering, Capri Island, Italy, 2003, pp 485-488. Osorio I., Frei M., Sunderam S., et al. (2005) Automated seizure abatement in humans using electrical stimulation, Ann Nurol. 57:258-268. Yang X.-F., Duffy D., Morley R., Rothman S. (2002) Neocortical seizure termination by focal cooling: temperature dependence and automated seizure detection. Epilepsia 43(3):240-245. Sackellares C., Iasemidis L., Shiau D., et al. (2000) Epilepsy – when chaos fails, In: Chaos in the brain, World Scientific, Singapore. Dymond A., Crandall P. (1973) Intracerebral temperature changes in patients during spontaneous epileptic seizures. Brain Research 60:249-254. Gopalsami N., Osorio I., Kulikov S., et al. (2007) SAW microsensor brain implant for prediction and monitoring of seizures. Accepted for publication in the IEEE Sensors Journal. Pennes H. (1948) Analysis of tissue and arterial blood temperature in the resting human forearm. J. Appl. Physiol. 1:93-122. Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Lyubynskaya, Tatiana BioFil, Russian Federal Nuclear Center-VNIIEF 37 Prospekt Mira Sarov, Nizhny Novgorod reg. Russia [email protected]

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In vivo dosimetry with diodes in radiotherapy patients treated with four field box technique A. Strojnik Institute of Oncology Ljubljana/Department of Radiophysics, Ljubljana, Slovenia Abstract— Two diodes have been calibrated as in vivo dosimeters for entrance and exit dose measurements in radiotherapy with 15 MV photon beams. Their response dependencies on dose, dose rate, focus skin distance, field size, gantry angle and patient thickness have been investigated. 1243 routine measurements have been performed in 302 rectal and prostate cancer patients irradiated with four field box technique. Measurement statistics is presented. Keywords— Radiotherapy, In vivo dosimetry, Diodes

I. INTRODUCTION Radiotherapy is a cancer treatment modality which exploits medical benefits of ionizing radiation. Its outcome strongly depends on the accuracy of absorbed radiation dose to the tumor and the surrounding healthy tissue. An important part of treatment quality control is in vivo dosimetry: small dosimeters attached to the patient’s skin measure absorbed dose at beam’s entrance into the patient’s body or its exit. Measurements are subsequently compared to the values obtained by the radiotherapy planning system and in case of unacceptable difference immediate action to detect and remove the source of error is undertaken. This paper describes calibration of two commercial semiconductor diodes as in vivo dosimeters and presents the results of a one year clinical routine. II. MATERIALS AND METHODS A properly calibrated semiconductor diode connected to a suitable electrometer can be used as a dosimeter: barrier voltage across the depletion region of the p-n junction propels the charge carriers generated by the radiation. The charge collected by the electrometer is proportional to the absorbed dose. To increase the accuracy by measuring absorbed dose close to the depth dose maximum, commercial diodes are equipped with a build-up cap.

Fig. 1 A cross-section of a dosimetric diode: 1 – build-up cap; 2 – detector chip. Radius of the build-up cap is approximately 5 mm. Diameter of the active area is 2 mm. Connectors to the electrometer exit to the right of the picture. A. Calibration The EDP-20 p-type silicone diode produced by Wellhofer Scanditronix has a build-up cap equivalent in attenuation to 20 mm of water and is intended for in vivo dosimetry in 10 – 20 MV photon beams. Two diodes of this type have been calibrated against an ionization chamber at reference conditions in a 15 MV photon beam from a Varian 2100CD linear accelerator, following the guidelines in [1] and [2]. In reference conditions each diode has been taped to a slab of Plastic Water at a distance of 100 cm from the accelerator focus, in the center of a 10 cm x 10 cm open treatment field, with gantry angle set to 0°. The ionization chamber has been irradiated with the same treatment parameters at depth dose maximum. In addition to the calibration factor F correction factors accounting for non-reference conditions (different focus surface distances – CFSD, field sizes – CFS, wedged filters – CW and exit dose measurement – CEXIT) have been determined. During each set of measurements all other parameters apart from the one in question have been kept at reference values. In the case of exit dose correction factor gantry has been rotated to 180° and focus surface distance to the near side of the slab has been set to 100 cm. Signal dependency on gantry angle has been investigated up to 30°.

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Fig. 2 Irradiation of a diode in reference (left) and non-reference conditions: 1 – linear accelerator focus (photon source); 2 – collimator jaws; 3 – diode; 4 – Plastic Water phantom; 5 – treatment couch. Field size (FS, FS’) is defined at the isocenter, 100 cm from the focus. Focus surface (skin) distance (FSD, FSD’) is measured from the linac focus to the phantom surface (patient’s skin). A wedged beam has a wedge filter inserted below collimator jaws (not shown in the picture). From the electrometer reading R the entrance dose measured by the diode has been calculated as

D = R ⋅ F ⋅ C FSD ⋅ C FS ⋅ CW

(1)

whereas the exit dose has been calculated as

D = R ⋅ F ⋅ C EXIT

(2)

Throughout the calibration and in vivo measurements each diode has been connected to a dedicated channel on an emX Scanditronix electrometer. Electrometer has been connected to a computer running DPD12-pc software also provided by Scanditronix Wellhofer. Dark current drift and offset of the assembly have been measured and accounted for. The diodes have been recalibrated periodically due to sensitivity degradation linked to radiation damage. B. In vivo measurements The two diodes have been used in routine measurements in rectal and prostate cancer patients treated with four field box technique. With this technique beams strike target from four directions, gantry angle occupying values of 270°, 0°, 90° and 180°. Such configuration allows a diode taped to the patient’s skin on the 0° beam’s axis to measure not only 0° beam’s entrance dose but also 180° beam’s exit dose. The same principle applies to 90° and 270° beams. In case of patient having an artificial hip the beam passing through it is removed from the treatment plan and the anteroposterior beams are wedged to obtain homogeneous dose coverage over the target. Routine: After a patient is accurately set-up in the correct treatment position (either prone or supine) as established at

the CT simulator, the diodes are taped to the patient's skin at the entrance points of 0° and 90° beams. As the treatment starts with the accelerator gantry at 270° rotating clockwise the first measurement is of the 270° beam's exit dose, followed by 0° beam's entrance dose, then 90° beam's entrance dose and concluding with 180° beam's exit dose. Measurement readings are multiplied by appropriate calibration and correction factors as in equations 1 and 2 and compared to the values calculated by the planning system. If the difference exceeds the tolerance level of 5% for entrance dose (as proposed by [2]) or 8% for exit dose a thorough investigation of treatment parameters is performed together with a scrupulous review of the treatment plan; in vivo dosimetry is repeated at the next treatment session and focus skin distances are carefully measured to verify the correct placement of the dosimeters with respect to the accelerator’s focus. If the problem persists, the treating radiation oncologist is consulted: if portal images of the treated area are satisfactory the number of monitor units of the problematic treatment field is adapted. Another session of in vivo dosimetry is required. Besides regular checks diodes are recalibrated at a slightest indication of a systematic error. At Institute of Oncology Ljubljana in vivo dosimetry is performed at the second treatment session for every patient (portal imaging at the first session) and after any alterations of treatment parameters. III. RESULTS C. Calibration Diodes have been calibrated for clinical dose rates of approximately 3 Gy/min. Signal has remained constant (within 2‰) throughout dose rate interval between 1 Gy/min and 6 Gy/min. Diode response linearity has been tested for clinical doses between 10 cGy and 10 Gy with the results within 2‰. The calibration factors F could not have been expressed in terms of Gy/As because DPD12-pc software presents the signal from the electrometer in arbitrary dosimetric units instead of As. The manufacturer specifies detector sensitivity to be around 30 nAs/Gy. Diodes have been irradiated in geometric conditions which are most common in patient treatment. This includes focus skin distances from 80 cm to 115 cm with field sizes between 5 cm x 5 cm and 30 cm x 30 cm. Diodes have also been irradiated with wedged beams, nominal inclinations of hard wedges being 15°, 30° and 45°. Correction factors are presented in Tables 1, 2 and 3. Exit dose measurements have been performed with thicknesses of the Plastic Water phantom ranging from 20 cm to 35 cm simulating different patient thicknesses. Exit

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dose correction factor has been determined to be almost constant (within 1%) and has been established to be 1,10 and 1,12 for diodes 1 and 2 respectively. The influence of gantry angles up to 30° has been below 1%. Since it is difficult to determine the angle between the beam axis and the patient’s skin surface on which the diode is taped and since with the four field box technique described in the previous section all beams are close to perpendicular, gantry angle correction factors have been omitted. Temperature dependence has not been investigated. It is too difficult if not impossible to monitor the temperature of the detector during patient treatment. The diode manufacturer claims the increase of diode sensitivity is approximately 2,5‰ per °C. According to [1] the influence of temperature is negligible. It is estimated that during the time of use the diodes have absorbed approximately 300 Gy. Sensitivity degradation of about 1% has been observed. Table 1

Focus skin distance correction factors

Focus Skin Distance (cm)

Correction factor for diode 1

Correction factor for diode 2

80 85 90 95 100 105 110 115

0,962 0,982 0,989 0,994 1 1,006 1,011 1,016

0,965 0,979 0,988 0,994 1 1,007 1,012 1,016

Table 2

Field size correction factors

Field Size (cm x cm)

Correction factor for diode 1

Correction factor for diode 2

5 x5 10 x 10 15 x 15 20 x 20 25 x 25 30 x 30

0,997 1 1,002 1,004 1,006 1,008

0,998 1 1,004 1,005 1,008 1,011

Table 3

Wedge correction factors

Wedge (°)

Correction factor for diode 1

Correction factor for diode 2

15 30 45

1,007 1,015 1,016

1,013 1,017 1,019

893

D. In vivo measurements From January 2006 to February 2007 in vivo dosimetry has been conducted in 326 treatment sessions. Measurement statistics is presented in Table 4. In 27 (9%) out of 302 patients in vivo measurements have exceeded the tolerances. In 6 (22%) of the 27 also repeated measurements have resulted beyond acceptable levels. In 1 of the above 6 patients a closer inspection has revealed a false CT image set had been assigned to the patient. A new therapy plan has later been created with the correct CT image set. In another of the above 6 patients the source of error has proven to be a set of incomplete CT images: due to the size of the patient, the outmost parts of the patient’s hips had not been captured by the CT scanner. To rectify the problem focus skin distances in lateral fields have been measured and the number of monitor units has been adapted. Isocenter marks had been incorrectly drawn on the patient’s skin in two cases: in both the error has been simultaneously discovered by in vivo dosimetry and electronic portal imaging. Marks have been correctly redrawn on the simulator. In the remaining two of the six patients the source of error has not been discovered. It has only been assumed that the patients’ bowels have not been emptied before radiotherapy as they have been prior to CT scan. As portal images have been evaluated by radiation oncologist as acceptable the number of monitor units has been suitably modified. After the corrections in vivo dosimetry has been repeated and resulted within tolerance levels in all 6 cases. In some of the prostate cancer patients treated in supine position a probable reason for the initial exceeding of tolerances has been patient’s body hair obstructing the taping of the diode to the patient’s skin. The problem has mostly been solved by moving the diode to a hairless spot of skin still within the treatment field. In some of the rectal cancer paTable 4

Measurement statistics Diode 1

Diode 2

Number of entrance dose measurements - exceeding tolerance at initial session - exceeding tolerance at repeated session Average difference between measured and expected entrance dose Standard deviation of entrance dose differences

317 17 (5%) 3 (1%) 0,0%

326 27 (8%) 5 (2%) 1,0%

3,0%

2,7%

Number of exit dose measurements - exceeding tolerance at initial session - exceeding tolerance at repeated session Average difference between measured and expected exit dose Standard deviation of exit dose differences

295 24 (8%) 6 (2%) -0,2%

305 19 (6%) 6 (2%) -0,6%

6,7%

4,6%

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tients in prone position the solution to large deviations calculated from the initial measurements has been moving the dosimeter from a sloped to a nearby horizontal area, hence avoiding large angles between 0° beam axis and diode. IV. DISCUSSION So far in vivo dosimetry hasn’t detected any treatment equipment malfunction. The source of problems encountered during one year routine has either been patient data (CT images) or patient set-up. A quantity which is very influential in dose delivery and at the same time influenced by patient set-up is focus skin distance. Table 5 facilitates the discovery of source of error in measurements with extreme deviations. Entrance dose tolerance level of 5% allows inaccuracies of roughly 2,5 cm in focus skin distance. Similarly for exit dose a tolerance level of 8% allows errors of about 1,5 cm in patient thickness. As both discrepancies could easily be measured with an optical distance meter, a quick focus skin distance check could prove a valuable quality assurance procedure in departments without in vivo dosimetric equipment. Table 5

Error detection with opposite treatment fields

Entrance dose error (beam 0°) < –5%

Exit dose error (beam 180°) > +8%

> +5%

< –8%

Probable source of error Patient too thin or treatment couch too low Patient too thick or treatment couch too high

CONCLUSIONS Complementary to portal imaging in vivo dosimetry provides dosimetric information about the actual treatment delivery and represents another safety measure in the treatment process. In one year since its implementation it has revealed and prevented 6 cases of inaccurate treatment.

ACKNOWLEDGMENT The study was done partly within a national program Development and Evaluation of New Approaches to Cancer Treatment P3-0003(D) financially supported by the Slovenian Research Agency (ARRS).

REFERENCES 1. 2.

Van Dam J, Marinello G (1994) Methods for in vivo dosimetry in external radiotherapy. ESTRO Booklet No. 1, ISBN 90-804532-5 Huyskens DP, Bogaerts R, Verstraete J, Lööf M, Nyström H, Fiorino C, Broggi S, Jornet N, Ribas M, Thwaites DI (2001) Practical guidelines for the implementation of in vivo dosimetry with diodes in external radiotherapy with photon beams (entrance dose). ESTRO Booklet No. 5, ISBN 90-804532-3 Address for correspondence Andrej Strojnik Department of Radiophysics Institute of Oncology Ljubljana Zaloska cesta 2 SI – 1000 Ljubljana Slovenia Phone: (+386) 1 5879 631 E-mail: [email protected]

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Interaction between charged membrane surfaces mediated by charged nanoparticles J. Pavlic1,2, A. Iglic1, V. Kralj-Iglic3, K. Bohinc1,2 1

2

Faculty of Electrical Engineering, Trzaska 25, 1000 Ljubljana, Slovenia University College for Health Studies, Poljanska 26a, 1000 Ljubljana, Slovenia 3 Faculty of Medicine, Lipiceva 2, Ljubljana, Slovenia

Abstract— The interaction between charged membrane surfaces, separated by a solution containing charged nanoparticles was studied experimentally and theoretically. The nonlocal theory for the nanoparticles was developed where finite size of nanoparticles and spatial distribution of charge within a particle were taken into account. It was shown that for large enough membrane surface charge densities and large enough dimensions of nanoparticles, the force between equally charged membranes may be attractive due to spatially distributed charges within the nanoparticles. Keywords— Nano particles, charge density, membrane surface

I. INTRODUCTION In biology, there are many phenomena which motivate the studies of electrostatic interaction between charged macroions in the electrolyte solution. The condensation of DNA can be induced by the presence of multivalent counterions [1, 2], and corresponds to the packing of DNA in viruses. The complexation of DNA with positively charged colloidal particles [3, 4] was observed, which corresponds to nucleosome core particles and the basic fiber of chromatin. Network formation in actin solutions [5] is the consequence of the attractive interactions between cytoskeletal filamentous actin molecules mediated by multivalent ions. The aggreation of rod-like M13 viruses is induced by divalent tunable diamin ions [6]. In this work we study interaction between negatively charged membrane surfaces of giant phospholipid vesicles in the sugar solution containing multivalent rod-like ions. The negative charge of the phospholipid bilayers was generated by a certain proportion of the phospholpid cardiolipin while the multivalent cations are represented by Spermidine and Spermine. Adhesion of phospholipid vesicles due to the presence of Spermidine or Sperimine in the solution was observed. To describe the observed features, a theoretical model was constructed where the phospholipid membranes are described as infinite flat surfaces bearing uniformly distributed charge while the Spermidine and Spermine are considered as rod-like counterions. Due to the specific

shape of these molecules which bear charge at their ends, it is taken that the charge distribution within Spermidine and Spermine is represented by two effective charges e, separated by a distance l. The system is described by the nonlocal theory of the electric double layer, where the shape and the orientational restrictions of the rod-like ions is considered. II. MATERIALS AND METHODS A. Spermidine and Spermine polyamine molecules Polyamines Spermidine and Spermine (Fig. 1) were purchased from Sigma-Aldrich. The Spermidine is tri-valent, while the Spermine has the valency of four. They are positively charged (amino groups contribute to the charge). Spermidine and Spermine were obtained in powder and were dissolved in distilled water to the final concentration of 2mg/ml.

Fig. 1 Schematic presentation of Spermidine and Spermine polyamines.

B. Giant phospholipid vesicles (GPV) GPVs were prepared at room temperature (23°C) by the modified electroformation method [7]. The synthetic lipids cardiolipin (1,1'2,2'-tetraoleoyl cardiolipin), POPC (1palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and cholesterol were purchased from Avanti Polar Lipids, Inc. Ap-

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propriate volumes of POPC, cardiolipin and cholesterol, all dissolved in a 2:1 chloroform/methanol mixture, were combined in a glass jar and thoroughly mixed. POPC, cholesterol and cardiolipin were mixed in appropriate proportions such as 2:2:1. Volume of 20 µl of lipid mixture was applied to the platinum electrodes. The solvent was allowed to evaporate in a low vacuum for 2 hours. The coated electrodes were placed in the electroformation chamber which was then filled with 3 ml of 0.2 M sucrose solution. An AC electric voltage with an amplitude of 5 V and a frequency of 10 Hz was applied to the electrodes for 2 hours, which was followed by 2.5 V and 5 Hz for 15 minutes, 2.5 V and 2.5 Hz for 15 minutes and finally 1 V and 1 Hz for 15 minutes. The content was rinsed out of the electroformation chamber with 5 ml of 0.2 M glucose and stored in plastic test tubes at 4oC. The vesicles were left for sedimentation under gravity for one day and were then used for a series of experiments.

Fig. 2 The solution of giant phospholipid vesicles containing 20% weight ratio of cardiolipin few minutes after the addition of Spermidine to the solution with vesicles.

C. Observation Vesicles were observed by an inverted microscope Zeiss Axiovert 200 with phase contrast optics and recorded by the Sony XC-77CE video camera. The solution containing vesicles was placed into observation chamber made from cover glasses and sealed with grease. The larger (bottom) cover glass was covered by two smaller cover glasses, each having a small semicircular part removed at one side. Covering the bottom glass by two opposing cover glasses formed a circular hole in the middle of the observation chamber. In all experiments the solution of vesicles (45 µl) was placed in the observation chamber. The solution containing the substance under investigation (Spermidine or Spermine) was added into circular opening in the middle of the observation chamber. III. EXPERIMENT The solution of GPVs contains a heterogeneous population of vesicles of different shapes and sizes. The vesicles are subject to thermal fluctuations of their shape. Few minutes after the addition of either Spermidine or Spermine to the solution with GPVs the thermal fluctuations of vesicles diminish while the vesicles adhere to each other and to the ground. Further away from the site of insertion of Spermidine or Spermine, the process of adhesion may take up to 30 min. Vesicles slowly approach each other, but once acquiring a small distance they adhere to each other. The complexes formed by the adhesion of charged giant phospholipid vesicles after the addition of Spermidine and Spermine is shown in (Fig. 2) and (Fig. 3), respectively.

Fig. 3 A complex of liposomes formed by adhesion of giant phospholipid vesicles containing 20% weight ratio of cardiolipin few minutes after the addition of Spermine to the solution with vesicles. IV. MATHEMATICAL MODEL We consider an aqueous electrolyte solution containing divalent rod-like ions. The solution is sandwiched between two equally charged planar surfaces with surface charge density σ. The two surfaces of area A are separated by a distance D. The description of the system is based on the non-local theory of the electric double layer where the rodlike ions are characterized by positional and orientational degrees of freedom. The energy is therefore stored in the electrostatic field as well as in the translational and orientational entropy of the rod-like ions. The electrostatic free energy of the system is

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Interaction between charged membrane surfaces mediated by charged nanoparticles D

D

F 1 = Ψ'2 dx + ∫ [n( x) ln[v0 n( x)] − n( x)]dx + AkT 8πl B ∫0 0 D

(1)

∫ n(x) < p(l | x)[ln p(l | x) + U (x, l)] > dx + 0

D

D

0

0

∫ n(x)λ(x)[< p(l | x) > −1]dx + μ ∫[−2n(x) −

2σ ]dx De

where Ψ is the reduced electrostatic potential, μ is the reduced chemical potential, U(x,l) is the external reduced potential of the charged wall, n(x) is the local concentration of reference charges of multivalent rod-like ions, p(l|x) is the conditional probability density describing the position of the second charge on the rod-like counterion if the first charge is located at x, lB =e2/4πεkT is the Bjerrum length, ε is the dielectric constant of water, k is the Boltzmann constant, T is the absolute temperature, v0 is the volume of the divalent ion while < ... > indicates the averaging over all possible orientations. Two constraints are added to the free energy describing the normalization condition for the probability density and the electro-neutrality of the system. The equilibrium state of the system is obtained by the minimization of the free energy (1). The variational problem is stated by means of integro-differential equation which is solved numerically. As a result we obtain the consistently related equilibrium positional and orientational distribution functions for the counterions and the equilibrium free energy of the system. The dependence of the equilibrium free energy on the distance between the

2.5

[1/nm2 ]

2

1.5

F /AkT

1 σ = 0.1 As/m2 0.5

σ = 0.033 As/m2

0

−0.5

1

2

3

4

5

6

7

8

D [nm]

Fig. 4 The free energy as a function of the distance between two equally charged surfaces. The model parameter is l = 5 nm.

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charged surfaces reveals the nature of the interaction between the surfaces. If the free energy increases with increasing distance between the surfaces, then the force between the surfaces is attractive. The equilibrium distance between the surfaces is obtained at the mininum of the dependence of the free energy on the distance D. The free energy of the system as a function of the distance between two negatively charged surfaces is shown in (Fig. 4). For large enough σ the free energy first decreases with increasing distance D, reaches a minimum and then increases. For small σ the free energy monotonously decreases with increasing distance D. The minimum of the free energy is more pronounced for longer rod-like ions. The insets show a scheme of the most probable orientation of rod-like ions at minimal free energy. V. DISCUSSION AND CONCLUSIONS The presented model provides a simplified analysis of the problem. In this paper we studied the interaction between negatively charged surfaces mediated by positively charged tri-valent Spermidine and four-valent Spermine. The experiments showed the adhesion of GPVs after the addition of Spermidine and Spermine. This means that even though the surfaces are negatively charged they are attracted to each other. In order to better understand the experimental effects we considered the theoretical model, where the Spermidine and Spermine are considered as rod-like ions [8] and GPVs are described by two equal planar surfaces. The theory confirmed the attraction of negatively charged surfaces mediated by charged nano particles. The attraction between equally charged surfaces originates from correlations between the multivalent counterions, which are not considered in the mean field PoissonBoltzmann theory [9]. Theoretically, the Monte Carlo (MC) simulations of Guldbrand et al. [10] have first confirmed the existence of attraction between equally charged surfaces immersed into the solution composed of divalent ions in the limit of high surface charge density, which were originally predicted by Oosawa [11]. Further, MC simulations show that the attractive interaction between equally charged surfaces may arise for high surface charge density, low temperature, low relative permittivity and polyvalent counterions [12]. Also the anisotropic hypernetted chain approximation within the primitive electrolyte model for divalent ions was used [13, 14], where the ions were described as charged hard spheres immersed in a continuum dielectric medium. At moderate surface-surface distances and high surface charge density the attraction between the equally charged surfaces was found.

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REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9.

Bloomfield V. A. (1996) Curr. Opin. Struct. Biol. 5: 334 Teif V. (2005) Biophys. J. 89(4): 2574-2587 Raedler J. O., Koltover I., Saldit T., Safinya C. R. (1997) Science 275: 810-814 Gelbart W. M., Bruinsma R. (2000) Physics today 53: 38 Angelini T. E. (2003) Proc. Natl. Acad. Sci. USA 100: 8634 Butler J. C., Angelini T. (2003) Phys. Rev. Lett. 91: 028301 Angelova M. I., Soleau S. Meleard P. Faucon J. F., Bothorel P. (1992) Prog. Colloid. Polym. Sci. 89:127-31. Bohinc K., Iglič A., May S. (2004) Europhys. Lett. 68(4): 494-500 Carnie S., McLaughlin S. (1983) Biophys. J. 44:325

10. 11. 12. 13.

Guldbrand L. (1984) J. Chem. Phys. 80: 2221 Oosawa F. (1968) Biopolymers 6: 1633 Svensson B., Joensson B. (1984) Chem. Phys. Lett. 108: 580 Kjellander R. (1996) Ber. Bunsenges. Phys. Chem. 100(6): 894-904 14. Kjellander R. (1988) J. Phys. France 49:1009 Author: Institute: Street: City: Country: Email:

Janez Pavlič University College for Health Studies Poljanska 26a Ljubljana Slovenia [email protected]

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Laminar Axially Directed Blood Flow Promotes Blood Clot Dissolution: Mathematical Modeling Verified by MR Microscopy J. Vidmar1, B. Grobelnik1, U. Mikac1, G. Tratar2, A. Blinc2 and I. Sersa1 1

Condensed Matter Physics Department, Jozef Stefan Institute, Ljubljana, Slovenia Department of Vascular Diseases, University of Ljubljana Medical Centre, Slovenia

2

Abstract— Understandig process of thrombolysis is a key for a corresponding medical treatment. Thrombolysis of nonocclusive blood clots is significantly accelerated by axially directed blood plasma flow. When fast blood flow occurs, the increase of the dissolution rate is too big that it could be explained just by better permeation of the thrombolytic agent into the clot and more efficient biochemical degradation. Viscous forces caused by shearing of blood play an essential role in addition to the known biochemical fibrinolytic reactions. We developed an analytical mathematical model based on a hypothesis that clot dissolution dynamics is proportional to the power of the blood plasma flow dissipating along the clot. The model assumes cylindrical non-occlusive blood clots with centrally placed flow channel and the flow is assumed laminar at a constant rate all times during dissolution. Effects of sudden constriction on the flow and its impact on the dissolution rate are considered as well. The model of clot dissolution was verified experimentally by dynamic magnetic resonance (MR) microscopy in in-vitro circulation system containing plasma with a magnetic resonance imaging contrast agent and recombinant tissue-type plasminogen activator (rt-PA). Sequences of dynamically acquired 3D low resolution MR images of entire clots and 2D high resolution MR images of clots in an axial cross-section were used to evaluate the dissolution model by fitting it to the experimental data. The experimental data fitted well to the model, and confirmed our hypothesis. Keywords— flow, thrombolysis, blood clots, MR microscopy

I. INTRODUCTION Restoring vessel patency by dissolving blood clots is the main goal of thrombolytic therapy, which soared in the area of treating myocardial infarction during the last two decades [1, 2] but is now more moving into the realm of treating acute ischemic stroke [3]. In addition, thrombolytic treatment is valuable when dealing with hemodynamically significant pulmonary embolism [4, 5] and acute/subacute arterial thrombosis [6]. Biochemically, thrombolysis starts with activation of the proenzyme plasminogen into the active serine protease plasmin [7]. Several plasminogen activators, such as recombinant tissue type plasminogen activator (rt-PA) or its modified variants reteplase and tenekteplase may be used in pharmacological doses to initiate thrombolysis [8]. As an

effective and safer alternative to plasminogen activators, local infusion of plasmin into the clot has been sucessfully applied in experimental animals [9]. The final outcome of thrombolysis depends on properties of the thrombolytic agent, clot structure and characteristics of molecular transport into the clot [10]. Thrombolysis at low-velocity axially directed blood flow has already been studied and mathematically modeled. Pleydell and coworkers [11] developed a mathematical model of post-canalization thrombolysis at low-velocity flow that takes into account the changing concentrations of the major components of the fibrinolitic system. However, relatively little is known about high-velocity axially directed blood flow influencing thrombolysis of nonocclusive clots. The results of Sakharov and Rijken [12] as well as our own results [13] show that high-velocity plasma flow significantly enhances dissolution of blood clots when favorable biochemical conditions are present. We have already presented a model that takes into account the mechanical forces generated at the clot-plasma interface in addition to the biochemical conditions [14]. Our main assumption was that viscous forces of blood flow, that are responsible for the surface erosion of the clot in the flow channel, act in parallel with the fibrinolytic system [14]. Presented paper refines our initial model by taking into account the effects of sudden blood vessel constriction at the site of non-occlusive thrombosis and evaluates its impact on the rate of clot dissolution. The model was verified experimentally by dynamic magnetic resonance microscopy of non-occlusive blood clots dissolving in in-vitro circulation system. II. THEROY A. Blood Velocity Model Blood velocity profile in a normal vessel is according to the Poiseuille’s law parabolic. After entering the flow channel of the clot this profile progressively changes from initially flat profile to the parabolic profile as blood moves downstream the channel (Figure 1). In the transition region that extends from the entrance to the depth known as the

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B. Rate of Clot Dissolution

z0 R∞

The clot begins to dissolve after adding a pharmacologic concentration of a thrombolytic to the flowing blood. The channel along the clot expands radially as thin layers of the clot are gradually removed. We assume that for every biochemical setting, the rate of clot dissolution is proportional to the dissipated power of the blood flowing along the clot. The work dW done by the flowing blood to the volume element of the clot in the flow channel in time dt is proportional to the shear velocity ∂v / ∂r squared

z R blood clot

Fig. 1 Blood velocity profile transformation after entering the flow channel of the clot.

entrance length [15] the blood adjacent to the wall is progressively retarded due to shear forces at the vessel wall while blood in the core region is accelerated to maintain the same flow rate. At distances from the entrance larger than the entrance length the region with dominating viscous effects, also known as the boundary layer (yellow region in Fig. 1), covers the whole cross-sectional area of the flow channel and the flow profile is then fully developed The boundary layer thickness δ increases with the square root of the distance from the entrance point z

⎧ R z / z0 ; z < z0 δ ( z) = ⎨ ⎩ R ; z ≥ z0

(1)

The boundary layer extends over the whole channel cross-section (δ=R) at entrance distances z equal or lager to the entrance length z0. The entrance length is proportional to the channel diameter d=2R and the Reynolds number [15]

z0 = 0.06 d Re =

0.24 ρ ΦV

π

η

.

(2)

A simple model for velocity profile in the entrance region can be constructed knowing the boundary layer axial profile (1). The model assumes a flat velocity profile in the core region that continuously converts into a parabolic velocity profile within the boundary layer ending with zero velocity at channel walls. Combining these conditions with conservation of the flow rate and with boundary layer axial profile (1) yields the following velocity profile as a function of the radial distance r and the entrance distance z 2 2 v0 R ⎧ ⎪ R2 + R − δ (z) 2 ( ) ⎪ v(r , z ) = ⎨ 2 2 2 ⎪ 2 v0 R ( R − r ) ⎪⎩ R 4 − ( R − δ ( z ) )4

;

r < R − δ (z)

. ;

r ≥ R − δ (z)

(3)

⎛ ∂v

dW = λ Sη ⎜

⎝ ∂r

⎞

r =R

2

( z ) ⎟ dt ,

(4)

⎠

where η is the blood viscosity, λ is the thickness of the volume element and S is the surface area of the volume element that is exposed to the streaming blood in the flow channel. The shear velocity of the flowing blood in contact with the clot (at r=R) can be calculated from (3)

∂v ∂r

( z) = − r=R

4 v0 R

3

R − ( R − δ ( z) ) 4

4

.

(5)

The work dW of the flowing blood in contact with the clot is used for removal of a thin layer of the clot of thickness dR. The work is proportional to the volume dV of the removed layer dW = c dV = c S dR, where c is the proportionality constant incorporating the efficiency of the thrombolytic agent. As every thrombolytic agent needs time to starts its enzymatic reaction the constant c is initially very large and after time τ starts approaching the final value c∞ at a rate Δ. The activation of the thrombolytic agent can be described by a Fermi like function 1 c (t )

=

1

1

c∞ 1 + exp((τ − t ) / Δ )

.

(6)

Replacing the work and the thrombolytic agent efficiency constant in equation dW = c S dR with expressions in (4), (5) and (6) yields a differential equation for the clot dissolution rate with the following solution ⎧ ⎪ R ⎡⎛ R0 ⎪ ∞ ⎢⎢⎜⎝ R∞ ⎪ ⎣ R( z, t ) = ⎨ ⎪ ⎪ ⎩⎪

7

⎞ Δ ⎛ 1 + exp((t − τ ) / Δ ) ⎞ ⎟ + T ln ⎜ 1 + exp( −τ / Δ ) ⎟ ⎝ ⎠ ⎠ 7

(1 − (1 −

z / z0

)) 4

1

2

⎤7 ⎥ ⎦⎥

;

z < z0

1

R∞

⎡⎛ R0 ⎞ 7 Δ ⎛ 1 + exp((t − τ ) / Δ ) ⎞ ⎤ 7 ⎢⎜ ⎟ + ln ⎜ ⎟⎥ ⎣⎢⎝ R∞ ⎠ T7 ⎝ 1 + exp( −τ / Δ ) ⎠ ⎦⎥

;

z ≥ z0

(7)

here R0 is the initial radius of the flow channel at beginning of the dissolution,

__________________________________________ IFMBE Proceedings Vol. 16 ___________________________________________

Laminar Axially Directed Blood Flow Promotes Blood Clot Dissolution: Mathematical Modeling Verified by MR Microscopy

R∞ is the radius of the normal blood vessel and T7 is a time constant equal to 1 T7

16λη ΦV

1.

861

High velocity

2

=

(8)

π c∞ 2

According to the model in equation (7) the dissolution completes in time approximately equal to the parameter T7. For a convenience, we introduce a parameter reflecting the occlusion level defined as the ratio between the crosssectional area of the clot and the cross-sectional area of the normal non-occluded vessel 2

⎛ R( z, t ) ⎞ ⎟ . ⎝ R∞ ⎠

x( z , t ) = 1 − ⎜

(9)

III. MATERIALS AND METHODS Clotting of blood, that was collected form a healthy male volunteer, was induced in vitro by adding calcium (50 μl CaCl2 at 2 mol/l per ml of blood) and thrombin in a final concentration of 1 NIH unit/ml of blood. Non-retracted clots (retraction was inhibited by the phosphodiesterase inhibitor UDCG 212) were formed in cylindrical glass tubes with an inner diameter of 3 mm and length of 3 cm. The clots were pierced lengthways on the outside by a needle with a diameter of 0.7 mm to create a flow channel along the clot. The glass tube with a clot was then connected by a flexible hose to a pump generating a constant pressure of either 15000 Pa or 3000 Pa, which represent mean arterial and venous pressures in humans. The artificial circulation system was in each experiment filled with approximately 0.5 l of blood plasma at room temperature. The viscosity of blood plasma is 1.8 times higher than is the viscosity of water whereas its density is about 3.5 % higher than the density of water [15]. Two blood flow velocity regimes were tested: high velocity regime corresponding to shear forces generated in the arterial system and low velocity regime corresponding to shear forces in the venous system. In the high velocity regime volume flow rate was equal to 1.64 ml/s, initial average blood velocity and the Reynolds number were equal to 4.26 m/s and 1660 and the entrance length was equal to 70 mm, while in the low velocity regime volume flow rate was equal to 0.074 ml/s, initial average blood velocity and the Reynolds number were equal to 0.19 m/s and 75 and the entrance length was equal to 3.1 mm. In both velocity regimes initial occlusion level was equal to x = 0.946. Artificial circulation system was set in a horizontal bore 2.35 T superconducting magnet (Oxford, UK) – a part of the

8.

0 min

7.

2.

Low velocity

4 min

6.

8

5.

12 min 4.

16 min

Fig. 2 MR images of blood clot dissolution

MRI system that consisted also of a TecMag NMR console and Bruker NMR probes and gradients. First, the glass tube with the clot was inserted into a RF probe in the centre of the MRI magnet. Then, hoses were connected to the glass tube with clot and to the pump immersed in a container filled with plasma and the circulation system was started. After that dynamical MR imaging was started. First 10 minutes, clots were imaged without the thrombolytic agent in the circulation system to assure that clot dissolution was not caused by mechanical erosion alone, then the thrombolytic agent recombinant tissue activator of plasminogen rt-PA (Actylise, Boehringer, Germany) was added in a pharmacologic dose of 2 μg/ml to the plasma as well as the MR imaging contrast agent Gd-DTPA (Magnevist, Berlex Lab., Germany) at 1 mmol/l and dynamically imaging continued for another 40 minutes. The imaging method was the conventional spin-echo MRI technique with parameters TE/TR = 8/400 ms, imaging field of view 2 cm, imaging matrix 256 by 256 points and the slice thickness of 2 mm. Clots were imaged in transversal slice positioned centrally to the clot, 15 mm downstream from the entrance point (Fig. 2). All images were analyzed by the Image-J program which was used for measuring cross-sectional areas of the remaining clot as a function of time to get the occlusion level time dependence. These results were then divided into high and low velocity regime groups. In each group there were at least 4 clots. The experimental occlusion level data were analyzed by the mathematical model in (7). The model parameters T7, τ and Δ were extracted by finding the best fit of the model to the experimental occlusion level data. Fitting was done by the Origin computer program (Origin Lab, Northampton MA, USA). IV. RESULTS AND DISCUSSION Figure 3 shows the occlusion level time dependence, i.e., the dissolution curve, in the high and in the low velocity regime, which was obtained by analysis of dynamical MR

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J. Vidmar, B. Grobelnik, U. Mikac, G. Tratar, A. Blinc and I. Sersa 1.0

In fast flow, the dissolution rate increase is too big that it could be explained just by better permeation of thethrombolytic agent into the clot and more efficient biochemical degradation.

occlusion level x [a.u.]

0.8

0.6

high velocity low velocity

REFERENCES

0.4

1. 0.2

2.

0.0 0

500

1000

1500

2000

2500

time t [s]

3.

Fig. 3 Fit of the dissolution model to the experimental data.

image sequences as described earlier. In both velocity regimes, the dissolution model well fits the experimental MRI data. Apparent is the difference in the dissolution rate between the high and the low velocity regime. The difference is mainly due to different blood flow velocities in the channel, that result in different supply with thrombolytic agent and different mechanical work of the flowing blood to the superficial layer of the clot in the channel. The model enables also calculation of the flow channel profile at different times after dissolution beginning (Fig. 4). From the profile contours it can be clearly seen that dissolution is considerably faster at the entrance of the flow channel, due to higher shear forces of the flowing blood, than further downstream.

4.

5.

6.

7. 8.

V. CONCLUSION Mechanical forces due to blood shear velocity play in addition to enzymatic reactions of the thrombolytic agent essential role in the dissolution of non-occlusive blood clots

9.

10.

R

11. z

12. 13.

Fig. 4 Flow channel profile during clot dissolution. Profile contours are

The ISIS-2 investigators. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction (1988) J. Am. Coll. Cardiol. 12 (6 Suppl A):3A-13A The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction (1993) N. Engl. J. Med. 329:673-682 Hill M D, Buchan A M (2005) Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study CMAJ 172:1307-1312 Goldhaber S Z, Haire W D et al (1993) Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion Lancet 341(8844):507-511 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W (2002) Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism N. Engl. J. Med. 347:1143-1150 Ouriel K, Castaneda F et al. (2004) Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial J. Vasc. Interv. Radiol. 15:229-238 Collen D (1999) The plasminogen (fibrinolytic) system Thromb. Haemost. 82:259-270 Spohr F, Arntz H R et al. (2005) International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out-ofhospital cardiac arrest: the Thrombolysis in Cardiac Arrest (TROICA) Study Eur. J. Clin. Invest. 35:315-323 Marder V J, Landskroner K et al. (2001) Plasmin induces local thrombolysis without causing hemorrhage: a comparison with tissue plasminogen activator in the rabbit Thromb. Haemost. 86:739-745 Blinc A, Francis C W (1996) Transport Processes in fibrinolysis and fibrinolytic therapy Thromb. Haemost. 76:481491 Pleydell C P, David T et al. (2002) A mathematical model of post-canalization thrombolysis, Phys. Med. Biol. 47:209-224 Sakharov D V, Rijken D C (2000) The effect of flow on lysisis of plasma clots in a plasma environment Thromb. Haemost. 83:469-474 Tratar G, Blinc A et al. (2004) Rapid tangential flow of plasma containing rt-PA promotes thrombolyis of nonocclusive whole blood clots in vitro Thromb. Haemost. 91:487-496

equidistant in time.

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Laminar Axially Directed Blood Flow Promotes Blood Clot Dissolution: Mathematical Modeling Verified by MR Microscopy 14. Sersa I, Tratar G, Blinc A (2005) Blood clot dissolution dynamics simulation during thrombolytic therapy, J. Chem. Inf. Mod. 45:1686-1690 15. Nichols W W, O'Rourke M F (2005) McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, Fifth Edition. Hodder Arnold, London

Author: Institute: Street: City: Country: Email:

863

Igor Sersa Jozef Stefan Institute Jamova 39 Ljubljana Slovenia [email protected]

__________________________________________ IFMBE Proceedings Vol. 16 ___________________________________________

Modulation of the beam intensity with wax filter compensators D. Grabec and P. Strojan Institute of Oncology Ljubljana/Department of Radiotherapy, Ljubljana, Slovenia Abstract— In order to achieve homogenous dose distribution in target volume several approaches are possible. We are discussing the possibility of field intensity modulation with wax filter compensators and comparing the technique with other techniques. The case report of the head and neck region radiotherapy with the use of 2D wax filter compensator is presented. The 3D wax filter compensators technique is further discussed as a substitute to the step and shoot IMRT or to the sliding window IMRT technique. The advantages and disadvantages of the wax filter compensators are put side by side. The case of meduloblastoma treatment is outlined as the case where whit applying 3D wax filter compensators the benefit would be the greatest. Keywords—wax filter compensators, radiotherapy, IMRT techniques, meduloblastoma

I. INTRODUCTION One of the tasks in radiotherapy is to deliver the prescribed dose to the target volume. The dose should be as homogenous as possible [1, 2, 3]. The acceptable inhomogeneity is +-5% of the prescribed dose. The homogenous dose distribution can be achieved with increasing number of the properly shaped irradiating beams and with the intensity modulation of the beams (IMRT). The beam can be shaped either with individual shielding blocks or with multileaf collimator (MLC). The shaping with MLC is achieved online while individual blocks have to be manufactured in advance for every single beam. With the increasing number of beams from various directions one must be very careful not to forget the extra irradiation of the tissue that would be spared otherwise. The beam intensity can be uniformly modulated simply with filtration wedges. The nonuniform modulation within the irradiation plane can also be achieved. The way of beam intensity modulation is with compensator filter [4, 5]. Like the individual shielding block the compensator filter should be maintained in advance for every single beam that needs to be modulated. Another way to achieve the nonuniform intensity modulation of the beam is to apply sequenced irradiation, where the whole irradiation field is composed of smaller parts of different shapes (subfields) [6, 7]. Subfields are composed with different MLC positions.

Fig. 1 The irradiation field is indicated with red line. MLC is closed to the target volume indicated with violet. The modulation with the wedge (gray) was not sufficient therefore the subfield indicated with orange was added. The position of the subfield MLC is indicated with white line and the closed part is indicated with spots. To achieve homogenous dose distribution at the Institute of Oncology Ljubljana we are usually using the “standard” beam distribution [1, 2, 3] and we modulate the intensity within the beam with the application of the subfields as presented on Fig. 1. II. WAX AS FILTER COMPENSATOR MATERIAL Our choice for the filter compensator material was wax. Wax does not alter the beam quality much, besides it has low melting point (52°C), and is solid at room temperature. Wax filter compensators can be shaped with pouring the liquid paraffin wax in the negative drilled Styrofoam blocks, the same ones that are also used for fabrication of the individual shielding blocks [8]. The wax filter compensators ready to use are showed in Fig.2. The maximal possible thickness of the compensators is the thickness of the Styrofoam blocks i.e. 8 cm. The measured beam intensity reduction by 8 cm wax filter is 30% for 5MV (Philips SL 5), 25% and 20 % for 6MV and 15MV respectively (Electa Synergy platform).

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 867–870, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

868

D. Grabec and P. Strojan

Fig. 2 The wax filter compensators. The Styrofoam blocks hold both, the wax compensators and the individual shielding blocks of Wood alloy. The blocks are fixed on the positioning trays. The central hole was drilled in each foam block in order to see the center of the optical fields.

The depth dose measurements of filtered and nonfiltered beams at Electa Synergy platform revealed the slight beam hardening that were observed as the milimetric shifts of absorbed dose maxima. The tissue phantom ratios at 10 and 20 cm of the filtered and nonfiltered beam were also compared (TPR 20/10) and the comparison also did not reveal the significant beam hardening. III. THE CASE REPORT: 2D WAX FILTER COMPENSATORS Since with the standard technique the optimized planed absorbed dose distribution in the presented case of oropharings irradiation was not acceptable, the irradiation with 2D wax filter compensator was considered. The 2D wax filter compensator is a compensator of uniform thickness that is introduced in the certain region of the field. The patient was scheduled for irradiation with 5 MV on the linear accelerator Philips SL-5. The standard irradiation technique consisted of the two opposed lateral fields shaped to the desired shape with the individual shielding blocks. The optimized dose distribution was calculated with the Multidata planning algorithm using three CT slices (Multidata System International Corp., St. Louis, Missouri, USA). The planed absorbed dose distribution as is presented on Fig.3 revealed the inhomogenieties that ranged from 94% to 113% of the prescribed dose. The absorbed dose inomogenieties can be reduced applying the compensator filter, as presented on Fig.4. The optimal reduction of beam intensity was 15% in the indicated region. Applying such compensator, the planed dose inhomogenieties are reduced to the acceptable level.

Fig. 3 The optimized dose distribution was calculated using three CT slices. The inhomogenieties inside the treated volume were 19 % of the prescribed dose which is not acceptable. The regions of different absorbed doses, expressed in the percentage of prescribed dose, are colored: 95 % ≤ green 2), but improved his tracking and more than halved tracking error (rrmse < 1). Addition of FES significantly increased his tracking performance, resulting in lower tracking error. First evaluation results of training with system for upper extremity sensory-motor augmentation are encouraging in means of muscle strengthening and reducing the force tracking error which implies to the improvement of grip force control.

(a) Tracking result of Task A, rrmse = 2.46 80

ACKNOWLEDGMENT

60 F [N]

40 20 0 -20

0

20

40

60

80 t [s]

100

120

140

160

(b) Tracking result of Task B, rrmse = 0.51 80

The authors acknowledge the Republic of Slovenia Ministry of Education, Science and Sport grant Motion Analysis and Synthesis in Human and Machine (P2-0228C). The authors would also like to thank both patients for participating in experimental training.

60 F [N]

40

REFERENCES

20 0 -20

1. 0

20

40

60

80 100 120 140 t [s] (c) Stimulation intensity (pulse width) during Task B

160

pw [ms]

30

2.

20

3.

10

0

0

20

40

60

80 t [s]

100

120

140

160

Fig. 4 Tracking of patient AD (a) Task A, (b) Task B, (c) output of the controller during Task B

4. 5.

Popovic MR, Thrasher TA, Zivanovic V at al. (2005) Neuroprosthesis for retraining reaching and grasping functions in severe hemiplegic patients. Neuromodulation 8:58–72 Hines AE, Crago PE, Billian C. (1995) Hand opening by electrical stimulation in patients with spastic hemiplegia. IEEE Trans Rehabil Eng 3:193–205 McPhee SD. (1987) Functional hand evaluations: a review. Am J Occup Ther 41:158–163 Kurillo G, Zupan A, Bajd T. (2004) Force tracking system for the assessment of grip force control in patients with neuromuscular diseases. Clin Biomech 19:1014–10221 Kurillo G, Gregoric M, Goljar N et al. (2005) Grip force tracking system for assessment and rehabilitation of hand function. Technol health care 13:137–149

IV. DISCUSSION AND CONCLUSION As it is evident from results, both patients gained strength in finger flexor and extensor muscles. Patient AD achieved steady improvement of maximal voluntary hand force in closing and opening throughout the training. Patient AS also achieved steady improvement of maximal voluntary force in hand opening, while maximal voluntary force

Author: Institute: Street: City: Country: Email:

Jernej Perdan Faculty of Electrical Engineering Tržaška 25 Ljubljana Slovenia [email protected]

__________________________________________ IFMBE Proceedings Vol. 16 ___________________________________________

New Experimental Results in Assessing and Rehabilitating the Upper Limb Function by Means of the Grip Force Tracking Method M.S. Poboroniuc1, R. Kamnik2, S. Ciprian1, Gh. Livint1, D. Lucache1 and T. Bajd2 1

Technical University of Iasi/Faculty of Electrical Engineering, Iasi, Romania University of Ljubljana/Faculty of Electrical Engineering, Ljubljana, Slovenia

2

Abstract— The aim of the paper is to present new experimental results while using a tracking system for the assessment and training of grip force control in patients with neuromuscular diseases. In conjunction with the Jebsen-Taylor hand test the Grip Force Tracking System proved to be a valuable tool to assess hand dexterity and to quantify the hand rehabilitation process in stroke patients. Keywords— grip strength, stroke, hand rehabilitation.

I. INTRODUCTION Stroke is a leading cause of serious, long-term disability. The World Health Organization estimates for the year 2001 that there were over 20.5 million strokes worldwide. 5.5 million of these were fatal [1]. Many stroke survivors have problems with thinking as well as with their physical disabilities. It has been estimated that 33% of stroke survivors need help caring for themselves, 20% need help walking, 70% cannot return to their previous jobs and 51% are unable to return to any type of work after stroke [2], [3]. According to the National Stroke Association: 10% of stroke survivors recover almost completely, 25% recover with minor impairments, 40% experience moderate to severe impairments that require special care, 10% require care in a nursing home or other long-term facility, 15% die shortly after the stroke and 14% (approximate) of stroke survivors experience a second stroke in the first year following a stroke [4]. 28% of people who suffer a stroke are under age 65 and a well established rehabilitative process may bring more of them back to work. The above enlisted data inspire the scientific and medical community to find the best rehabilitation methods to treat and assess the stroke patients during the post-stroke recovering process. Stroke affects different people in different ways, depending on the type of stroke, the area of the brain affected and the extent of the brain injury. Paralysis with weakness on one side of the body is a common after effect. Within the physical therapy, the rehabilitation process aims to help the patient to regain its ability to walk and the mobility of the affected upper limb as it was before the unwished event. Functional Electrical Stimulation (FES) has been proven to be an efficient method to improve walking in hemiplegia

[5]. Measures as walking speed and physiological cost index (PCI) over 10 m has been proven efficient in assessing the functionality improvements of the affected lower limb both with and without usage of the Odstock Dropped Foot Stimulator (ODFS),. Assessing the hand functionality and overall functionality of the upper limb is more difficult. Some tests assessing the range of motion & sensation, strength and dexterity have been proposed. The Jebsen-Taylor test has been proven to be an objective test of hand functions commonly used in activities of daily living [6]. The test items include a range of fine motor, weighted and non-weighted hand function activities which are sorted as: (1) writing (copying) a 24 letter sentence, (2) turning over 3 x 5” cards, (3) picking up small common objects such as a paper clip, bottle cap and coin (4) simulated feeding using a teaspoon and five kidney beans, (5) stacking checkers, (6) picking up large light objects (empty tin can) and (7) picking up large heavy objects (full tin can x 1 lb). Once the stroke patient regains some movement over the shoulder and elbow, hand dexterity and grip force have to be assessed. The O’Connor Finger Dexterity Test requires hand placement of 3 pins per hole. The test is designed as an eye-hand coordination test similar to the Minnesota Manual Dexterity test [7]. Some grip strength measurements are predominantly focused on the assessment of the maximal voluntary grip force, but it is important to assess the ability to control the grip strength of sub-maximal forces which are employed during grasping and manipulation of different objects. The Grip Force Tracking System (GFTS) has been developed as an assessment tool to evaluate effects of physical therapy or to train stroke patient’s grip force [8]. The GFTS involves biofeedback training methods and consists of two gripmeasuring devices of different shapes (cylinder and thin plate) which connect to a personal computer through an interface box. During the tracking task a person applies the grip force according to the visual feedback on the target signal while minimizing the difference between the target and the actual response. In the paper we present experimental results that have been obtained during the assessment and training of some incomplete spinal cord injured (SCI) or stroke (CVA) pa-

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 954–957, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

New Experimental Results in Assessing and Rehabilitating the Upper Limb Function by Means of the Grip Force Tracking Method

955

tients while performing hand exercises within the Rehabilitation Hospital of Iasi, Romania. The Jebsen-Taylor test as well as the Grip Force Tracking System based test have been performed. The aim of our study was to find out ways to increase the hand functionality recovery rate, and to identify if among the enlisted categories of patients there are some that can not benefit by using the GFTS system. II. MATERIAL AND METHODS A. Grip Force Tracking System The Grip Force Tracking System (GFTS) consists of two grip-measuring devices of different shapes (cylinder and thin plate). The cylindrical device allows assessment of grip forces up to 300 N with the accuracy of 0.02% over the entire measuring range. The second device is made up of two metal parts which shape into a thin plate at the front end being used to assess or train fingers pinch task. It can measure forces up to 360N with the accuracy of 0.1%. The output from the two grip-measuring devices is sampled through the interface box, consisting of an amplifier with supply voltage stabilizer and an integrated 12-bit A/D converter. The interface box connects to the parallel port of a personal computer, which is used for data acquisition and visual feedback. The tracking task as part of the biofeedback training involves the patient in tracking of an on-screen presented target by applying the appropriate grip force to the endobject of the grip-measuring device. The computer screen shows a blue ring that will modify its vertical position in accordance with a target signal. The voluntary applied grip force is related to a red spot which moves upwards when the force is applied to the measuring object and returned to its initial position when the grip is released. The aim of the tracking task is to continuously track the position of the blue ring by dynamically adapting the grip force.

Fig. 1 The SCI patient performing the (7)th Jebsen-Taylor hand test task Table 1 CVA patients Patients

P1 P2 P3 P4

Age [years] 58 60 65 41

Gender

Male Male Male Female

Time post stroke [months] 6 4 9 12

Affected side of the body Right Right Left Left

med consent. All the investigations have been accomplished at Rehabilitation Hospital of Iasi (Neurology Clinic) under the supervision of physicians and kinetotherapists. C. Data analysis

B. Participants One incomplete SCI patient (injury level: C5-C6, years post injury: 2, 45 years old, female) and four CVA patients (see Table 1) participated in the evaluation study of the Grip Force Tracking System. The SCI patient is able to sustain for short time a standing position between parallel bars and regularly performs arm exercises with 5 kg dumb bells while lying down on a bed. In this case the GFTS has been used as an assessment device to assess grip and pinch forces. The Jebsen-Taylor hand test provided data about the functionality of the upper limbs on a longer period (see Figure 1). Prior to the investigation, all subjects gave in for-

Each Jebsen-Taylor hand test task is timed to a maximum of 80 seconds. A number of five objects have to be moved while performing a test task (i.e. a number of five playing cards for the 2nd test item). The performance of the GFTS sinus task has been assessed by calculating the relative root mean square error (RRMSE) between the target force and the measured output force over the trial time [9]. The tracking error was normalized by the maximal value of the target signal to allow comparison among the results obtained in different grips and patients. A lower tracking error suggests better activation control of the corresponding muscles and improved hand functionality.

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III. RESULTS

10

8

Force [N]

The SCI patient started the usual kinetotherapy treatment after three months of the trauma. Only five months after the beginning of the treatment the patient has been able to coordinate the main movements of the upper limbs. It was the moment to start testing the arm functionality and some of the Jebsen-Taylor hand test items provided consistent data. An FES based rehabilitation treatment of the upper limbs that started after 12 months since the spinal cord trauma has been proven beneficial. The SCI patient has been able to perform all the Jebsen-Taylor hand test tasks, and over a three months period the time to perform each task decreased with 10÷15%. It was the moment when a training device as GFTS seems to bring more benefits while it improves the hand grip and finger movements. The patient remarked a better dexterity while tapping at the computer keyboard. The main difficulty with the treatment of CVA patients is the reduced time (three weeks) that they are allowed to be hospitalized during their rehabilitation period. They have to go back home and to continue with an ambulatory treatment, being able to be reassessed only after another few 4-5 weeks during a new hospitalization period. Therefore, the GFTS has been proven to be more effective as an assessment tool than a training tool. All the CVA patients have been assessed during their hospitalization when they are performing an usual kinetotherapy treatment. The discussion takes into account the first (beginning of the hospitalization) and the last assessment (end of hospitalization). The patient P1 (Figure 2) that performed the grip force sinus tracking test (lateral grip) showed a RRMSE=2.15 while the mean maximal force was 42.5 N.

Patient P1, Right hand, Lateral Grip (RRMSE=2.15)

12

6

4

2

0

0

10

20

30

40

50

60

time [s]

Fig. 3 Tracking results of

the P1 CVA patient

It is important to observe that the patient had difficulty with releasing the grip what made him difficult to reach the minimum picks of the sinus. Treatment of this patient did not showed relevant improvements in grip force or RRMSE after three weeks of rehabilitation period. For the same tasks the patient P3 achieved a RRMSE=0.85 with a mean maximal force of 28.5 N and the patient P4 achieved a RRMSE=1.5 with a mean maximal force of 26.3 N. For all these three patients we have

Patient P2, Right hand, Lateral Grip (RRMSE=0.71) 20

Force [N]

15

10

5

0 0

10

20

30

40

50

60

time [s]

Fig. 2 The P1 patient being assessed with the GFTS

Fig. 4 Tracking results of

the P2 CVA patient

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concluded that there is a need for another assessment after more than three weeks in order to obtain conclusive results. It is intended to assess them all once they will return for a new hospitalized rehabilitation treatment. It is interesting to remark that the patient P2 has achieved interesting results over a period of three weeks. The maximal force was in the range of 68÷70 N, and the RRMSE decreased from 1.2 to 0.85. The results suggest that treatment at time only 4 months after stroke is more beneficial and faster recovery can be achieved.

Republic of Slovenia Ministry of Education, Science and Sport. The work has been supported within the frame of the Slovene-Romanian Bilateral Scientific and Technological Cooperation Project: "Standing-up motion augmentation in paraplegia by means of FES and robot technology " and the Romanian grant CEEX24-I03/2005.

REFERENCES 1. 2.

IV. CONCLUSIONS In summary, the results of our tests in stroke patients show that there is a degree in which their grip force control is affected by the disease. The level depends from person to person. The Grip Force Tracking System proved to be a valuable tool to assess CVA patients and will be further used as a training tool. One observation that came from the physiotherapists suggests that GFTS wouldn’t be appropriate to be used in patients that elicit severe spasticity in the upper limb. That kind of patients usually elicit high grip forces but they are unable to release the grip. The physiotherapists suggested also that it will be interesting to use the GFTS in therapy on patients that recovers after a peripheral nerve lesion. The biofeedback associated with the performance of the tracking task can further assist the overall rehabilitation process by providing feedback on the progress to the patient.

ACKNOWLEDGMENT The authors gratefully acknowledge the financial support of the Romanian Ministry of Education and Research and

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3. 4. 5. 6. 7. 8. 9.

The Internet Stroke Center at http://www.strokecenter.org. Black-Schaffer RM, Osber JS (1990) Return to work after stroke: development of a predictive model. Arch Phys Med Rehab 71:285290. Stroke Awareness at http://www.strokeawareness.org. Stroke: Conventional Treatments for Stroke at http://www.holisticonline.com. Taylor, P.N., Burridge, J.H., Dunkerley, et al (1999). Patients perceptions of the Odstock Dropped Foot Stimulator (ODFS). Clinical Rehabilitation, 13:439-446. Jebsen, R.H., Taylor, N., Trieschmann, R.B., et al (1969). An objective and standardised test of hand function. Arch of Physical Medicine and Rehabilitation, 50(6):311-319. Dexterity tests: hand eye coordination tests, at http://www.rehaboutlet.com. Kurillo G, Zupan A and Bajd T (2004) Force tracking system for the assessment of grip force control in patients with neuromuscular diseases, Clinical Biomechanics 19:1014–1021. Jones R D (2000) Measurement of sensory-motor control performance capacities: tracking tasks. In: Bronzino, J.D. (Ed.), The Biomedical Engineering Handbook, second ed, vol. II. CRC Press, Boca Raton. Author: Marian Poboroniuc Institute: Street: City: Country: Email:

Technical University of Iasi 53 B-dul D. Mangeron Iasi Romania [email protected]

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The “IRIS Home” A. Zupan, R. Cugelj, F. Hocevar Institute for rehabilitation, Republic of Slovenia, Linhartova 51, Ljubljana, Slovenia Abstract— The article presents the IRIS Home. IRIS is an acronym for Independent Residing enabled by Intelligent Solutions. It is planned as a demonstration apartment located at the Institute for rehabilitation in Ljubljana. It will be fitted with the latest equipment, technical aids and rehabilitation technology. The aim of the IRIS home is demonstration, testing and application of contemporary technological solutions that compensate for the most diverse kinds of disabilities and thereby improve the quality of life of persons with disabilities and assure their optimal occupational, educational and social integration in society. Keywords— IRIS Home, persons with disabilities, rehabilitation technology

I. INTRODUCTION Through diverse rehabilitation programs we seek to ameliorate or eliminate the patient's disability and handicap. We use the medical, psychological, social and occupational rehabilitation methods. Our ultimate goal is to enable the patient to achieve optimal participation in his/ her social life and occupation. Technical aids and rehabilitation technology are essential means for improving the life situation of severely impaired individuals; by these means we can compensate significantly for these patients’ disabilities. This latter aspect of rehabilitation gains increasing importance with advances in rehabilitation techniques and technology based upon overall developments in the sciences from which they derive. IRIS is an acronym for Independent Residing enabled by Intelligent Solutions. The IRIS Home is planned as a demonstration apartment of approximately 90 m² to be located at the Institute for rehabilitation in Ljubljana. It will be fitted with the latest equipment, technical aids and technology that compensate for various forms of disability. This apartment will be designed to enable persons with diverse disabilities, along with the elderly, to attain maximum functional independence. The apartment will be equipped in a way that facilitates control over living space. It will be possible, for example, to activate powered windows, doors, blinds and heating system controls through different remote controls and systems that can be

activated by touch, voice commands and eye-pupil movement. The apartment will also be equipped with the latest communication technology adapted to diverse kinds of disability that allows the user to communicate outside the apartment in order to study, work and access entertainment. II. METHODS A. Project objectives • •

•

•

• •

Facilitate public access in Slovenia to the demonstration of contemporary technology that assists persons with diverse disabilities, as well as the elderly. Provide persons with disabilities and the elderly an opportunity in the demonstration apartment to try out and select technical solutions for their respective disabilities enabling maximum functional independence in a home environment. Advise patients and the elderly, along with their caregivers, on the most rational and economic adaptation of their current living quarters with regard to their particular needs. Provide equipment manufacturers and service providers in the field of rehabilitation technology opportunity to promote and test their solutions for various types of disability in the integrated environment of the demonstration apartment. Create possibilities for research and development in the fields of e-accessibility and e-inclusion in Slovenia. Facilitate activities for the promotion and application of a policy of e-accessibility in Slovenia.

B. Immediate goals • • • • •

Facilitate greater independence among all groups of users. Reduce the cost of home-care (health care, nursing and other forms of assistance). Improve the safety of the user. Reduce the need for re-location in retirement homes and other suitable institutions. Create modular solutions that can be applied in diverse user environments (private living quarters, social institutions, retirement homes, etc.).

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C. Users • • • •

•

Persons with different disabilities (with physical/mobility impairments, blind or sight impaired, with hearing impairments, as well as the elderly). Professional organizations will use the demonstration facility for training and planning diverse activities for the users: persons with different disabilities and the elderly. The general public who can be familiarized with the requirements of patients and the elderly and the technical solutions to their needs. Students of medicine, social services and technology who through training in this facility familiarize themselves with the needs and problems of diverse kinds of disability and with solutions to these problems. Designers of similar facilities, especially architects, interior designers and equippers responsible for the technical documentation of new housing and adaptation of existing housing to meet the needs and demands of IRIS users. III. RESULTS AND DISCUSSION

From the beginning this project has been planned and led to facilitate a “full life” for its users. It is our aim, through broad promotion of this demonstration apartment among the general public, to provide individuals and their families the possibility to see and experience technological solutions to the problems of persons with different disabilities and the elderly and to find solutions enabling greater quality of life among these persons. The IRIS Home will be integrated into regular rehabilitation programs for the most severely impaired patients. In this way we will be able to determine what practices and technological equipment can provide optimal solutions for independent and quality living in one’s home environment. Occupational therapists and technicians employed in the IRIS Home will demonstrate the use of various technical solutions and inform potential users (and their families) about the most cost effective and readily available solutions to their individually specific needs. The professionals mentioned above will also assist in the recommendation and adaptation of technology (installed in the IRIS Home) for use in the home environment of individual patients. In this way we will transfer rehabilitation from an institutionalized setting to patients’ home environments. By using visiting health personnel to conduct rehabilitation programs in

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the technologically well-equipped home environment of the individual patient we will attain a more complete and better adapted program of care. This approach represents a big advance in the way we conceive and practice rehabilitation. Rehabilitation will also be transferred from institutions to home environments using “telemedicine” and “telerehabilitation” programs. By promoting and using the most recent communication technologies it will be possible to monitor remotely the health status of patients and thereby assure greater security for the patient and reduce the costs of supervision, control and care of patients. It will also be possible to administer remotely certain elements of rehabilitation programs, most importantly, the counseling and teaching of patients. This will reduce transportation, visitation and care costs. The results of different studies regarding the use of smart technology for persons with different disabilities and the elderly showed that this kind of treatment improves the quality of the patient's life, enables his/her more independent living in home environment and that this kind of treatment is cost-benefit and costeffective (1-9). IV. CONCLUSION The IRIS Home represents a significant advance in Slovene rehabilitation medicine whereby we introduce a new field of activity – demonstration, testing and application of contemporary technological solutions that compensate for the most diverse kinds of disabilities and thereby improve the quality of life of persons with disabilities and assure their optimal occupational, educational and social integration in society. Rehabilitation will become centered in individual patients’ home environments but nevertheless incorporate effective connection and communication with those outside institutions upon which the patient depends. The work of the IRIS Home involves new expenditures: the employment of new professionals, maintenance of the demonstration apartment and its equipment and renewal and continual improvement of the same. Furthermore, it will be necessary to secure financing and support for technical aids and technological solutions for those citizens who require them to attain social equality and a better quality of life in their home environment. In spite of the initial high costs for this technology, in the long run this investment will reduce significantly public expenditures for the social and medical care of these persons.

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REFERENCES 1.

2. 3.

4. 5.

Magnusson L, Hanson E, Borg M. A literature review study of information and communication technology as a support for frail older people living at home and their family carers. Tehnol Disab 2004;16:223-235. Panek P. et al. 2001, Smart home applications for disabled persons – experiences and perspectives in Tang P, Venables T 2000, Smart homes and telecare for independent living. Andrich R. et al., The DAT Project: A Smart Home Environment for People with Disabilities. Proceedings: Computers Helping People with Special Needs, 10th International Conference, ICCHP 2006, Linz, Austria, July 11-13, 2006. http://www.hi.se/, http://www.hi.se/global/pdf/2002/02323.pdf. http://www.housing21.co.uk/pdf/pdf/Solutions%20autumn%202006.pdf .

6. 7. 8. 9.

http://www.telecareaware.com/2007/26/01/smart-living-for-peoplewith-dementia-in-bristol-uk/. http://www.tiresias.org/cost219ter/inclusive_future/(14).pdf. http://www.sentha.tu-berlin.de. http://www.dh.gov.uk/PublicationsAndStatistics/Publications/Publicat ionsPolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en ?CONTENT_ID=4081593&chk=eE9iLz. Author: Dr. Anton Zupan Institute: Street: City: Country: Email:

Institute for rehabilitation, Republic of Slovenia Linhartova 51 Ljubljana Slovenia [email protected]

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Use of rapid prototyping technology in comprehensive rehabilitation of a patient with congenital facial deformity or partial finger or hand amputation T. Maver1, H. Burger1, N. Ihan Hren2, A. Zuzek3, L. Butolin4, and J. Weingartner5 2

1 Institute for Rehabilitation, Centre for orthotics and prosthetics, Ljubljana, Slovenia University Medical Centre, Department of Maxilofacial and Oral Surgery, Ljubljana, Slovenia 3 IB-PROCADD d.o.o. Dunajska 106, Ljubljana, Slovenia 4 TECOS Slovenian tool and die development centre, Celje, Ljubljana, Slovenia 5 RTCZ Rapid prototyping and rapid tooling center, Hrastnik, Slovenia

Abstract—Our experiences show that patients wish to replace the lost part of their body with a prosthesis – epithesis that is a mirror image of the relevant healthy part of the body. Four years ago we linked up with other institutions, companies and the University of Ljubljana in order to search for new more advanced technological possibilities to bring the form of epitheses closer to the form of a healthy hand or part of a face. A healthy and impaired part of the body were scanned. A digital virtual model was made by using a computer programme. 3D printing technology, DMLS (Direct Metal Laser Sintering) and SLS (Select Laser Sintering) technology were used to build up the first model or mould for manufacturing a silicone epithesis. Through our development project we have found the way for the high-resolution digitising of body parts and technology to produce a prototype model and mould allowing the fine recognition of skin details. By using CAD-CAM high resolution technology, the highest-quality prosthetic design can be achieved even when the prosthetist lacks artistic skills. Keywords— prototyping

Epitheses,

Prostheses,

Digitising,

Rapid

I. INTRODUCTION At the Institute for Rehabilitation of the Republic of Slovenia we have been manufacturing and applying epitheses since 1993, by using silicone technology. Nowadays, this technology is based on manual shaping with which we strive to restore patient’s aesthetic appearance. Our experiences show that patients wish to replace the lost part of their body with a prosthesis that is a mirror image of the relevant healthy part of the body. Four years ago we linked up with other institutions and the University of Ljubljana in order to search for new more advanced technological possibilities to bring the form of epitheses closer to the form of a healthy hand or part of a face. Thus we started to develop an appropriate highresolution CAD-CAM system.

II. MATERIALS AND METHODS The development project covers three areas: • • •

a scanning system; positive model construction technology; and tool construction technology.

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A digital virtual model was made by using a computer programme. The healthy part of the body was treated and a mirror picture of the digitalised model was thereby obtained. This virtual digitalised model was then gradually adjusted to the model of impaired part of the body. The digitalised picture of the model was transferred into the STL database.

Scanning system During the development phase, three laser and optical scanners were tested in the making of a digitalized 3D model of a hand and stump. The following scanners were tested: freescanner CAPOD CAD-CAM system, Zscanner 700 and 3D optical scanner ATOS II 400. First, a healthy part of the body were scanned.

Later, a plaster model of the impaired part of the body that had previously been corrected was scanned.

Positive model construction technology

Mould construction technology 3D printing technology, SLS ( Select Laser Sintering) and DMLS (Direct Metal Laser Sintering) technology were used to build up the first model or mould. 3D printing technology was used to make a prototype model of the auricular epithesis.

Further, DMLS technology was used to make a tool for manufacturing a silicone finger epithesis.

At the last trial, SLS technology was used to produce a tool for manufacturing a silicone finger epithesis

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III. RESULTS With the assistance of experts from the companies participating in this project we tested and identified the devices and technological procedures that enable the manufacturing of epitheses. The best results when scanning were achieved by using the ATOS II photo scanner. When scanning directly on the body, there were some problems due to slight movements of the body. This was the reason for additionally scanning plaster models of the healthy as well as impaired parts of the body.

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to depend on the apparency of skin prints. The highest quality of the mould surface was achieved by the DMLS technology and the lowest by the 3D print technology, which produced a rougher surface of the prostheses test model despite the satisfactory apparency of the skin prints. The SLS technology was selected for mould manufacturing due to its accessible cost. The apparency of skin prints achieved by the SLS was not essentially lower than that achieved by the DMLS technology.This mould can be directly used to be filled with silicone material. IV. DISCUSSION During the development phase, CAD-CAM technology processes were defined to enable the production of silicone prostheses after partial hand amputation, which in their form mirror the patient’s healthy hand. Most centers for manufacturing silicone hand prostheses nowadays use the procedures of manual modeling [1, 2]. The quality of such prostheses depends on the artistic skills of the prosthetist. By using CAD-CAM high resolution technology, the highest-quality prosthetic design can be achieved even when the prosthetist lacks artistic skills. Such technology has been already used in designing and making of epitheses [3]. The same procedure is mentioned by Didrick [4], the author of an article on the manufacturing of finger prostheses. V. CONCLUSIONS

The picture of a virtual positive model shows all the skin details, including fingerprints. In this way the first part of the development project was completed. This virtual model helps to make a prototype model of an epithesis or mould in the STL database. The programme allows the adaptation of the digital model of the healthy part of the body, to the digital model of the stump or the impaired part of the face. The highest apparency of skin details in the mould was achieved by the DMLS technology (Direct Metal Laser Sintering) with 0.04mm accuracy. In the testing of the SLS (Select Laser Sintering) technology and the print technology, the accuracy was 0.1mm. When inspecting the moulds, the most accurate surface was found to be that produced by the DMLS technology. Silicone was poured into the moulds and after the vulcanization the quality of test prostheses was found

The final appeareance of the prosthesis depends greatly on its shape. Our experiences in using the CAD-CAM high resolution technology have shown that such technology enables computer-based manufacturing of prostheses, which in their form mirror the healthy hand.

By using CAD-CAM high resolution technology, the highest-quality prosthetic design can be achieved even when the prosthetist lacks artistic skills.

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REFERENCES 1. 2. 3. 4.

O'Farrell DA, Montella BJ, Bahor JL et. al. (1996) Long-term follow-up of 50 Duke silicone prosthetic fingers. J of Hand Surgery. 21B: 5: 696-700, 1996 Pilley MJ, Quinton DN.(1999) Digital prostheses for single finger amputations. J Hand Surg [Br]. Oct;24(5):539-41 Sykes LM, Parrott AM, Owen CP et.al. (2004) Application of rapid prototyping technology in maxillofacial prosthetics. Int. J Prosthodont. Jul-Aug;17(4);454-9. Didrick D at http://www.oandp.com/edge/issues/articles/200511_06.asp Author: Tomaz Maver Institute: Street: City: Country: Email:

Institute for rehabilitation Linhartova 51 Ljubljana Slovenia [email protected]

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Using computer vision in a rehabilitation method of a human hand J. Katrasnik1, M. Veber1 and P. Peer2 1

2

Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia

Abstract— We developed this program for the purpose of a rehabilitation method that requires a patient to move an object around with his hand. Using a black and white firewire camera the program determines the position and orientation of a black rectangle on a white plane. The user must enter the length and width of the rectangle before the start. With this information the position is determined even if a part of the rectangle is obscured by a user’s hand. The program works in real-time (15 to 20 frames per second). Keywords— computer vision

I. INTRODUCTION One of the major goals of rehabilitation is to make quantitative and qualitative improvements in daily activities in order to improve the quality of independent living. When parts of the brain have been impaired by trauma, incomplete spinal cord injuries and stroke, the functions that those parts of the brain had must be relearned. Relearning is aided by rehabilitation. Relearning is fastest when rehabilitation is done early and if the patient performs task oriented exercises [3]. By using virtual reality in rehabilitation task oriented exercises become more motivating and engaging than formal repetitive therapy. Another positive aspect of virtual reality is that it is programmable, which means that tasks can be adapted to the patient. When the patient advances, tasks can be made more difficult. Our motivation was to develop a cheap method for measuring position and orientation of an object and use that information in virtual reality exercises. Position and orientation can be measured with commercial products such as OPTOTRAK. The main drawback of using such products is their high price. For example OPTOTRAK costs approximately $150 000. If we could develop a system, that would use only a black and white firewire camera and a PC, this rehabilitation method would be a lot more accessible to the patients, which could then do rehabilitation at home. That would reduce resources needed for rehabilitation and increase the time a patient spends in rehabilitation. Our goal was to determine if the position and orientation of a black rectangle, with known dimensions, on a white plane could be accurately resolved with a computer vision system in real-time. The system must be able to find out the

position of the object even if it is partly obscured with the user’s hand. II. TOOLS AND METHODS A. Tools used In developing this system we used some computer vision algorithms already implement in OpenCV [1], an open source computer vision library for C++. We also used this library for capturing images from the camera, displaying images on the screen and saving images to disk. For writing, compiling and debugging the program we used Microsoft Visual Studio 2005. For capturing the scene we used a black and white firewire camera with resolution of 640x480 pixels. The computer used for processing was a PC running Microsoft Windows 2000. The rectangular object was made of wood and painted black. B. Image processing We captured the image from camera using OpenCV [1] functions. On the captured image, which can be seen in figure 1, we used the Canny edge detection algorithm, which is implemented in OpenCV [1]. In order to find the

Fig. 1 Captured image

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gles that the line segments form with the x axis and then we compared these angles with one another. If the difference between two angles was 90 ± 2 degrees, we calculated next parameters: • • • • •

Fig. 2 The result of Canny edge detection algorithm

Fig. 3 Straight lines detect with cvHoughLines2 rectangle in the picture we first needed to detect straight lines. We did this with a function cvHoughLines2 with the CV_HOUGH_PROBABILISTIC parameter that returns a sequence of line segments. This function is implemented in OpenCV [1]. These line segments can be seen in figure 3. They are drawn in different colors. Figure 2 shows the output of the Canny algorithm. The Hough transform, Canny edge detection algorithm and their effects are described in [2]. C. Finding the rectangle When we had the data of all of the line segments in the picture, we needed to analyze that data, in order to find the line segments that form a rectangle. We calculated the an-

the shortest distance between the ends of line segments length of both line segments the angle between the line segments the orientation of the angle that the line segments are forming the position of the vertex of this angle

We saved these parameters in a structure representing a right angle. If the orientation and the vertex in multiple angles were very close together we averaged these right angles. We averaged all the parameters, except the lengths of both line segments; instead we kept the longest lengths. The angles, with the shortest distance between the ends of line segments, longer than half of the longest line segment, could not be a part of a rectangle and were therefore eliminated. If two angles lie on the same line and their orientation is correct, they form a side of a rectangle. So we checked each ray of each angle, if on any of these rays lays a vertex of another angle. If there was another angle we compared the orientations. If the difference in orientations was ±90 degrees the two angles formed a side of a rectangle. Whether this side was the longer or the shorter one, we found out by comparing the length of the line segments. If the line segment lying on the ray, we were checking, was longer than the other line segment of the angle, then that side of the rectangle was the longer one. We only searched for the shorter sides of the rectangle, because the user would probably be touching the longer sides. One side of the rectangle and the information about the model is enough to calculate the position of the center and the orientation of the rectangle. Dimensions of the model were scaled to fit to the short side found by the algorithm. If two short sides were found we calculated the position and orientation with both of them and then averaged the results. III. RESULTS The system calculated the position and orientation of the rectangular object even if someone was holding it with his hand. The system could not detect the object if it was moving to fast, if it wasn’t parallel with the plane it was on and if the lighting was inadequate. The system works as fast as 15 to 20 frames per second. The output of the program can be seen in figure 4.

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have to follow it. The progress of the patient would be measured by calculating the mean square distance between the objects and the mean square difference in orientations of the objects in a certain amount of time. The faster the reference object would move around the screen the more difficult the exercise would be. The system would be a lot more useful if it worked in three dimensions. This application indicates that determining the position and orientation of a rectangular box in three dimensions could be done with algorithms similar to the ones used in our program. Each face of the rectangular box would have to be in different color and a color camera would be necessary.

REFERENCES Fig. 4 Rectangle detected by the system IV. DISCUSSION The system worked well, if the lighting was good and if the object wasn’t moving to fast. This could be improved with higher shutter speeds, which would also affect the sharpness and brightness of the image. This system could be used as a cheaper alternative to OPTOTRAK. Using this system a simple rehabilitation method could be easily developed. The display of the PC would show a reference object and the object in the patient’s hand. The patient would then have to move the object he is holding in the position indicated by the reference object. The reference object would move around the screen and the patient would

1. 2. 3.

OpenCV library at http://sourceforge.net/projects/opencvlibrary/ Russ J C (1995) The Image Processing Handbook. Boca Raton Sveistrup H (2004) Motor rehabilitation using virtual reality. Journal of NeuroEngineering and Rehabilitation 1:10 Author address: Author: Institute: Street: City: Country: Email:

Jaka Katrasnik University of Ljubljana, Faculty of Electrical Engineering Trzaska cesta 25 SI-1000 Ljubljana Slovenia [email protected]

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A Hierarchical SOM to Identify and Recognize Objects in Sequences of Stereo Images Giovanni Bertolini, Stefano Ramat, Member IEEE Dip. Informatica e Sistemistica, University of Pavia, Pavia, Italy Abstract— Identification and recognition of objects in digital images is a fundamental task in robotic vision. Here we propose an approach based on clustering of features extracted from HSV color space and depth, using a hierarchical self organizing map (HSOM). Binocular images are first preprocessed using a watershed algorithm; adjacent regions are then merged based on HSV similarities. For each region we compute a six element features vector: median depth (computed as disparity), median H, S, V values, and the X and Y coordinates of its centroid. These are the input to the HSOM network which is allowed to learn on the first image of a sequence. The trained network is then used to segment other images of the same scene. If, on the new image, the same neuron responds to regions that belong to the same object, the object is considered as recognized. The technique achieves good results, recognizing up to 82% of the objects. Keywords— Artificial vision, hierarchical SOM, binocular

I. INTRODUCTION Object identification and recognition plays a fundamental role in human interactions with the environment. Building artificial systems able to automatically understand images is one of the greatest challenges of robotic vision [1]. Image segmentation is the first important process in many vision tasks since it is responsible for dividing an image into homogeneous regions so that the merging of two adjacent regions would produce a non homogeneous region [2]. Humans often achieve recognition using semantic characteristics to group parts of complex objects; an approach that goes well beyond the homogeneity of a single feature of the pixels in the image. The algorithm described here represents a hybrid approach to image segmentation, but it can be broadly considered as belonging to the class of region merging processes. Once the sought objects are identified and correctly segmented, the problem of recognition is often formulated as that of finding a description suitable for comparing the objects across the different frames or for building models that the objects in subsequent images have to match [3]. The aim of this work is to present a way to process natural binocular images for distinguishing meaningful objects from the background and storing a description of these objects for

recognizing them in subsequent frames. This can be seen as a two step problem: segmentation and recognition. The key idea of our system is to store the description of the objects in terms of the rules learned for identifying them in the first image and then use these rules to segment the subsequent frames. This approach allows to combine segmentation and recognition. II. ALGORITHM OVERVIEW Despite the importance of segmentation and the great amount of literature on this topic, there is currently no optimal solution to it. The reasons for this lack are well explained by Fu and Mui in [4]: “the image segmentation problem is basically one of psychophysical perception and therefore not susceptible to a purely analytical solution”. Thus, we reasoned that trying to mimic some of the putative processing of the Central Nervous System (CNS) in building such psychophysical perception could provide interesting hints for solving the problem at hand. It is currently believed that the CNS processes information in retinal images through parallel neural pathways that build up a description of different features of the visual scene. Those can then be combined at a higher level to obtain the visual perception of the world as we see it [5]. Such processing allows the CNS to dynamically build different interpretations of the environment, varying the weights it assigns to the different features. The approach to segmentation described in this work combines information on color, edges and depth of the image, which are computed using independent algorithms, to build a first segmentation. The combined output of the above procedures is used to train a hierarchical self organizing map network that builds the final segmentation by merging the regions that it assigns to the same cluster. Using this approach the network also stores a distributed model of the observed world, which works as an “expected image” to be used in the analysis of the subsequent frames. Overall, the described processing allows to produce a segmentation while simultaneously recognizing the objects that are present in the observed scene. To acquire the binocular images, we developed a simple vision system using two commercial web-cams with aligned

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optical axes so that the two images differ only for a translation perpendicular to such axes. Since depth information is available only for the part of the visual scene that is visible in both images, we applied all the processing techniques described in the following only to such common region. III. EXTRACTION OF FEATURES We chose to combine color space information with that on edges derived from the gray scale version of the images, and with depth information derived from the comparison of each image pair acquired by the binocular camera system. As we reasoned that it could be profitable to imitate the CNS approach to processing visual information, the extraction of each one of these three features is performed by a different algorithm so that the overall algorithm could be run in parallel. A. HSV color space Although color is usually represented in terms of its intensity in red, green and blue wavelengths (RGB space), such coding may not be the most appropriate for image segmentation because, in such space, the distance between two colors does not resemble that perceived by humans [2]. RGB coding therefore does not allow to reliably establish the similarity between two colors, which may instead be a useful criterion for determining if two regions pertain to the same object in the scene. We therefore decided to transform the data in the HSV (Hue, Saturation, Value) color representation, which separates color and intensity information, making it especially efficient in representing similarities when non uniform illumination creates differences between pixels of the same surface. In HSV space color information is represented by the hue (the dominant wavelength in the spectral distribution) and the saturation (the purity of the color) while the value is the intensity. B. Edge detection and watershed Edges, which can be identified as discontinuities in the grey level of the pixels in the image, are detected using a Sobel filter applied to the grayscale image. The resulting gradient map is then used as the input of the watershed algorithm [6], which builds an over-segmented map. The output of this processing step is an early, raw segmentation of the image that will be the basis for all subsequent elaborations. It is therefore important to not to oversee any boundary between regions, although this may lead to an oversegmented output. For this reason, the watershed algorithm, which intrinsically produces an over-segmentation since it

returns all the boundaries as having all the same ‘height’, appeared to be a good approach to this task. C. Depth estimate The knowledge of the distance of every point in the image from the cameras could provide valuable additional information in the image analysis process and in identifying the objects in the scene. The problem faced by the algorithms that compute depth from visual information (stereo vision algorithms), is that they need to know the correspondences between the pixels of the two images, i.e. the two projections needed for 3D reconstruction. A stereo vision algorithm outputs a map of the size of the common region discussed in section 2. In this map each element represents a disparity value, that is the difference between the position of two corresponding pixels in the two images: the larger the disparity, the closer the object is to the cameras. Based on a recent work by Di Stefano and colleagues [7] the proposed an algorithm attempts to estimate the disparity of a point in the reference image based on computing the sum of the absolute difference (SAD), in gray level, between a square window centered in the pixel of interest (the reference window) and an equal sized window (the sliding window) sliding on the corresponding scan line of the other image (the search image). In addition, following the suggestions in [8], we developed a multiple windows approach combining information over areas larger than the single window, which allows us to determine the matching pixel with greater confidence. To estimate the uniqueness of each match, besides the tests of sharpness and distinctiveness suggested in [7], we used the following additional criterion. For each scan line in the reference image we apply an iterative procedure that finds the collisions (multiple matches, i.e. groups of pixels of one image that correspond to the same pixel of the other image), keeps only the pair of pixels with the best SAD value and replaces the “loosing” matches with their succesive candidate within a subset of its best four solutions. This step can be seen as implementing a global constraint over each row of pixels, yet it is applied only to a subset of locally established matches. Two more procedures scan the resulting disparity map to remove non reliable matches pertaining to low texture areas and fill missing matches caused by occlusions. D. Merging of regions To perform a first merging of the small regions generated by the watershed we implemented a slightly modified version of an algorithm [9] that merges adjacent regions based on a local measure combining the difference in color

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A Hierarchical SOM to Identify and Recognize Objects in Sequences of Stereo Images

and the mean intensity of the edges that separate two regions. At each step the variance of the gray level within the new region is calculated and a threshold on variance is computed from the merging history of the region itself. Such threshold is then used to decide when to exclude a region from the merging. In the original algorithm [9] the color difference is measured as the distance between hue levels and is combined with edge intensity, weighing them respectively 80% and 20%. However, the HSV color space has some singularities that make the hue level less reliable as the saturation diminishes [2]. To avoid such pitfall, we chose to use an adaptive algorithm for selecting the weights of the two components of the similarity measure. Before beginning the merging process we subtract the background (the pixels that lie further than a chosen depth threshold). This forces the algorithm to consider the background as a single element, speeding up the merging. The resulting region map is made up of regions that represent homogenous and possibly meaningful parts of the objects in the scene. Each identified region is then summarized as a six values feature array containing the coordinates of its centroid and the median of each of the four computed features: hue, saturation, value and disparity. These feature arrays represent the input to the HSOM network, which produces the final output of the recognition process. IV. HSOM NEURAL NETWORK The Self Organizing Map [10] belongs to the class of unsupervised learning neural networks. SOMs are basically a clustering tool, able to build a map of the distributions of the input data, grouping them in clusters topologically ordered within the SOM structure. SOMs are a popular choice for clustering problems in image segmentation, which can be seen as a clustering process where each cluster encloses the portion of the feature space that represents an homogeneous region. On the other hand one of the main shortcomings of SOMs in our context is that they need the user to define the number of neural units before the segmentation begins, because it affects the number of regions in the result, which is a priori unknown. In our work we make use of a Hierarchical Self Organizing Map, an evolution of the classical SOM that tries to overcome the aforementioned shortcoming by building a hierarchical structure in which each layer is a single layer SOM. The main idea is that it is possible to segment an image by grouping its features at different levels of analysis, supposing that each layer of the HSOM could achieve a viewpoint from a different scale [11]. This could be very useful in an object identification task since it allows to

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gradually group the elements composing the objects without a priori defining the homogeneity criterion. Moreover this hierarchical structure grows during the segmentation process, thus partially overcoming the limit imposed by the fixed number of neurons of the classical SOMs. The inputs to the first layer of the network are the sixelements feature vectors characterizing each identified region. The first four are the median of the H, S and V component of the HSV color representation and of the depth over the pixels of each region, while the last two are the X and Y coordinates of the centroids of the region. Thus, half of the feature space takes in account the color descriptions, while the other half represents the position of the regions in 3D space. The size of each SOM layer is NxN where N depends upon the number n of input vectors (i.e. the number of regions for the first layer) through the formula:

N = 0.8 ∗ n

(1)

One of the main drawbacks of this approach is that it doesn’t take into account the size of the regions in building clusters. This could lead to errors in cluster formation, because small regions are usually less reliable then the bigger ones. To enhance the role of large regions we increase the number of times that their vectors are presented to the HSOM based upon their area. Once the first layer is trained, the weight vectors of each neuron that won for at least one input become the input vector for the second layer. The size of the second layer is also determined using Eq. 1, where n is now the number of winning neurons in the first layer. Thus, the network grows dynamically, adding new layers until the desired size of a 3x3 neurons layer is reached. The choice of nine neurons in the final layer, allowing to recognize up to nine different objects, is empirical and depends on the structure of our images, which usually contained at most three objects. At the end of this process the trained network has learned a description of the visual scene that can be used to recognize the same objects in other frames of the same scene. V. EXPERIMENTAL RESULTS Following the idea suggested by Smith et al. [12] we can consider an object shown in different images as recognized if it is correctly labeled in all the images and if its position in the different images is correctly estimated. We therefore decided to evaluate the whole system only in terms of its object recognition performance, which is the overall goal of the approach proposed here. To this goal, we acquired sequences of stereo images of a fixed visual scene while moving the binocular system along

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a straight line perpendicular to the optic axes of the cameras of a predetermined amount between two frames. Therefore, when an object is detected in one image, the estimate of its position in another image in the sequence can be easily computed. Such estimate is used for evaluating the correctness of the position of the recognized objects, and for modifying the weights of the neurons to move them according to the information on the displacement of the cameras. Our “recognition test” can be summarized as follows: 1. Train the HSOM with one image of the sequence 2. Modify the coordinates stored as network weights using the information about the displacement of the cameras 3. Use the trained network for the segmentation of another image of the sequence, identifing the main region generated by each neuron in each image 4. Compute a dissimilarity measure (Eq. 2) between each possible pair of regions belonging to the two images 5. Match each region in the training image with the region having the lowest dissimilarity measure in the test image 6. Consider as recognized only those regions of the training image that match regions of the test image identified by the same neuron and having a dissimilarity measure I below a predefined threshold We repeated this procedure by training the network on each image in the sequence and testing the trained network on all the other images in the sequence. The dissimilarity measure I is made out of two parts that consider the variation of the area and the error in the centroid position, respectively. The formula can be written as I=

Area(Ri ) − Area(R' j ) Area(Ri )

+

Centroide (Ri ) − Centroid(R' j ) Centroide (Ri ) − Centroid(Ri )

(2)

where R represents regions in the training image and R’ regions in the test image; i and j represent the i-th and j-th neuron of the network, respectively, while the subscript e refers to the expected centroid position based on camera motion information. We consider that an object represented by Ri is recognized if the minimum of I is less than 2 and is obtained for j=i. The recognition performance is then evaluated as the percentage of recognized objects over the total number of expected objects (based on the number identified in the training image), and in terms of the mean error in area and in centroid position. We tested our system over three sequences of six binocular images each; two sequence showing three objects in the foreground while the other only two. Due to the arrangement of our binocular system the foreground is defined as the portion of the observed scene lying between 50 cm and 150 cm from the cameras. Altogether we tested our system over a total of 18 training images, 90 test images and 240

Fig. 1 Images 1, 2 and 5 of the 2nd sequence (a,b,c) and the respective output of the algorithm (d,e,f). Each color represent a label, i.e. an object. The network is trained only on the first image (a).

objects that had to be recognized. The system recognized 82% of the objects, with an average error of 14% in terms of area and of 25% in the position of the centroids. VI. CONCLUSIONS We developed a binocular vision system for detecting unknown objects in the foreground of the visual scene and recognize them in other views of the same scene. This is achieved using a HSOM network combining information from color space, edges and depth derived by independent algorithms. The HSOM shows good clustering ability, almost always correctly grouping the regions that compose the objects. The information stored in the network allows recognition of the same objects in the other frames of the sequence. Thus, the network weights represent an “expected image”, helping both segmentation and recognition. Our preliminary results appear to be very promising. Future developments of this work will consider continuously adjusting the description of the scene moving the HSOM neurons by partially retraining the network on each new image pair, and using camera motion information provided by inertial sensors. The ultimate goal will be that of being able to detect and track unknown objects in an unconstrained environment.

REFERENCES 1. 2. 3. 4. 5. 6.

Kragic D, Björkman M, Christensen H, Eklundh J (2005) Vision for robotic object manipulation in domestic settings. Robotics and autonomous Systems 52:85-100 Cheng HD, Jang X, Sun Y, Wang J (2001) Color image segmentation: advances and prospects. Pattern Recognition 34:2259-2281 Roy SD, Chaudhury S, Banerjee S (2004) Active recognition trought next view planning: a survey. Pattern Recognition 374:429-446. Fu KS, Mui JK (1981) A survey on image segmentation. Pattern Recognition 13:3-16. Kandel ER, Schwartz JH, Jessel TM (1999) Principles of Neuroscience. Elsevier Beucher S (1992) The watershed trasformation. Scanning Microscopy

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Di Stefano L, Marchionni M, Mattoccia S, Neri G (2004) A fast areabased stereo matching algorithm. Image and Vision Computing 22: 983-1005 Hirshmüller H (2002) Real-time correlation-based stereo vision with reduced border errors. International Journal of Computer Vision 47:229-246 Navon E, Miller O, Averbuch A (2005) Color image segmentation based on adaptive local tresholds. Image and Vision Computing 23:69-85

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10. Kohonen T (1982) Self-organized formation of topologically corrected feature maps. Biological Cybernetics 43:59-69 11. Bhandarkar SM, Koh J, Suk M (1997) Multiscale image segmentation using a hierarchical self-organizing map.Neurocomputing 14:241-272 12. Smith K, Gatica-Perez D, Odobez JM, Ba S (2005) Evaluating MultiObject Tracking,.IEEE conference on computer vision and pattern recognition

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A model arm for testing motor control theories on corrective movements during reaching D. Curone, F. Lunghi, G. Magenes and S. Ramat Dip. Informatica e Sistemistica, Università degli Studi di Pavia, Pavia, Italy Abstract— Based on a simple robotic toolkit, we have developed a robotic arm control system to be used as a humanoid benchmark for testing trajectory planning models and control hypotheses for both reaching and corrective movements during reaching. The developed system integrates visual sensory feedback of the end-effector of the arm allowing controlling its movement online. The system may operate in 1) open-loop configuration providing the servos at the joints of the robot one point of an initially planned trajectory every 20 ms; 2) correction closed loop configuration using visual feedback only for planning the corrective movement trajectory or 3) continuous closed loop configuration using initial conditions derived from visual feedback information and computing the next trajectory point at every time step. Although the planning and control of reaching movements has been extensively investigated, not much is know on the planning of corrective movements. The research tool we developed will be used to implement and test different trajectory planning and movement control models. Keywords— Anthropomorphic robotics, movement planning, biomimetic artifacts

I. INTRODUCTION When planning a movement the central nervous system (CNS) has therefore a redundant number of DOF and the problem of determining the joint angles to take the end effector to the target is thus ill-posed. Also, the CNS may choose any one trajectory (determining hand position as a function of time) among the infinite possible trajectories that would allow to reach the intended target. The same occurs if the movement is to be performed on a planar surface, reducing the dimensionality of the space to two. Yet, experimental results have shown that planar reaching movements are characterized by a number of invariants that are common to all normal subjects, e.g. the quasi-linearity of the trajectory of the end-effector (the hand) and the unimodal, bell-shaped velocity profile of the hand [1]. Many studies have thus faced the ‘reverse engineering’ problem of understanding which principles may govern the selection of the trajectory to be carried out. It is generally accepted that the CNS plans the trajectory based on an optimization principle, that is, it determines the trajectory that minimizes some cost function. Different proposed models can be found

in the scientific literature that are able to produce reasonably human-like trajectories as the minimum jerk model [2] and minimum torque-change model [3]. These models can and have been used to plan the movement trajectories of humanoid robots both because they allow to produce humanlike behavior, and for their intrinsic ability to reduce the stress on the actuators by producing smooth movements. On the other hand, reaching movements are not ballistic movements that are preprogrammed and carried out in an open-loop context, without the possibility to intervene on the planned trajectory to modify it. A number of studies have proved the ability of the CNS to correct the planned trajectory following a target jump during pointing and reaching movements [4-6]. Moreover, recent studies [7] have highlighted the ability of the CNS to make online trajectory corrections when a visible target is displaced, even unconsciously, at the beginning of the reaching movement. An interesting question is therefore that of understanding how the hand trajectories are modified online when the intended target is displaced or follows an unpredictable motion pattern. Does the CNS compute a new trajectory using an optimization model with new initial conditions imposed by the ongoing movement, or is the correction controlled through different mechanisms? An important advantage of model-based representations is that they offer the possibility to be implemented and tested and thus provide a benchmark for the theories and hypotheses they rely upon. One constraint imposed on any humanoid model to be used for studying motor responses to target displacements is that of the reaction times of humans. Experimental findings have shown that humans can respond to visual target displacements within about 110 ms [5;6] and that they are able to correct the direction of the trajectory in about 250 ms [8;9]. Our goal in the work described here was that of building one such benchmark model to be able to test motor control theories on reaching movements through the reproduction of real experimental conditions. The following describes our software and hardware implementation of a three DOF robotic arm control system integrating online visual sensory information on target and hand location. Initially we implemented motor planning based either on the minimum jerk [2] or on the minimum variance model [10], both for preprogramming and for online correction of the end effec-

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 986–989, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

A model arm for testing motor control theories on corrective movements during reaching

tor trajectory. For completing this task we employed very limited economic resources, which represented our cost function in this context.

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of the LED mounted on the end-effector tip. These are acquired through two analog input lines of the PCI 6224 card. The overall system is pictured in Figure 1. B. Software control

II. MATERIALS AND METHODS A. Hardware The toolkit we used was a Lynx6 (Lynxmotion, Inc.) five DOF robotic arm. The three degrees of freedom of the arm that were exploited in this project are actuated by four Hitec HS475 servo motors, two moving the shoulder, and one each for the elbow and wrist joints. The robotic arm has an arm length of 12.0 cm, a fore arm of 12.0 cm and a hand of 4.7 cm. The servos are controlled in position using a PWM code with pulse cycle of 20 ms and a range of pulse duration between 0.5 and 2.5 ms. The angular excursion of each servo is of about 200 deg, thus a discretization of the 2 ms maximum pulse duration in 1000 steps of 2 μs each, yields angular increments of 0.2 deg, which allow for a good accuracy in determining the angular positions of each servo and thus of the position of the hand in space. The angular velocity of each joint is therefore controlled by modulating the increments of pulse duration that are sent to the servos every 20 ms. The minimum velocity for each servo is therefore 0.2 deg in 20 ms, or 10 deg/s. To cope with the timing requirements imposed by the experimental results, we chose to avoid the controller provided with the modeling kit and decided to directly drive the motors through the digital output lines of a National Instruments PCI 6224 card. The ‘visual’ sensory feedback is provided by a infra-red (IR) camera system with its controller hardware, model Hamamatsu PHS controller C2399, that provides the X and Y planar coordinates of a IR emitter (typically a IR LED) in its workspace. The controller outputs two voltages (range 5V to +5V) that are proportional to the X and Y coordinates

Y X

A Figure 1 A.

B

overview of the complete system with the IR camera providing the visual feedback on hand position. B: detailed view of the robotic arm.

In order to meet the timing requirements imposed by the need to be able to close the loop of the control system and intervene on the servo commands to correct the overall endeffector trajectory we have developed a custom software architecture comprising three subsystems: •

•

•

A Matlab interface allowing to set the movement parameters (2 DOF or 3 DOF, target position, timing, etc.) and to graphically visualize the performance of the system by comparing it to the ideal trajectory. A C++ ActiveX server providing the procedures for planning the end-effector trajectory. The higher computational efficiency of this language allowed us to develop a component that permits to close the arm control loop. It is able to use feedback sensory data (currently vision only) in planning the new position of the endeffector, determine the corresponding joint positions, compute and send the new command to the servos within the 20 ms interval between one command and the following one. A LabView dynamic link library (dll) component that is invoked by the ActiveX module and interacts with the PCI 6224 card.

C. Software architecture Overall, the user interacts with the Matlab program, sets the parameters of the desired trajectory and defines, if needed, where and when the target will be displaced within the working area, and the operating mode of the control: open loop, correction closed loop or closed loop. In the first mode the planned trajectory is sent, one command every 20 ms, to the servos without considering the visual feedback of hand position. In correction closed loop mode, instead, the visual feedback provides information on the ongoing movement only when a displacement of the target is perceived. Then, a new trajectory is planned based on the new target position and on the initial conditions determined by the ongoing movement. In continuous closed loop mode, the visual feedback information is used together with target position to compute a new trajectory at each 20 ms step. The trajectory is then planned in Cartesian coordinates using either the minimum jerk model or the minimum variance model implemented in the ActiveX control. The general solution of the minimum jerk model implemented in the ActiveX component is therefore (for each movement dimension):

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v a0 2 l 3a t + (10 3 − 6 02 − 0 )t 3 + ... 2 2d d d v0 3 a0 4 v l l 1 a0 5 + (−15 4 + 8 3 + )t + (6 5 − 3 04 − )t 2 d2 2 d3 d d d d x(t ) = v0t +

(1)

Where d is the movement duration, l is the distance to the target, v0 is the initial velocity, a0 the initial acceleration. The final velocity and acceleration are always set to zero. For planning the correction allowing to reach the displaced target, v0 and a0 are computed based on the visual feedback. This is accomplished using the current sample and one or two previous data points for computing the average velocity and acceleration, respectively. At each step, the following position to be reached is then transformed into joint coordinates through an inverse kinematic model. Whilst for the two DOF configuration we have implemented the analytical solution (Cartesian coordinates are univocally mapped on the two joint coordinates of the arm), for the three DOF configuration the inverse kinematic problem is solved using a multilayer neural network (MLP) previously trained offline. The target joint configurations used for the training of the MLP were obtained through numerical optimization procedures. This step therefore determines the angular positions of the servos allowing to reach the following planned position. The desired position of each joint is coded in the 1 to 1000 scale of the servos and sent, every 20 ms, to the LabView dll which encodes them in terms of duration of the square wave controlling the servos. III. RESULTS When facing a target displacement, the described system allows to compute and send the commands for correcting the trajectory within two sampling intervals (40 ms) which is much

Figure 2.

Planned and recorded minimum jerk trajectories for a 19.7 cm diagonal movement on the XY plane. Open loop. Top panel: end-effector position traces. Bottom panel: velocity traces.

shorter than the reaction times reported in the literature [4;7]. Therefore the timing performance of the system is more than sufficient to reproduce realistically the features of human movements in terms of response times to perturbations of the experimental conditions. Thus, to reproduce the timing aspects of the different experimental conditions, we have added a further parameter that specifies the latency of the correction of the arm commands. Open loop mode. The planned minimum jerk trajectory and the recorded one for a diagonal movement on the XY plane are shown in Figure 2. The arm moves from point (0,10) to the target in (18,18) with a diagonal movement of amplitude 19.7 cm. We chose to plan the movement in order to accomplish it in one second. The data shows how accurately the end-effector follows the planned trajectory resulting in a mean squared error over the whole movement of 0.07 and 0.03 cm along the X and Y axis, respectively. Correction closed loop mode. Figure 3 shows the planned and the recorded trajectory of a reaching movement during which the target is displaced 8 cm to the right after 600 ms from movement onset. The initially planned trajectory had only an X component to move the end-effector from its starting point (0,10) to the target’s initial position in (0,18). The target displacement to the right causes the system to plan a new Y component, also following the minimum jerk model, that begins after about 720 ms and brings the endeffector on target. The mean squared error between the performed and the planned movement was of 0.03 cm on the X trajectory and 0.09 cm on the Y trajectory. Finally, Figure 4 shows the behavior of the end-effector during a movement in which the target is displaced further along the same direction of the initially planned trajectory.

Figure 3. Planned and recorded trajectory for a reaching movement with lateral target displacement. The movement stets off to reach a straight ahead target, which jumped 8 cm to the right 600 ms after the onset of the trial. Top panel: end-effector position traces. Bottom panel: velocity traces.

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the minimum variance model, although we plan to integrate further models in the system. The continuous closed loop configuration of the control system allows to reprogram a new trajectory considering the real hand position at every time step and thus implement and evaluate the performance of a next-state planner control [11;12]. Overall, the proposed solution represents a valuable tool for evaluating motor control hypotheses by allowing to easily reproduce the experimental conditions that are found in the literature.

REFERENCES 1.

Figure 4.

Position (top) and velocity (bottom) traces from a reaching trial during which the target is displaced in depth with respect to the original position. Mse was 0.04 for the X axis component and 0.02 for the Y axis.

The movement is therefore prolonged and the minimum jerk trajectory yields a velocity profile that shows an acceleration of the end-effector corresponding to the movement correction. The corrected movement lasted 200 ms longer than planned for the initial target. IV. DISCUSSION The prototype system presented in this work represents our attempt at developing a cheap humanoid robotic model that can be used as a benchmark for testing motor control hypotheses on reaching movements. The system implements a three DOF robotic arm based on a cheap commercial kit using servos for radio controlled models. Of the original kit, only the hardware of the arm was used in our prototype system, while the control software and hardware were custom developed for this project. The system was coupled to an IR camera system able to output the planar coordinates of a IR LED which was mounted on the arm end-effector in order to provide a ‘visual’ feedback of hand position that is used to control the movement online. Specifically, the system uses the fed back hand position to estimate its instantaneous velocity and acceleration (computed as a mean over the most recent data samples). This information is in turn used to provide the initial conditions for programming corrective movements following unexpected target displacements or for continuous closed loop control. Currently, both the initial and the corrective movement trajectories are planned based on the minimum jerk or on

Morasso, P., "Spatial control of arm movements" Exp.Brain Res., vol. 42, no. 2, pp. 223-227, 1981. 2. Flash, T. and Hogan, N., "The coordination of arm movements: an experimentally confirmed mathematical model," J.Neurosci., vol. 5, no. 7, pp. 1688-1703, July1985. 3. Uno, Y., Kawato, M., and Suzuki, R., "Formation and control of optimal trajectory in human multijoint arm movement. Minimum torque-change model," Biol.Cybern., vol. 61, no. 2, pp. 89-101, 1989. 4. Soechting, J. F. and Lacquaniti, F., "Modification of trajectory of a pointing movement in response to a change in target location," J.Neurophysiol., vol. 49, no. 2, pp. 548-564, Feb.1983. 5. Brenner, E. and Smeets, J. B., "Fast Responses of the Human Hand to Changes in Target Position," J.Mot.Behav., vol. 29, no. 4, pp. 297310, Dec.1997. 6. Paulignan, Y., MacKenzie, C., Marteniuk, R., and Jeannerod, M., "Selective perturbation of visual input during prehension movements. 1. The effects of changing object position," Exp.Brain Res., vol. 83, no. 3, pp. 502-512, 1991. 7. Sarlegna, F., Blouin, J., Bresciani, J. P., Bourdin, C., Vercher, J. L., and Gauthier, G. M., "Target and hand position information in the online control of goal-directed arm movements," Exp.Brain Res., vol. 151, no. 4, pp. 524-535, Aug.2003. 8. van Sonderen, J. F., Denier van der Gon JJ, and Gielen, C. C., "Conditions determining early modification of motor programmes in response to changes in target location," Exp.Brain Res., vol. 71, no. 2, pp. 320-328, 1988. 9. Castiello, U., Paulignan, Y., and Jeannerod, M., "Temporal dissociation of motor responses and subjective awareness. A study in normal subjects," Brain, vol. 114 ( Pt 6) pp. 2639-2655, Dec.1991. 10. Harris, M., and Wolpert, D., "Signal-dependent noise determines motor planning," Nature, vol. 394, pp. 780.784, Aug. 1998. 11. Hoff, B. and Arbib, M. A., "Models of Trajectory Formation and Temporal Interaction of Reach and Grasp," J.Mot.Behav., vol. 25, no. 3, pp. 175-192, Sept.1993. 1. Shadmeher, R. and Wise, S. P., The computational neurobiology of reaching and pointing Cambridge: MIT Press, 2005. Author: Stefano Ramat Institute: Dip. Informatica e Sistemistica. Università degli Studi di Pavia Street: Via Ferrata, 1 City: Pavia Country: Italy

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Assessment of hand kinematics and its control in dexterous manipulation M. Veber1, T. Bajd1 and M. Munih1 University of Ljubljana/Faculty of Electrical Engineering, Ljubljana, Slovenia Abstract— The aim of our work was to design a method for assessment and training of human hand dexterity while manipulating an object. A virtual environment was used to display a target object in various poses. The target poses were first recorded for a single person – a virtual trainer. The poses of a real object, held by the subjects included in the investigation, were assessed by a motion tracking device and displayed within the virtual environment. The subjects were asked to align the 3D images of real object and the target object. The target poses were normalized with respect to the different sizes of arms and hands. In this way all subjects were able to reach the desired target postures. Satisfactory repeatability of hand movements was observed in a single subject and across a group of twelve unimpaired subjects. Keywords— Human hand, Dexterity Assessment, Training, Rehabilitation, Virtual environment

I. INTRODUCTION The human hand is controlled at the central nervous system level [1], where visual and proprioceptive information is processed into a motor action, and also at the peripheral level, where motion is further determined by biomechanical constraints [2]. From the kinematic point of view there are at least two problems which have to be solved in order to perform a motion of forearm, wrist, and fingers [3]. The first one deals with the selection of a proper trajectory among an infinite number of possible trajectories from the starting to the final hand posture. The second problem is related to the transformation of hand pose into the angles of individual wrist and finger joints. In the studies of human prehension the solution of both tasks is frequently referred to as an optimal hand control [4]. The hand transport and preshaping phases of prehension have already been extensively studied [4, 5, 6]. In contrast to many studies related to the first two phases of prehension, the hand kinematics during the manipulation of a grasped object is not extensively described in the literature. The fact that there is still missing an appropriate method for assessment of hand and finger kinematics might be a possible reason for the dexterous manipulation phase of prehension not receiving the deserved attention. The aim of this paper is to present a virtual environment (VE) system for assessment and training of manipulation performed by fingertips, hand, and forearm. The proposed

approach employs optical tracking system to assess the poses of hand and arm segments while only collective activity of fingers is acquired. The method enables training of different poses of a target object displayed within VE by the help of a virtual trainer and normalization of the poses so that they can be reached by hands and arms of different sizes. II. METHODS A. Description of the system The experiment setup aimed for assessment of hand kinematics and motion of the object consists of the optical tracking system (Optotrak® Northern Digital Inc.) and ergonomically designed brace firmly attached to a desk as shown in Figure 1. The brace is designed to prevent elbow flexion-extension while allowing free pronation-supination of the forearm. The wrist and the fingers, which predominantly influence dexterity of the hand, are free to move within their range of motion. The angle between forearm and the desk is adjusted to approximately 40°. Elbow flexion is kept fixed at approximately 55°. Infrared markers are attached to the hand and the object to assess the motion of hand and object. Three infrared markers are placed on the brace representing the reference frame. The other markers are placed on anatomical land-

Fig. 1 The right arm supported by a custom designed brace

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Assessment of hand kinematics and its control in dexterous manipulation

marks established by palpation. One marker is attached to the elbow (olecranon), two are placed on the forearm (ulnar and radial styloid process), one is fixed to the wrist (capitate bone), and two markers are attached to the dorsal aspect of the hand (end of 2nd and 4th metacarpals). Six markers are placed on the prismatic object to ensure that at least three markers are visible in every reachable pose. Threedimensional (3D) positions of markers measured by the camera system are sent via local area network to the client computer for processing and visualization. A virtual reality library Maverik is used to develop the VE. The real object is displayed within the VE with opaque color. At the same time a semi-transparent target object with bright colored vertices is shown on the screen. The goal of the task is accomplished when the real object displayed within the VE is moved inside the target object. A new pose of the target object is shown when deviations of position and rotation are reduced below threshold values of required accuracy. At that time the color of the displayed real object changes to indicate matching of pose of both objects. The target poses shown in Figure 2 are chosen based on the poses of objects encountered in different daily activities such as holding a glass (Figure 2b), fastening a light bulb (Figure 2c) or throwing an object (Figure 2d). The initial pose, which is displayed at the beginning of each trial, is shown in Figure 2a. Once the initial pose is reached, the first target pose is displayed. When the real object coincides with the target object, the subject is instructed to bring the virtual object back to the initial pose. The described sequence is repeated for all target poses of the object. Prior to the tests, subjects are allowed to practice to get accustomed to the task presented in the VE. The display of virtual objects is additionally improved by adding texture gradient and linear perspective. The scale of VE is also equalized with the scale in the real world. Shallow holes are drilled

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into the surface of real object to ensure repeatability of position of fingertip contacts for different trials and subjects. The proposed system is aimed for the training and evaluation of hand dexterity in patients with neuro-muscular diseases. A patient with impaired hand is prone to compensate the reduced functionality by using the healthy hand or by moving the whole arm instead of using wrist and fingertips. The constraint imposed by the brace forces the patient to practice dexterous hand manipulation. However, as the motion of the whole arm is prevented, some target poses of the object might not be reached by arms and hands of different sizes. For this reason an adaptation of target poses is implemented. B. Postprocessing Poses of coordinate frames (Figure 3) attached to the elbow (HE), the forearm (HF), the dorsal aspect of hand (HD), and the object (HO) can be estimated from 3D positions of markers for each subject. Transformation matrices [7] describing the poses of forearm with respect to the elbow (TEF), the dorsal aspect of hand with respect to the forearm (TFD), and the object with respect to the dorsal aspect of hand (TDO) can be decomposed into product of position (P) and rotation (R) matrices (PEFREF, PFDRFD, PDORDO). If the axes of the coordinate frames are aligned with the axes of

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Fig. 2 Hand postures: the initial pose (a), holding a glass - hold (b),

Fig. 3 Coordinate frames describing postures of elbow,

fastening a light bulb - screw (c), throwing an object - throw (d)

forearm, hand, and object

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III. RESULTS

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rotation of joints and the origins of coordinate frames are positioned into the centers of joint rotation, than hand anthropometry and motion of joints can be described by the corresponding position and rotation matrices. Each rotation matrix can be represented by a sequence of three rotations around axes z, x, and y for rotation angles (roll - R), (pitch - P), and (yaw - Y). Three sets of RPY angles are calculated from the rotation matrices (REF, RFD, and RDO) comprised in transformation matrices (TEF, TFD, and TDO). Transformation matrices are assessed at the time instant when the task is completed, i.e. when the real object displayed in VE is aligned with the target object.

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Twelve volunteers with no deficiencies in functionality of their right hand participated in this study. All subjects were able to reach the target poses of object. The results are shown as mean values of RPY angles with accompanying standard deviations (Figure 4). In figure panel (a) we present relative rotations of forearm with respect to elbow. Relative rotations of the dorsal aspect of hand with respect to forearm are depicted in figure panel (b), while collective activity of fingers with respect to the dorsal aspect of hand, are presented in panel (c). RPY angles calculated from the rotation matrices can be associated with movements of elbow, wrist, and finger joints in the following way. P angles calculated from matrices TEF describe forearm rotation (Figure 3, HF, P). Flexion/extension of the wrist is related to R angles obtained from matrices TFD (Figure 3, HD, R), while Y angles calculated from matrices TFD describe radial/ulnar deviation of the wrist (Figure 3, HD, Y). Matrices TDO contain information on the collective movements of fingers. R angles are related to the rotation of object in the plane parallel to the dorsal aspect of hand (Figure 3, HO, R). Y angles describe rotation of object around the axis which goes through the centre of gravity (COG) of the object and is parallel to the side of the object where fingertip contacts occur (Figure 3, HO, Y). P angles obtained form matrices TDO describe rotation of object around the axis passing through the tip of thumb and the COG of the object. The task “hold” requires repositioning of the object from the initial into the upright pose. This is achieved primarily by rotating the forearm (P, Figure 4a). Radial/ulnar deviation (Y) and flexion/extension (R) of the wrist (Figure 4b) translate the object to the target position, while fine tuning of the object orientation is achieved by rotating the object in the plane parallel to the dorsal aspect of the hand (R, Figure 4c).

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Fig. 4 RPY angles assessed after rotation of arm and hand segments when the real object coincides with a target pose: forearm with respect to elbow (a), dorsal aspect of hand with respect to forearm (b), and object with respect to dorsal aspect of hand (c)

The elbow joint is close to its limit of range of motion when performing the “screw” movement. The forearm rotates in the opposite direction (P, Figure 4a) and is notably smaller than in the “hold” movement. Considerable amount of object rotation is performed by fingers (R, Figure 4c). The same observation is valid for the movement when shifting the object into the “throw” pose. The forearm is even less rotated (P, Figure 4a) while the rest of the movement is

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Assessment of hand kinematics and its control in dexterous manipulation

distributed between the wrist joint (Figure 4b) and fingers (Figure 4c). Standard deviations of RPY angles remain below 10° in almost all cases, except for the forearm rotation while performing screw movements and P angles extracted from the matrices RFD while performing the hold movements. In these two cases standard deviations reached 12°.

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can be obtained. It can be also established to what extent the fingers can change the orientation of the object. In this investigation, typical movements of forearm, hand, and fingers of unimpaired subjects at performing manipulation of an object were obtained. These data can serve as reference in further studies of patients with neuromuscular impairments.

ACKNOWLEDGMENT

IV. CONCLUSION The described VR system for assessment and training of hand dexterity is based on conventional PC and motion tracking device. VE is used to provide an augmented feedback, while the haptic information is completely preserved. The poses of target object are first recorded for one subject (a virtual trainer) and are adapted online for different sizes of hand. The system requires minimal intervention when adding new manipulation tasks. The results of the investigation show that precise model of the hand does not necessarily have to be built to design the tasks. However, several dimensions of the hand have to be acquired online during the start up of the system in order to perform the normalization. Standard deviations of rotation angles obtained for the whole group of subjects are relatively high when compared to the range of motion of wrist and elbow joints. Large standard deviations can be explained by the kinematic redundancy of the hand. When performing e.g. screw movement a subject can choose between rotating the forearm and moving the fingers. The angle of rotation performed by forearm, fingers, and wrist also depends on the current posture of the hand and especially on the vicinity of joints to the limits of range of motion. The method can be implemented by any other costefficient motion tracking system such as a PC compatible magnetic tracking system. The approach proposed enables offline analysis of subject’s performance. Angles in individual joints cannot be assessed accurately, nevertheless an indication of control abilities over elbow and wrist joints

This project was supported by the Slovenian Research Agency. The authors are grateful to Gregorij Kurillo for many productive ideas and comments during work.

REFERENCES 1. 2. 3. 4. 5. 6. 7.

Roby-Brami A, Jacobs S, Bennis N, Levin MF (2003) Hand orientation for grasping and arm joint rotation patterns in healthy subjects and hemiparetic stroke patients. Brain Res 969(1-2):217-229 Scholz JP, Schoner G, Latash ML (2000) Identifying the control structure of multijoint coordination during pistol shooting. Exp Brain Res 135(3):382-404 Wang X (1999) Three-dimensional kinematic analysis of influence of hand orientation and joint limits on the arm postures and movements. Biol Cybern 80(6):449-463. Jeannerod M (1981) Intersegmental coordination during reaching at natural visual objects. Lawrence Erlbaum, New York Mamassian P (1997) Prehension of objects oriented in threedimensional space. Exp Brain Res 114(22):235-245 Supuk T, Kodek T, Bajd T (2005) Estimation of hand preshaping during human grasping. Med Eng Phys 27(9):790-797 Sciavicco L, Siciliano B (2002) Modelling and control of robot manipulators. Springer-Verlag, London Address of the corresponding author: Author: Institute: Street: City: Country: Email:

Mitja Veber Faculty of Electrical Engineering Trzaska cesta 25 Ljubljana Slovenija [email protected]

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Can haptic interface be used for evaluating upper limb prosthesis in children and adults H. Burger1, D. Brezovar1, S. Kotnik1, A Bardorfer2 and M. Munih2 1

2

Institute for Rehabilitation, Linhartova 51, Ljubljana, Slovenia Faculty for Electrical Engineering, Tržaška 25, Ljubljana, Slovenia

Abstract— There is a lack of objective measurement methods for assessing upper limb prosthetic use in adults and children. The aim of the present study was to find out whether haptic interface could be used for that purpose. Fifty-five adults and twenty-three children were included into the study. All were tested by UNB observational test and haptic interface, and they filled in one or two questionnaires. Haptic interface showed differences between hands and prostheses, the results depended on the age of a child or adult and correlated with the amputation level and the stump length. Correlations were also found among the results of haptic interface, UNB test and questionnaires. It was not demonstrated that the results of haptic interface depended on the time from amputation to fitting with the first prosthesis, or amputation of the dominant hand. It was not possible to test subjects after shoulder disarticulation or very high trans-humeral amputation. Haptic interface seems a promising tool for assessing upper limb prosthetic use in adults and children after trans-radial amputation. Keywords— upper limb amputation, prosthesis, rehabilitation, outcome measurement, haptic interface

I. INTRODUCTION Human hand is a very complex organ with many different functions and its functional integrity is essential for many activities. Upper limb amputation is a great catastrophe for an individual. A primary rehabilitation goal after upper limb amputation is the achievement of maximal functional ability and independence at home, at work or at school and in the community [1]. Engineers have developed new sophisticated and also very expensive prosthetic components; however, their benefits for users have not really been explicitly demonstrated. Unfortunately there are not many measurement methods and outcome measures for assessing rehabilitation outcome after upper limb amputation or benefits of different prosthetic components, especially not for adults. In general there are two methods that can be used for the assessment of hand and upper limb prosthetic function. These are observational tests and questionnaires. By means of an observational test a person is assessed in clinical environment, which is not necessarily the same as home envi-

ronment. Furthermore, the test is therapist-subjective and more time consuming than questionnaires. Questionnaires are subjective both for adults or children, but less time is needed to fill them in and subjects answer how they perform an activity in their real environment in every day life. For very young children, answers are based on parental answers which are not always completely realistic. There is no absolutely objective measurement method that would measure hand function at the activity level and not only at the level of body function. The aim of present study was to find out whether haptic interface could be used for the evaluation of upper limb prosthetic use in children and adults. II. SUBJECTS AND METHODS Fifty-five adults with upper limb amputation who had finished rehabilitation at the Institute for Rehabilitation in Ljubljana at least one year prior to the study, and twentythree children, the sum total of the patients at the children’s upper limb prosthetic clinic at the Rehabilitation Institute in Ljubljana, Slovenia, were included into the study. All of them had been fitted with a prosthesis at least one year before the testing. The skill at performing five different tasks in virtual environment was tested by a haptic interface (robot) as a measuring device. The tasks can be divided into three groups: tasks for measuring accuracy (points hitting, linear and circular tracking), task for measuring velocity and accuracy (labyrinth) and a maximal force task. At “points hitting” the subjects had to hit a point which was randomly changing its position. At “linear and circular tracking” the subject had to follow a ball on a straight or circular line in two directions – firstly, outwards or counter clockwise and secondly, inwards or clockwise. At “labyrinth” the subjects had to go through a labyrinth as fast as possible without hitting its wall. At “maximal force tasks” the subjects had to follow a straight line against the opposing force of 50N. All the tasks were measured by a custom-built virtual reality simulator consisting of a PHANTOM Premium 1.5 haptic interface and a graphics workstation [2]. The simula-

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tor provided visual and tactile (force) feedback to the subjects. The healthy (non- amputated) upper extremity was always tested first, followed by the amputated side. All the subjects used their prostheses. All the adults filled in two questionnaires in a form of an interview; firstly, the ABILHAND [3] and secondly, the part of the OPUS [4] questionnaire on upper extremity function. All the children and adults were tested by the University of New Brunswick (UNB) test of prosthetic function [5] which was specially developed for assessing children. The UNB test assesses ten developmentally based, ageappropriate activities in 2 to 13-year-old children. It is also appropriate for testing adolescents above the age of 13, using the activities for 11 – 13 year-olds [6]. It assesses the spontaneity and skill of prosthetic use. The subtests for 11 – 13 years were used for the adults. For children younger than seven years, their parents filled in a Child Amputee Prosthetics Project – Functional Status Inventory for Preschool children (CAPP-FSIP) [7], while older children filled in Child Amputee Prosthetics Project – Functional Status Inventory (CAPP-FSI) [8] by themselves. III. RESULTS A. Adults Among the adults there were 42 (76.4%) men and 13 (23.6%) women, 56 years old on average (SD 17 years). Two thirds had trans-radial amputation. At testing, 75% had esthetic prosthesis, 13.5% body powered, 3.8% myoelectric and 7.7% passive prosthesis with terminal device for work. The measurement with haptic interface was not possible on the amputated side in both subjects after shoulder disarticulation and in six out of nine subjects after trans humeral amputation due to too limited ROM in the shoulder joint. In 12 subjects after trans-radial amputation who had esthetic prosthesis, it was not possible to fix the haptic interface stick properly and their measurements were excluded from further analysis. Valid measurements on both sides were done on 28 adult subjects. At all five measured task, the results of the tests were lower when performed with the prosthesis. Differences were observed in almost all of the measured parameters. Many measured parameters correlated with the clinical parameters, the results of UNB test and questionnaires. The elderly subjects had greater maximal and average deviation from the tracking trajectory at linear (Figure 1) and circular tracking (maximal deviation linear r = .33, p < .01, average deviation r = .28, p < .05, circular tracking maximal devia-

Fig. 1 Results of linear tracking without disturbances in 74 years (upper part) and 45 years (lower part), both with prosthesis

tion r = .35, p < .05, average deviation r 0 .27, p < .05) with the prosthesis. The results achieved by the hand correlated only with the maximal deviation on both tests. The subjects with higher UNB activity score achieved higher end point velocity using their hand on both linear (r = .55, p < .05) and circular tracking (r = .63, p < .01), did both tasks quicker (linear r = .52, p < .05, circular r = .70, p < .01) and had greater absolute power of the patient movement contribution at both tasks (linear r = .62, p = .01, circular r = .61, p < .01). The results of the CIR questionnaire had no influence on linear and circular tracking with the prosthesis. Likewise, the results of ABILHAND questionnaire correlated with the results of the hand only. The elderly subjects needed more time to come through the labyrinth (r= .36, p +b ≥ 1 where denotes scalar product.

(3)

In [5] the authors show that SVM can be used to obtain CNN templates, by vectorizing the templates and adjusting the margin of learning problem. The main advantage of the approach [5] is that the templates can be learned from positive and negative samples. In the learning process every pixel of the image is transformed into a learning sample which contains the pixel’s neighborhood and CNN internal state. This can result in a large number of features and huge number of learning samples. For example, in the case of template size 15 the number of learning features is 450, while in the case of image size 352x288 pixels, the 101376 of learning samples can be generated per image. IV. CNN STABILITY

The notion of stability of CNNs is very important from application point of view, especially in the domain of image segmentation, since it is imperative to produce deterministic and constant performance independent of an input image with completely stable solutions [6]. With application of SVMs to CNNs, the templates can be produced that do not necessarily meet stability requirements, therefore the modification of learning problem is necessary to generate only completely stable solutions. It has been proven that CNNs with reciprocal templates are completely stable [7]. This defines a class of acceptable templates for the segmentation problem, where different restraints that conform to the findings in [7] can be established. By applying constraints on the learning problem to symmetric templates, the main advantage is a lower number of template independent coefficients that have to be computed. This means a search space reduction obtained by the lower number of features for learning instances and, consequently, by the smaller size of learning problem. It is also important to notice that with the introduction of constrains expressive power of CNN is reduced and the acceptable set of templates cannot outperform the CNN with no constraints. To constrain the learning problem, the constraints have to be introduced in the learning phase of SVM. This requires a modification of the scalar product calculation, and the corresponding alpha coefficients and weight vector of SVM. Since SVMs with linear kernels are utilized, and the CNNs are based on the same scalar product as linear SVMs (Eq. (1), Eq. (3)), the same effect can be achieved by transforming the input vectors and extracted output weight appropriately. New learning features are constructed by summing up the corresponding values that are multiplied by the same coefficient. The number of learning features is reduced to twice the number of independent coefficients (one set for every CNN

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Obtaining completely stable cellular neural network templates for ultrasound image segmentation

template), so different constraints can be used for individual templates. Coefficients, extracted from the weight vector w, are then simply placed on the appropriate position in the CNN templates. In this paper, we utilize the constraint of symmetry, based on Euclidean distance from the template center. The same coefficient multiplies the pixels that have the same distance from center, producing circular symmetric and completely stable solutions. V. SEGMENTATION OF OVARIAN ULTRASOUND IMAGES USING SYMMETRIC CNN TEMPLATES TRAINED BY SVM

A complete understanding of ovarian follicle dynamics is crucial for the field of in-vitro fertilization. The main task is to succeed in determining the dominant follicles which have a potential to ovulate. For credible results, a doctor must examine patients every day during their entire menstrual cycle. Examination is usually done with ultrasonography. Because of the tedious and time-consuming nature of manual follicle segmentation, which is, on the other hand, also very demanding and inaccurate, an automated, computerbased method is desirable. Segmentation of ultrasound images using the CNNs has been discussed in [8, 9] and the application of SVMs to this problem in [5].

Fig. 1. (a) Original ultrasound image, (b) segmented by leading expert In order to test our optimization method we tried to obtain the CNN templates for a rough detection of ovarian follicles. Our learning set consisted of 4 images, while the testing set consisted of 28 images, randomly selected from a database of 1500 ultrasound ovarian images. The selected images belong to 12 different patients. A leading expert manually annotated the positions of follicles and ovary in every image (an example of segmentation is depicted in Figure 1). The real unfiltered ultrasound images, with left and right top black regions removed, were used as an input to our method, both in learning and testing phase. Ultrasound images were sampled from the VHS tape using the MiroVideo DC30+ video card. A full resolution sampling to

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720x540 pixels and highest possible quality of JPEG movie (compression 2.66:1) were performed. However, it should be stressed that the VHS system is interlaced, where every image resolution is only 352x288 pixels for PAL. After sampling all images were converted in 256 gray levels. From each image in our experiment it is possible to generate 101376 learning samples. Bigger learning sets can reduce errors in testing sets, but can also be quite time consuming, especially in the case of non-consistent samples. These always appear in the annotated images, because even the leading experts cannot precisely identify all the follicles. Therefore we decided to subsample the images according the CNN template size. Thus, the size of a single learning sample (number of features) varies with the template size. For this experiment we selected templates of size 7, which then generated 2185 learning samples. In the case of fully independent coefficients 98 features (pixels) for every template were generated. Applying a symmetric Euclidean distance template reduced the number of features from 98 to 20. Learning process took less then a minute for every template on an average today's PC hardware. Nevertheless, the speedup for constrained template calculations compared to unrestrained was 1.77. We verified the follicle recognition quality by using the so called ratios ρ1 and ρ2 [10]. This metrics measures sensitivity and specificity of an image recognition algorithm. It calculates the intersections of the recognized and referential (annotated) image regions. ρ1 stands for the ratio between the areas of intersection and annotated follicle, while ρ2 for the ratio between the areas of intersection and recognized region. If the recognized regions entirely cover the annotated regions, then both ratios ρ1 and ρ2 are 1. In general, the closer the values of ρ1 and ρ2 to 1, the better is the matching of the regions being compared. We validated our proposed learning and detection algorithm by observing only ρ 2. If the recognized, i.e. segmented, region of a follicle gives ρ2, we consider it a proper detection of the corresponding annotated follicle. This criterion warranties that more than a half of any recognized follicle region overlays a particular annotated follicle. To asses our new method with completely stable templates, a comparison between fully independent and constrained calculation of template coefficients was made. For each iteration, a new set of templates is obtained for the constrained and unconstrained approach. The resulting CNN with multiple time-variant templates can be seen as stacking ensemble classification approach in the field of machine learning, but with major difference of exploiting the internal state information about the confidence level, and not only the final classification.

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contrast to the conventional ones whose parameters are stationary. Despite the reduction of the expressive power of CNN by introducing the constraints that produce completely stable solutions, first iterations of segmentation results are comparable to the ones obtained with no restriction. Better results of unconstrained approach are probably the result of application CNN with time variant templates. We expect better results with the approach that utilizes time invariant templates.

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REFERENCES We compared identified follicles to annotated ones by observing true positive and false positive follicle identifications with respect to previously defined criteria. This comparison was made for different number of iteration and the corresponding number of time-variant templates. The true positive rate is presented in Fig. 2 It can be seen that the true positive rate of constrained templates is comparable to the unconstrained templates and shows a slightly better performance for certain iterations. On other hand, the detection rate of follicles increases and in many cases other structures on ultrasound images are recognized. Therefore by increasing the number of iterations also the false positive rate increases in both constrained and unconstrained templates as shown in Fig. 3. It has to be noted that all the templates were obtained with the same learning parameters despite the different problem sizes. By adjusting this SVM parameters, better results might be obtained compared to the unconstrained approach. 60% 58% 55% 53% 50% 48% 45% 43% 40% 38% 35% Sy m m e t r ic

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VI. CONCLUSIONS

A novel approach based on SVM for the CNN template optimization with completely stable templates was presented in this paper. Because of different way of learning, the CNN templates obtained this way are time-variant, in

1.

Chua L. O. and Yang L. (1988), Cellular Neural Networks: Theory, IEEE Transactions on Circuits and systems, Vol. 35, Num. 35, pp 1257-1272 2. J. J. Hopfield (1982), Neural Networks and Physical Systems with Emergent Computational Abilities, Porc. Natl. Acad. Sci., Vol. 79, Num. 8, pp 2554-2558 3. M. Hänggi and G. S. Moschzty (2000), Cellular Neural Network: Analysis, Design and Optimisation, Kluwer Academic Publishers, Boston, USA 4. V. N. Vapnik (1995), The nature of statistical learning theory, Springer, New York 5. B. Cigale, M. Lenic, D. Zazula (2006), Segmentation of ovarian ultrasound images using cellular neural networks trained by support vector machines, Knowledge-based intelligent information and engineering systems, pp 515-521 6. Gabriele Manganaro, P. Arena, L. Fortuna (1999), Cellular Neural Networks: Chaos, Complexity and VLSI Processing, Springer, Berlin, Germany 7. L. O. Chua, L. Yang (1988), Cellular Neural Networks: Theory, IEEE Transactions on Circuits and Systems 35, pp 12571272. 8. D. Zazula and B. Cigale (2006), Intelligent Segmentation of Ultrasound Images Using Cellular Neural Networks, Intelligent Processing Paradigms in Recognition and Classification of Astrophysical and Medical Images, In press 9. B. Cigale and D. Zazula (2004), Segmentation of Ovarian Ultrasound Images Using Cellular Neural Networks, IJPRAI, Vol. 18, Num. 4, pp 563-581 10. B. Potocnik and D. Zazula (2002), Automated Analysis of a Sequence of Ovarian Ultrasound Images. Part I, Imag. Vis. Comput., Vol. 20, Num. 3, pp 217-22 Author: Institute: Street: City: Country: Email:

Mitja Lenic University of Maribor Smetanova 17 Maribor Slovenia [email protected]

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Segmentation of 3D Ovarian Ultrasound Volumes using Continuous Wavelet Transform B. Cigale and D. Zazula University of Maribor, Slovenia Abstract— A novel algorithm for the segmentation of 3D ultrasound images of ovary is presented in this paper. The algorithm is based on continuous wavelet transform (CWT) and consists of two consecutive steps. In the first step, the centers of follicles are determined by tracing the local maxima from higher to lower scale in the wavelet transform of input images. The center of follicle appears as local maximum near value 0 when the size of the follicle corresponds to the scale of CWT. In the second step, the shape of the follicle is outlined. This is done by casting the rays in different directions from the center of the follicle in order to find its border. The position of border is connected with the wavelet scale and the position of the first local minimum on each ray. The method was tested on a small set of real 3D ultrasound images. The results were evaluated visually, since we do not have manually annotated images. Keywords— 3D ultrasound images, ovarian follicles, continuous wavelet transform, segmentation.

I. INTRODUCTION A complete understanding of ovarian follicle dynamics is crucial for the field of in-vitro fertilization. The main task is to succeed in determining dominant follicles which have a potential to ovulate. There are theories that suggest that the dominant follicle can be determined by studying the dynamics of follicle growth. To support or to reject this theory many examinations should be done on the same patient through the period of several days using an ultrasound machine. Such procedure is laborious and error prone, thus an automated procedure is desired. One of the steps to achieve this goal is automated segmentation of follicles in the images. In our case we used 3D ultrasound images. There are many algorithms which enable automated or semi-automated segmentation of 2D ovarian ultrasound images [1, 2, 3], but only a few of them can be extended to 3D images that provide more information. In this paper we present a novel approach based on continuous wavelet transform (CWT). In Section II, where we make a small introduction to the CWT, we also make some observations about its behavior at abrupt changes in 1D lines. The observations are then extended to an algorithm which firstly detects the follicle in the image and then determines its shape. In section III, we interpret the results of our algorithm on real images. The

obtained results are discussed in section IV, which also concludes the paper. II. SEGMENTATION OF FOLLICLES A. Homogeneous areas and CWT In this subsection, we are making a short introduction to the CWT and also presenting some interesting characteristics, which will be used later in the derivation of our algorithm. Wavelet transform is actually a convolution between the signal f(x) and the function ψ(x) called wavelet, defined as

W ( a, b ) =

1 a

∞

∫ f (x ) ⋅ψ

−∞

x−b⎞ ⎜ ⎟ ⋅ dx. , ⎝ a ⎠

*⎛

(1)

where a stands for scale and b for a time shift. The wavelet function ψ(x) must be localized both in time and frequency, and should be admissible, which, for an integrable function, means that its average should be zero [4]. A wavelet can be dilated using the scale parameter a and translated by parameter b. Since wavelets are zeromean, a wavelet transform measures the variation of function in a neighborhood of b whose size is proportional to a. Thus, sharp signal transitions create large amplitude wavelet coefficients. Mexican hat (MH) is a wavelet widely used in image processing for edge detection [5]. The function is symmetrical and the axis of symmetry of the 1D MH wavelet is at x=0. Strictly speaking, the MH wavelet is not localized in time but it can be easily observed that it will only deviate significantly from zero in the vicinity of x=0. This interval is called the effective support and is usually limited to the interval [-5,5] as in [6]. We define localized Mexican hat wavelet as

(

)

2 ⎧ 2 −x ⋅ x 2 − 1 ⋅ e 2 , if x ≤ 5, ⎪ ψ (x ) = ⎨ 4 π 3 ⎪ 0, otherwise. ⎩

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1017–1020, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

(2)

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B. Cigale and D. Zazula WHa=2,m=5L

changes to a local minimum. This clarifies that the wavelet at scale a is not appropriate for the search of the centers of objects narrower than 2a. Let us assume that m>5a. It becomes clear that W(a,0)>0, since the MH wavelet defined as in (2) has slightly positive average. If the support of the wavelet were not limited, then W(a,0) would be a little bit less than 0.

0.6 0.4 0.2 -10

-5

5

10

b

-0.2 -0.4

B. Detection of the centers of follicles

-0.6

Fig. 1 The result of wavelet transform when m90%) agreed or strongly agreed with the statements, the purpose of clinical alarms, and the need for prioritized and easily-differentiated audible and visual alarms.

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Improving Patient Safety Through Clinical Alarms Management

Likewise, a large portion of respondents identified nuisance alarms as problematic, with the large majority agreeing or strongly agreeing that they occur frequently (81%), disrupt patient care (77%), and can reduce trust in alarms and cause caregivers to disable them (78%). 80% support smart alarms which can help minimize some types of nuisance alarms 49% of respondents believe that a dedicated central alarm management staff (i.e., monitor watchers) for disseminating alarm information to caregivers is helpful, while 34% were neutral; 54% of respondents see utility in integrating alarm information with communications systems (e.g., pagers, cell phones), while 30% were neutral. Responses were split on whether properly setting alarm parameters is overly complex on existing systems. 49% of respondents disagreed or strongly disagreed with this statement, while 28% agreed or strongly agreed and 23% responded as neutral on the issue. 72% of respondents agreed or strongly agreed that alarms are adequate to alert staff to changes in the patient’s condition. Third Section provided insight into rating the relative contributions of various challenges faced with clinical alarm management. For most of the items, responses were welldistributed across the range of importance. However, two items showed more consistency. 42% of respondents consider “frequent false alarms reducing attention” and “response to alarms” as the most important of the presented issues, and 78% rated false alarms in the top four rankings. Conversely, 25% of respondents believe lack of training on alarms is the least important issue, and 63% rated it at the lowest ranking - 6 through 9. Many nurses see alarms as one item on a long list of tasks to be managed, rather than as an enabling tool that improves the nursing staff’s ability to stay informed of their patients’ conditions. By not recognizing the importance of training, the results indicate that nurses may underestimate their role in alarm management and see the “burden” of clinical alarms as solely a technology problem. Clearly, frequent nuisance alarms have played a role in breeding this mindset, and technology improvements are a necessary component in addressing this problem. Thus, effective clinical alarm management relies on (1) equipment designs that promote appropriate use (e.g., easy to set, obvious visual indictors when alarms have been disabled), (2) clinicians taking an active role in learning how to use equipment safely over its full range of capabilities, and (3) hospitals recognizing the complexities of clinical alarm management and devoting the necessary resources to develop effective management schemes. As stated by one survey respondent, a “combination of technology and nursing process adjustments need to be implemented in order to effectively address this issue. Smart alarms, improved communication systems, directing alarms to the caregivers,

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training, accountability regarding alarm response policies, etc, all should be helpful in reducing the risk.” IV. OBSERVATIONS The studies presented revealed several themes: • • • •

• • • • •

•

The number and complexity of alarm systems in critical care environments challenge human limits for recognition and action Alarms in critical care environments may not significantly affect care management decisions In general, alarms are a tool in assessing patient conditions should be used in conjunction with direct clinical measurements and observations The term “alarm” was found in the FDA MAUDE adverse event report Product Problem field most commonly for physiological monitoring systems, ventilators and infusion pumps Parameter acquisition improvements (e.g. pulse oximetry) are important in improving alarm accuracy and value Remote alarm communication devices (e.g. pagers) if well designed can be of value but problems have occurred when used as the primary alert method The IEC/ISO standards are viewed by many as a way to improve alarms by standardizing audible and visual alarms, priority and parameter differentiation The alarm problem is a systems issue and actions toward specific areas must consider their impact on the system There is disagreement about the role of user operation of alarm systems in alarm system performance. Caregivers de-emphasize the need for alarm configuration and operation training while adverse event analysts find many instances of improper setup and subsequent action when alarms do occur. False alarms have been consistently reported as a major issue with alarm systems. They reduce staff confidence in alarms which may result in deactivation of alarm systems and detract from care management V. RECOMMENDATIONS

A. Medical Device Industry Manufacturers should consider the complexity of the healthcare environment in order to design alarm systems that are operationally intuitive, and effective given the care tasks of users, and which are focused on the true need for

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Y. David, J. Tobey Clark, J. Ott, T. Bauld, B. Patail, I. Gieras, M. Shepherd, S. Miodownik, J. Heyman, O. Keil, A. Lipschultz, …

intervention. False alarms must be reduced for alarm systems to be effective. There must be additional emphasis on accurate parameter acquisition, human factors design and a systems approach to alarm systems. The IEC/ISO standards for alarm systems represent an improvement in design and should be considered for implementation in the U.S. Standardization offers the opportunity to eliminate some elements of confusion over what different alarms mean, as well as how they are operated. The actual use of recognized standards by various manufacturers must become the norm rather than the exception. Additional standards and standardization are also necessary so that devices that are commonly used together operate as a system rather than as a collection of individual components. Furthermore, how devices are configured must also reach a greater level of commonality. B. Healthcare Healthcare organizations and clinicians should recognize the limitations of alarm systems and utilize them only as a tool in the overall assessment of patient condition. It should be recognized that improper configuration and operation can result in adverse events in the complex patient care environment. Effective education and training must take place to better understand proper operation, the implications of mis-configuration or defeating alarms, and the limitations of current alarm systems. False alarms should not result in reduced alarm vigilance and deactivation of alarms. The care of patients where clinical alarms are used should be planned with input from clinical staff, biomedical/clinical engineers, facilities staff and others involved in the environment of care so that alarm use is well integrated with other procedures and requirements. Healthcare institutions should carefully evaluate the potential for devices to reduce false alarms and other cited problems through intelligent processing of incoming signals, the use of “smart alarm” technology, ease of use, usability and human factors design principles, and application of standardization and systems engineering measures. Consider implications of, interfacing and environmental factors in adding remote enunciator systems. C. Education Effective education for clinicians is a critical part of the process that needs to be considered when working to improve alarm-related safety. Clinicians need to be provided with plenty of opportunities to learn about the details of the alarm-based medical devices they are expected to operate. Such learning must reach the level of operational effective-

ness rather than just intellectual knowledge. Planning for this education needs to start during the technology planning and procurement process. Specifically, the cost for training clinicians on how to use devices with alarms needs to be included in the budgeting and implementation timeline for new technology procurement. Need to train clinicians once devices arrive and annual basis refresher courses, training of per diem or other staff. Training should include information on the institution’s alarm setting and response protocols. VI. FUTURE DIRECTIONS The results of this study lay the groundwork for future efforts towards improving the area of clinical alarms. Including: • • •

•

•

•

Developing awareness of the need to improve clinical alarms Soliciting the constituents to meet at focused forums to develop action plans to improve identified problem areas Promote to the medical device industry the critical need to reduce false alarms by a. enhanced parameter acquisition accuracy and employment of proven “smart alarms” technology to reduce false alarms b. better human factors engineering in alarm systems such as the use of more intuitive graphical user interfaces c. improved alarm integration and intelligence Bringing forth the data to standards bodies to promote alarm standardization improvements including the use of scientific research data in developing alarm standards such as a uniform method of annunciation (tone, display, etc.) for life critical versus other types of alarms Developing a better awareness by clinical staff of the criticality of alarms and deleterious effects of operational problems so that there can be an enhanced emphasis of the importance of training and preparation in the area of alarms Re-evaluate the area of clinical alarms in 1-2 years by administering a similar survey and other measures to determine progress in clinical alarm improvement Author: Institute: Street: City: Country: Email:

Yadin David Texas Children's Hospital 6621 Fannin Street Texas USA [email protected]

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Medical Equipment Inventorying and Installation of a Web-based Management System – Pilot Application in the Periphery of Crete, Greece Z.B. Bliznakov1, P.G. Malataras2 and N.E. Pallikarakis1 1

Department of Medical Physics, University of Patras, Patras, Greece 2 Institute of Biomedical Technology, Patras, Greece

Abstract— The development of an equipment inventory of the medical devices installed and used in the Peripheral Healthcare System (PHS) of Crete, Greece is considered to be the cornerstone for the initiation of a process for the evaluation, monitoring and management of biomedical technology in this institution. The medical equipment inventorying process is performed by the Institute of Biomedical Technology, in cooperation with the Biomedical Technology Unit from the Department of Medical Physics of the University of Patras, Greece. The whole procedure is divided and accomplished in three phases: 1) collection of medical equipment data on structured paper sheet forms; 2) data entry in a computerized management system; 3) installation of an in-house developed webbased medical equipment management system, called WEBPRAXIS, used to store and manage the medical equipment. As a result, the procedure leads to the creation of an electronic database, containing essential information for the identification of each medical device such as: equipment control number, device group, type and manufacturer, serial number, department and location, age and acquisition cost. Total number of 4 958 medical devices from 22 healthcare institutions are recorded. Furthermore, the medical equipment is classified in 355 device groups, 2 050 device types and 715 manufacturers. The current project overcomes a number of problems, present in the field of biomedical technology management in the PHS of Crete. The most important are: 1) ineffective practice of keeping local inventory files, due to insufficient information on codification and nomenclature standards; lack of computerized systems and software, and lack of personnel experience; 2) no centralized database for the medical equipment in PHS of Crete, resulting in poor technology management, assessment, planning and decision making. The systematic use of WEB-PRAXIS is expected to improve the management of medical equipment with significant benefits related to cost-efficiency and safety. Keywords— biomedical technology management, equipment inventory, web-based management system

I. INTRODUCTION The development of a medical equipment inventory is considered to be the cornerstone for the initiation of a process for evaluation, monitoring and management of biomedical technology. Whether equipment is used for diagnosis, monitoring of patient condition, or therapy, the

healthcare facility should ensure that the equipment is performing as intended by the manufacturer. This imposes the use of software tools, especially designed for medical equipment management as the only cost-effective solution. The current work presents the whole procedure of medical equipment inventorying and installation of a web-based management system in the Peripheral Healthcare System of Crete (PHS), Greece. II. MATERIALS & METHODS A. Background information Crete is the largest island in Greece. Situated in the Mediterranean Sea, it is the most south part of the country. It has an area of 8 300 square kilometers, a coastline of 1 040 kilometers, and a population of approximately 600 000 people. The Peripheral Healthcare System of Crete consists of 22 institutions, among which there are 8 hospitals and 14 medical centers. The procedure for inventorying of medical devices is performed by the Institute of Biomedical Technology (INBIT), in cooperation with the Biomedical Technology Unit (BIT unit) from the Department of Medical Physics at the University of Patras, Greece. The whole process is divided and accomplished in three phases: 1) collection of medical equipment data on structured paper sheet forms; 2) data entry in a computerized medical equipment management system; 3) installation of a web-based medical equipment management system. B. Collection of medical equipment data The first step of equipment inventorying procedure is to record the data of every single medical device on a structured paper sheet form. This is imposed by the needs for time saving and quick completion of the work, highest mobility of the working team, as well as, least possible interference in the hospital daily routines. For these purposes, a standardized data collection form is created. It comprises the following fields of information being recorded:

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1092–1095, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Medical Equipment Inventorying and Installation of a Web-based Management System

• • • • • • • • • • • • • • • • • • •

Device code - a unique identification code assigned to every single medical device. Hospital - code and name of the hospital, where the device belongs to. Parent system - applicable when the device is a part of a multi-modular system. Device group - code and nomenclature of the device group. Manufacturer - code and name of the device manufacturer. Model - the model of the device. Serial number - represents the serial number of the device. CE mark - indicator for CE marking of the device. Department - code and name of the department/clinic responsible for the device. Location - code and name of the location (room, ward, cabinet) where the device is in operation. Status - indicates the current status of a device at a given time. Supplier - code and name of the device supplier. Acquisition date - the date of the device acquisition. Manufacture year - the year when the device is manufactured. Installation date - the date when the device is installed in the hospital. Warranty expiration date - the date when the warranty for the device expires. Software - the software accompanying the device, if existing. Acquisition cost - the cost for purchase of the device. Comments - any other useful information is recorded.

The data collection procedure of medical equipment inventory is performed by a team, comprised of 8 specialized biomedical engineers and medical physicists, both from INBIT and BIT unit. The team is divided in 4 workgroups, each comprised of 2 people. Based on preliminary information, a time-plan is created and the responsibilities for each workgroup are assigned. Hospital-by-hospital, room-by-room, item-by-item, the 4 workgroups accomplish simultaneously collection of medical equipment data. Preliminary prepared labels, comprising information for the device code and hospital, are attached to each medical device, thus allowing easy and unique identification in the future. C. Data entry in a computerized medical equipment management system Once, the medical equipment data are collected on paper sheets, conversion to electronic format has to be accomplished. For this purpose, an in-house developed computerized medical equipment management system, called PRAXIS [1,2], is used to carry out data entry procedure and

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store the collected data in a relational database. It is a powerful software tool supporting the overall management of medical equipment in healthcare. Among the majority of PRAXIS features, some of them mostly related to specific procedure of medical equipment data entry are: • • • •

Special instruments used to facilitate and speed up the process of data entry. Preliminary inserted catalogs used for standardization of common names and nomenclatures. Network installation setup allowing several users to perform data entry simultaneously into the same database. Data consistency, security and backup.

Data entry procedure is carried out by the same team, performed the data collection in the hospitals. For this purpose, at the main office of INBIT in Patras, a customized network installation of PRAXIS with 5 workstations is accomplished. This allows 5 users to operate the system at the same time and to enter date into the same database. Time schedule is created and job activities are designated. At the end of each working day, a backup of the database is taken. All medical devices are classified following the coding and classification of device groups in compliance with the Universal Medical Device Nomenclature System (UMDNS) [3], developed by Emergency Care Research Institute (ECRI). D. Installation of a web-based medical equipment management system For the purposes of the project, a customized medical equipment management system, developed by INBIT, is used. The system, called WEB-PRAXIS, is designed and implemented on the basis of PRAXIS and it is its successor. It features several improvements and advantages, among which the most important related to the current work, are: • • •

Web-based application and service. Centralized database management. Facile support of application upgrade and data update from a distance.

At present, WEB-PRAXIS is developed using PHP open source code and is able to work with ORACLE or MySQL databases. The WEB-PRAXIS work environment allows the user to manage information contained in the database in a structured, effective and user-friendly way. There are six main areas as shown in the figure 1.

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Z.B. Bliznakov, P.G. Malataras and N.E. Pallikarakis System menu Main toolbar Linked information

Link buttons Data tables

Main area

Data summary

Fig. 1 Basic structure of WEB-PRAXIS workspace Data tables area lists all the records related to the specific form in a table format. The most important database fields are included and capability of information sorting, according to the desired field is provided. Main area presents all available information for the selected record and it is the area, where the record’s data is managed (inserted, deleted, updated, searched, etc.). Database fields are either compulsory (blue-colored) or non-compulsory (blackcolored). Link buttons open linking screens, where the user connects relative information from other screens to the specific record. Data summary is the area where the user obtains a comprehensive image of the whole data table, shown on the specific form. It contains information such as: total number of records; the specific number of the record currently reviewed; the time and the user of the last record modification; and the hospital to which the specific record belongs. Linked information is functionality that allows the user to link a specific record with relevant information, contained in a file (text, worksheet, picture, video, etc). A preview feature is available for majority of the file types, and allows the user to view the information, associated with the specific record at any time. Furthermore, the user can open the linked file to edit or update the information available. System menu and Main toolbar provide access to all the functionalities of the system and facilitate access to the

most common features used throughout the system operation. It provides easy navigation and managing information of the data tables, search, print, and export capabilities. III. RESULTS The whole procedure leads to the creation of an electronic database of medical equipment inventory of Crete Peripheral Healthcare System. Total number of 4 958 medical devices are recorded and classified. Table 1 shows the distribution of medical equipment among the 22 healthcare institutions. Furthermore, the total medical equipment inventory is classified by five different categories: device groups, device types, manufacturers, suppliers, and departments. The number of items for each category is shown in table 2. WEB-PRAXIS is installed on a central web server located at the administration office of the Peripheral Healthcare System of Crete. Each of the 22 healthcare institutions as clients connects to the central application and database by means of a web browser. No additional installations are required at the client sites. Access restrictions for each hospital users are assigned in order to retain security of data.

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Medical Equipment Inventorying and Installation of a Web-based Management System

Table 1 Medical device distribution by healthcare institution No 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22

Healthcare institution GH VENIZELEIO - PANANEIO IRAKLEIO UNIVERSITY HOSPITAL GH AGIOS NIKOLAOS GH-MC IERAPETRA GH-MC NEAPOLI GH-MC SITEIA GH RETHIMNO GH HANIA - AGIOS GEORGIOS MC KISSAMOS MC KANDANOS MC VAMOS MC PERAMA MC SPILI MC AGIA FOTEINI MC ANOGEIA MC MOIRES MC KASTELI MC AGIA VARVARA MC HARAKAS MC ARKALOHORI MC ANO VIANNOS MC TZERMIADO TOTAL

Medical devices 764 1675 457 212 48 170 276 855 34 42 27 39 37 27 45 39 45 34 33 33 39 27 4958

Table 2 Distribution of medical device categories Categories Device groups Device types Manufacturers Suppliers Departments

Items 355 2050 715 150 120

Prior to the present work, there is no centralized map for the medical equipment in PHS of Crete. This results in poor or limited technology management, assessment, incident reporting and lack of a reliable data-based planning decision making scheme for the distribution of medical instrumentation. V. CONCLUSIONS The core of a biomedical technology management program is the development of a comprehensive equipment inventory of the healthcare system. The creation of an equipment inventory serves the need for identification and control of all medical devices in the PHS of Crete. WEBPRAXIS addresses the needs associated with the services performed by the Clinical Engineering Departments related to all aspects of a medical device life cycle. The systematic use of WEB-PRAXIS is expected to improve the management of medical equipment with significant benefits related to cost-efficiency and safety.

ACKNOWLEDGMENT The authors would like to express their thanks to all the people from INBIT and BIT unit participating in current project for their valuable help. The work is financially supported by the Ministry of Health and Social Solidarities, Greece.

REFERENCES 1.

IV. DISCUSSION The current project reveals and tries to overcome a number of problems and deficiencies present in the field of biomedical technology management in the Peripheral Healthcare System of Crete. Some of the most important are the following: There is a rather non-uniform and ineffective practice of keeping local inventory files in the hospitals due to: insufficient information on codification and nomenclature practices and standards; lack of computerized systems and software, and lack of personnel experience.

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2. 3.

Bliznakov Z, Pappous G, Pallikarakis N (2002) Development of a Biomedical Technology Management System. 3rd European Symposium on Biomedical Engineering and Medical Physics, In Proceedings, Patras, Greece, 2002 Bliznakov Z, Pappous G, Bliznakova K, Pallikarakis N (2003) Integrated Software System for Improving Medical Equipment Management. Biomed. Instrum. Technol. 37(1):25-33 UMDNS at http://www.ecri.org/Products_and_Services/Products/ UMDNS/Default.aspx Author: Zhivko Bliznakov Institute: Street: City: Country: Email:

University of Patras Department of Medical Physics, School of Health Sciences Rio – Patras, 26500 Greece [email protected]

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MIDS-project – a National Approach to Increase Patient Safety through Improved Use of Medical Information Data Systems H. Terio Department Clinical Engineering, Karolinska University Hospital, Stockholm, Sweden Abstract— MIDS, Medical Information Data Systems is proposed as a term for systems consisting of medical devices and IT-systems. MIDS are used for collection of physiological data from patients and transferring this data through a computer network to serves and databases. The project showed that the manufacturers of IT-systems for health care and the users of them do not take their full responsibility for the development and implementation of the information safety and functionality. For example there is no clear routines how to secure the accuracy of the information that is transferred between different IT-systems. It is also a problem that the borderline between medical devices and IT-systems is unclear, which makes it difficult to decide what directives or legislation should be applied. This makes it also unclear who should support the systems and the project proposes guidelines to improve the situation. The project also showed that there is need for continuing education of the staff handling MIDS. Keywords— Medical devices, IT-systems, medical information systems, PEMS, MIDS.

I. INTRODUCTION The virus Sasser caused severe problems for several medical devices connected on a network, for example heart monitoring systems, PACS systems and CT, where images disappeared. A PACS system crashed and was down for three days after installation of new anti-virus program and security updates, patches from Microsoft. These are example from recent adverse events occurred in Sweden. An analysis of withdrawal of medical devices during 1992-1998 conducted by FDA, showed that out of 3140 cases 8% were depended on software problems and 80% were depended on changes made after production and distribution of the software. Very often these problems are connected to other software like anti virus software that are running parallel to the application software. The development of medical devices and IT-technology has made it possible to use new technological solutions within health care. Medical information systems are to day connected directly to medical devices in order to retrieve physiological data or to control the function of the medical devices. IT-systems and software used in health care have obtained more crucial importance for the treatment and care of an individual patient. These systems are often even life

supporting. Shortcomings and defects in the software can constitute a risk for injuries or they can even harm the patient. Integration of medical devices and IT and the use of the devices in networks have made it necessary to find a new notion describing the integration of the two areas. The proposed new acronym is MIDS that stands for Medical Information Data System, which are medical devices integrated with IT-products/systems that are used to collect physiological data for diagnosis and/or treatment of a patient and transfer this data through a network to a server/database. The use of MIDS increases the requirements for higher competence in the persons who handle these systems. It is also necessary to develop the co-operation between clinical engineers and IT-engineers. The Swedish Society for Medical Engineering and Medical Physics (MTF) started a project in December 2005 that aim to improve patient safety through clarification of responsibilities for work with MIDS. The project aims to give a proposal for national requirements for competence that engineers working with MIDS should have and also guidelines for co-operation between Clinical Engineering (CED) and IT departments in order to fulfill the demands that directives and legislation state. II. METHOD Information and data that has been used for development of the proposals was collected by interviews of different professionals, using questionnaires and survey of legislation and literature. Discussions and exchange of experience among the members of the project and reference groups have also been of importance. One of the first areas that was mapped during the project was how the MIDS are used and handled in the hospitals. The current level of competence and what continuing education the engineers, working in the field felt that they needed was clarified by a questionnaire posted on the MTF website. This special MIDS-portal was designed specially to inform MTF’s members and public. The project members had their own web based project place where all the documentation was collected and it was also used for project administration.

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H. Terio

The project group arranged seminars where the progress of the project was reported and where it was possible to exchange information with different professionals. Participation at different national meetings and debates has also been a good forum for information exchange. The project group had members from the largest university hospital in the country as well as from smaller regional hospitals and some of the organizations that work with medical informatics. The board of MTF was the steering group and the reference group was composed of representatives from national health care organisations and some representatives form county councils and person working with higher education. III. RESULTS A. MIDS components The average MIDS consist of the medical device itself that very often is based on computer with application software or it delivers data to a computer. It can be connected directly to a network, but often the connection is through an external computer. The data is usually analyzed on a client or a workstation, which is mostly an ordinary personal computer, even though there is a number of systems where the analysis are performed on the medical device itself. On these computers the application software, classified as a medical product, must work together with other software. The network where MIDS are connected can be a Local Area Network (LAN) functioning within a single clinic for collection and analysis of data for diagnosis of patients. However, in large hospitals and in cases where several people need to share the information, MIDS are one part of the general IT-infrastructure. In the latter case the manufacturer can demand that the hospital must use a segmented physical network or firewalls and Access Control Lists (ACL). The systems must be designed so that a stop in a network will not jeopardize the patient safety according to directives. Continuous monitoring of the network function is needed when using segmentation and intelligent switches for network traffic control. Quite often the servers and databases used in MIDS are not of the latest design. This means that one has to use operative systems that are not approved by the IT-department at the hospital. The manufacture can also demand that the database is installed on a separate physical server. In all cases it is required that verified and validated anti-virus software is used. Likewise, the patches used must be verified and validated for the application software. MIDS are used in most of the different parts of the modern health care. The different imaging systems are perhaps

the most well know, like CT, MRI, ultrasound etc. with accompanying storage and communication systems. Laboratories with their sophisticated analysis systems connected to Laboratory Information System (LIS) must follow even the In Vitro Diagnostic Directive (IVDD). Digital ECG, EEG and EMG equipment are examples of electro medical MIDS. Monitoring systems like the Patient Data Management System (PDMS) used for example in intensive care are very demanding since they are connected to a number of medial devices collecting vital data from patients in very serious conditions. These systems communicate also with Electronic Health Record (EHR) systems and LIS, which make the system sensitive for disturbances. Also the systems used with telemedicine and home health care are classified as MIDS. B. Regulation and requirements The Medical Products Agency is the Swedish national authority responsible for regulation and surveillance of the development, manufacturing and sale of drugs and other medicinal products like medical devices. They have together with the National Board of Health and Welfare, classified a software based patient data management system as a medical device. This means that the manufacturer has much greater obligation to make risk analyses and test the product according to the Medical Devices Directive (MDD). The quality of a medical device is mainly depended on how it is designed, developed and produced. But, the quality of software depends instead mainly on its design and development and almost not at all on its production that is carried out by copying the code, which easily can be verified. Most of the software problems can be traced back to shortcomings in design and mistakes made during the development. This new situation has also brought about need to revision of European directives and international standards. The revised version of MDD, 93/42/EEC states in the first article, paragraph 2 point (a) that “a ‘medical device’ means any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, together with any accessories, including the software necessary for its proper application intended by the manufacturer to be used for medical purposes for human beings…” In Annex I, section II “Requirements regarding design and construction”, the item 12.1b states: “For devices which incorporate software or which are medical software in themselves, the software must be validated according to the state of the art taking into account the principles of development lifecycle, risk management, validation and verification.” In the 3rd edition of IEC 60601-1:2005 there is a number of requirements that the Programmable Electrical Medical

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Systems (PEMS) must meet. Since medical devices will sometimes be used together to create a system, which is likely to become more frequent with the increasing use of computers to analyze clinical data and control treatment. Sometimes medical devices are designed by the manufacturer to work with other medical devices, however, it will often be the case that the separate medical devices are not designed to work with each other. Therefore, the standard also require that there should be someone in the organisation who is responsible for ensuring that all the separate medical devices work together satisfactorily in the integrated system; in other words, someone has to be responsible for designing the integrated system. It is recognized that the system integrator often has to comply with particular regulatory requirements. In order to perform its function, the system integrator needs to know: • • • • • • •

how the integrated system is intended to be used; the required performance of the integrated system; the intended configuration of the system; the constraints on the extendibility of the system; the specifications of all medical devices and other equipment to be integrated; the performance of each medical devices and other equipment; and the information flow in and around the system.

The IEC standard 62304 demands how the software for medical devices must be developed, documented, validated and supported. It also demands how the software must be classified depending on what type of injury that a possible malfunction can cause. C. Problems in connection with MIDS Specification of the function and technical requirements of large, complex MIDS are sometimes difficult to do, especially if there is not the competence needed at the hospital. Purchase of the system will then be done with imperfect documentation and this can lead to severe problems later on. It appeared during the project that sometimes the manufacturers and vendors have poor knowledge of the regulation and directives that govern the usage of the systems. For example the vendor in one case had a “Declaration of Conformity” for their system that was suppose to be connected to medical devices and to EHR. After the system installation it turned out that the development of the system was not finished and it was not possible to connect the system to the EHR. Handling of anti-virus software and patching of the operative system can lead to re-definition of the system. If the manufacturer has not validated the installed software or the patches, they can decline they liability with motivation that

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the system has not been used in an intended way. The system will then be classified as an in-house product and the user is liable for the whole system. Introduction of new MIDS or changes done on them should be combined with risk analysis. However, very often this is overlooked because there is no competence to carry out them. D. Competence requirements To survey the current competence of the engineers working with MIDS at the hospitals and the need of continuing education for these persons a questionnaire study was carried out. The questionnaire was sent out to personnel working in this area in every county in Sweden. Moreover, a number of persons with a good general view of the area were interviewed. The results showed that both the clinical engineers and IT-engineers were interested to enhance their knowledge on respective area. However, clinical engineers were more positive to take a supplementary examination in computer sciences and data communication than the ITengineers in subject on biomedical engineering. The results also showed that only half of the repliers considered that they had sufficient knowledge to use the MIDS they are working with. It can be concluded that there is a lack of knowledge within the MIDS-area and that there is need to define what competence is really required. This will also help the hospitals and county councils to plan for continuing education. E. Proposal for classification As a result of the project, a proposal for classification of computers used in MIDS was presented. This classification would make it easier to point out who is responsible for the support. All the computers, no matter if it is a thin client, server or workstation, have been divided in three main classes • • •

W is an ordinary computer with standard configuration, WM is an ordinary computer with standard configuration, but with a medical application, and M is a medical device with configuration in accordance of the regulations.

The computers are then grouped in three groups depending on where they are placed. • • •

Group 0 is outside the patient environment Group 1 is inside the patient environment with safety requirement according to IEC-60601 Group 2 is inside the patient environment with safety requirement according to IEC-60601 and IEC-529 Table 1 summarizes the classification of the computers.

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Table 1 Class W Class WM Class M

Classification of computers

Group 0

Group 1

Group 2

W0 WM0 M0

W1 WM1 M1

W2 WM2 M2

IT-department is responsible for the groups W-WM-WP computers and CED is responsible for the group M-MP computers. CED and IT co-operate on support of the groups WM and WP. In some cases there is difficulties to decide in which class the computer belongs and in such case CED and IT must discuss to clarify support responsibility. F. Proposal for technical solutions Special MIDS-domains were proposed to be created for the clients and servers at larger hospitals. In smaller hospitals Organizational Units in Microsoft Active Directory environment can be used. CED is proposed to be responsible for the MIDS-domain or the AD-environment for MIDS, whereas the IT-organization would be responsible for the general IT-infrastructure in the hospital. To increase the safety when usin MIDS segmented network with Access Control List should be introduced. Also labeling of the cables and workstations/clients should be used in order to separate MIDS and ordinary IT-systems. The cables used for MIDS are proposed to be green and for the IT-systems white. The labeling of the computers should follow the same convention. Anti-virus software with updating should be used for MIDS connected to a network. The function of MIDS should be verified and validated together with the user and the manufacturer. It is also recommended that there should be a general anti-virus administration with representation from CED and IT-department. They should supervise that the systems are managed according to regulations.

cal Informatics, CED, IT and biotechnology will be integrated in the new organisations to support the development of health care. To ensure the positive development for increased patient safety when using different MIDS, requires that CED and IT organizations develop their Quality Systems and work for certification of their work. The certification can be accomplished according to ISO 9000, ISO 13485, ISO 17025 and ISO 20000 or a combination of these standards. The two organisations can do the certification separately in the beginning but in the future they should do it together. Common product and system administration for CED and IT is recommended. On this way the routines, processes, cooperation and responsibilities will be ruled in a natural way. New functions like the System Integrator, described in the IEC 60601, 3rd edition, should be introduced as soon as possible in order to handle the MIDS in a proper way. This function should not be only a physical person, but a group of professionals from CED, IT and users system administration.

ACKNOWLEDGMENT This paper is based on the project report from the national MIDS-project. The leader of this project has been Salvatore Capizzello from the County Council of Norrbotten.

REFERENCES 1. 2. 3.

Medical Devices Directive (MDD) Directive 93/42/EEC–OJ 169/ 12.7.93 IEC 60601-1:2005, Medical electrical equipment – Part 1: General requirements for basic safety and essential performance IEC 62304, Ed. 1: Medical device software – Software life cycle process Author: Heikki Terio

IV. CONCLUSIONS Technical development and political decisions that direct the health care will require in the future that new interdisciplinary organisations be created within CED and IT. Medi-

Institute: Street: City: Country: Email:

Department of Clinical Engineering, C2:44 Karolinska University Hospital, Huddinge 141 86 Stockholm Sweden [email protected]

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Patient safety - a challenge for clinical engineering J.H. Nagel and M. Nagel Department of Biomedical Engineering, University of Stuttgart, Stuttgart, Germany Abstract— Every tenth patient in US and European hospitals suffers from preventable harm and adverse effects related to his or her care. As adverse events also carry a high financial cost, patient safety remains a major global priority. Often forgotten in discussions on the necessary actions to improve patient safety, clinical engineering is one of the major pillars for safe health care. Realizing the huge potential of contributing to the world-wide efforts to provide safer care, the clinical engineering community has accepted the challenge to take a lead in providing a safer environment for patients. Keywords— Patient safety, clinical engineering, Biomedea.

I. INTRODUCTION Patient Safety is a globally important issue in health care that the public has long been unaware of, though an increasing body of research from around the world consistently suggests that in any nation, regardless of the nature and quality of the health care system, a high percentage of hospital admissions may result in disease, injury or even death due to adverse events. These are all incidents and accidents that result in unintended harm to the patient by commission or omission rather than by the underlying disease or condition of the patient. Errors in treatment, nosocomial infections, communication problems, human and technical error, mistakes in patient management, as well as inadequate education and training of personnel are only some of the most frequent causes for adverse events. According to WHO, each time a patient is harmed by the health system, it is a betrayal of trust. These so-called adverse events are actually reverse events. Instead of advancing people’s health and well-being, medical errors send them backwards, causing more harm than good [1]. Studies in a number of countries have shown rates of adverse events ranging from 3.5% to 16.6% among hospital patients in industrialized countries. An average of one in every ten patients admitted to a hospital suffers some form of preventable harm that can result in severe disability and one in every 300 patients even dies as the result of an adverse event. Added to the considerable human misery is the economic impact of adverse events. Several studies have shown that additional hospitalization, litigation claims, hospital-acquired infections, lost income, disability and medical expenses cost some countries between US$ 6 bil-

lion and US$ 29 billion a year. In developing countries and countries in economic transition the situation is even far more serious. WHO reports that 77% of all reported cases of counterfeit and substandard drugs occur in developing countries and that at least 50% of all medical equipment in many of these countries is unsafe or unusable. Quality health care should be safe, effective, patient centered, timely, efficient and equitable. Safety is a core principal of quality health care provision and a fundamental value of any health system. In 2005, the European Union even proclaimed in its Luxembourg Declaration on Patient Safety that “access to high quality healthcare is a key human right recognized and valued by the European Union, its Institutions and the citizens of Europe. Accordingly, patients have a right to expect that every effort is made to ensure their safety as users of all health services” [2]. In our world of highly complex health technology where new equipment as well as medical and surgical procedures are developed and employed at an increasing pace, safety in the health care system is substantially depending on the achievements and performance of biomedical and clinical engineering as well as medical physics. Clinical engineering is taken to mean the application of medical and biological engineering within the clinical environment for the enhancement of health care. A Clinical Engineer is a professional who supports and advances patient care by applying engineering and managerial skills to healthcare technology. Due to the increasing dependency of clinical medicine on highly sophisticated health technology and thus on complicated medical equipment, devices and information & communication technologies, the clinical engineer has become an essential connecting link between modern medicine and technology. His work is directly associated with patient safety. The International Federation for Medical and Biological Engineering (IFMBE), mainly through its Clinical Engineering Division, and the International Union for Physical and Engineering Sciences in Medicine (IUPESM), together representing more than 140,000 professional biomedical/clinical engineers and medical physicists in virtually all WHO member countries, thus constituting a unique pool of expertise on the subject matter of health technologies, have established close cooperation with the World Health Organization (WHO) for the purpose of advancing patient safety. The Federation is closely cooperating with WHO in

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the areas of health technologies, specifically policy and planning, quality and safety, norms and standards, technology assessment and management, education and capacity building within the broad context of improving health service delivery and health systems performance. IUPESM and IFMBE are resuming leadership and coordination of the global WHO activities for the improvement of patient safety in the areas of health technologies and education with regard to health technologies. II. WHO WORLD ALLIANCE FOR PAIENT SAFETY Primum non nocere – first do no harm! Under this motto, attributed to Hippocrates (ca. 460-370 BC), the World Health Organization (WHO) and its partners, including IFMBE and IUPESM, launched the World Alliance for Patient Safety on October 27, 2004, in Washington, D.C. The purpose of the Alliance is to advance patient safety by implementing a series of key actions to reduce the number of illnesses, injuries and deaths suffered by patients during medical treatment. The creation of the World Alliance took place two years after the Fifty-Fifth World Health Assembly Resolution on Patient Safety in 2002 called on Member States to pay the closest possible attention to the problem of patient safety and to establish and strengthen science-based systems necessary for improving patient safety and quality of health care, including the monitoring of drugs, medical equipment and technology. The resolution urged WHO to take the lead in developing global norms and standards, encouraging research, and supporting efforts by Member States in developing patient safety policy and practice. It is expected that its work will eventually lead to much greater long-term safety in health care. The impact of welldeveloped and well-applied strategies on patient safety is expected to include a dramatic decrease in adverse events in health care and a decline in expenditure in the order of billions of dollars of saved costs annually. To focus its activities, the Alliance is defining key initiatives, the so-called Global Patient Safety Challenges which aim to identify a specific patient safety topic for a two year program of action which addresses a significant area of risk relevant to all countries. The motto of the first challenge “Clean Care is Safer Care” (2005 and 2006) aimed at reducing the burden of health care associated infections by good hygienic practice, demonstrating at the same time that much can be achieved and lives can be saved by simple, inexpensive measures. The goal of the second challenge “Safe Surgery Saves Lives“, which is currently being implemented, is to improve the safety of surgical care around the world. Clinical engineering will contribute with regard to all aspects of technologies, technology assessment and manage-

ment, as well as training of medical personnel. IFMBE and IUPESM are aiming at developing the third challenge focusing on health technologies and education. IFMBE and IUPESM are supporting the World Alliance for Patient Safety through their participation in Alliance initiatives and events as well as through their own patient safety activities which include the organization of patient safety symposia, the participation in the World Standards Cooperation (WSC) Healthcare Technology Task Force, promotion of biomedical and clinical engineering research related to patient safety, health technology assessment and management, and educational activities including quality assurance measures with regard to patient safety. III. IUPESM HEALTH TECHNOLOGY AND TRAINING TASK GROUP

In parallel and as part of the activities of the World Alliance for Patient Safety, the newly founded Health Technology and Training Task Group (HTTTG) of the International Union for Physical and Engineering Sciences in Medicine (IUPESM) is dealing with the issue of patient safety as well. Health technologies, from the simplest health care systems to the most sophisticated, are viewed as the backbone of each country’s health services, a strong mesh which is one of the most fundamental prerequisites for the sustainability and self-reliance of health systems. According to the definition commonly used by WHO, these include drugs, devices, equipment, technical, medical and surgical procedures, the knowledge associated with them in the prevention, diagnosis and treatment of disease as well as in rehabilitation, and the organizational and supportive systems within which care is provided. Drugs, which belong to special subsets of health technologies, are not included in the work of the HTTTG. Medical and surgical procedures are within the scope of this program only with regard to devices, technical support and education. Included into devices and technical procedures are the information and communication technologies. Steadily increasing health care costs have reached crisis proportions in many countries and are coming under close scrutiny from governments, health-care providers, insurers and consumers. Efforts to contain these costs, or at least to slow their growth, have been largely unsuccessful as they continue to outpace growth in gross domestic product. Though often blamed for the cost explosion in the health care systems, the cost of medical devices is only about 28% of health care expenses in most countries and properly selected technologies can substantially increase the quality of health care and at the same time reduce the overall burden and cost of sickness and health care. Realizing these

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opportunities is one of the goals of modern health technologies. In spite of all efforts to make all health technologies available to all countries, an increasing number of countries still can not shoulder the financial burden of acquiring and maintaining all technologies that would be desirable and beneficial for the health care of their people. Therefore it is necessary to establish priorities based on available resources and the burden of disease, a rather complex task for which the World Health Organization together with the IFMBE has already developed methodologies and tools such as the WHO Integrated Health Technology Package (IHTP). One of the prerequisites to make proper use of health technologies is the existence of an appropriate, reliable infrastructure. In order to set up and/or maintain this infrastructure, centers for health technologies should be established as part of the health ministries or at least strongly linked to them. These centers should implement the national strategies and plans for the health technologies, oversee and guide the national health care systems and, where appropriate, regional health care centers with regard to the health technologies as well as collaborate and build partnerships with health-care providers, industry, patients’ associations and professional, scientific and technical organizations (WHO Resolution passed by EB120, 22-30 January 2007). Another important step in improving the quality of health care and patient safety through health technologies is to build up the necessary health workforce, i.e. medical physicists, clinical engineers and technicians, which is able to manage, maintain and operate the technologies and educate the users, i.e. physicians and nurses, in the safe and competent use of equipment and devices. The industrialized countries should help those countries who cannot afford to provide education and training for a sufficient health care workforce by offering educational support. The role of the IUPESM HTTTG, being borne by IFMBE and IOMP, is to help identify needs in health technologies and training for each cooperating country, to make recommendations for actions to satisfy these needs, and, as far as appropriate and possible, support the countries in the necessary actions. The Task Group will cooperate and coordinate its activities with the World Health Organization and participate in the maintenance and further development of the WHO Integrated Health Technology Package. The HTTTG will collaborate with other relevant national and international organizations, academic institutions and professional bodies which provide support to developing countries in the prioritization, selection, acquisition and use of appropriate health technologies which are, according to the WHO Health for All Series’ Glossary of Terms, methods, procedures, techniques and equipment that are scientifically valid, adapted to local needs, and acceptable to those who

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use them and to those for whom they are used, and that can be maintained and utilized with resources the community or the country can afford. The HTTTG will, in cooperation with WHO, organize workshops in participating countries together with the local Clinical Engineers and Medical Physicists as well as all other relevant professional groups, the health ministries, health care providers and political decision makers to evaluate the health technologies in the countries and to develop plans for the realization of appropriate infrastructures for health technologies. IFMBE and IUPESM are in the position to substantially contribute to the initiative to improve patient safety, specifically, but not limited to, the areas of medical devices and equipment, appropriate health technologies, management and maintenance of healthcare technology, access to medical devices and norms and standards, all areas where especially IFMBE has demonstrated significant involvement in patient safety matters in previous and ongoing cooperative projects with WHO, both in developing and developed countries. Medical device and equipment safety is comprehensively dealt with in a set of guidelines for improved management of physical resources in health care, including a software-based resource-planning methodology and management tool, the Integrated Healthcare Technology Package. The two organizations have the expertise, the resources, the research capabilities and delivery potential to tackle all patient safety issues related to health technologies, including assessment and management, as well as means to facilitate the access to medical devices and to aid the transfer of technology for developing countries. IFMBE is also active in the development and application of international norms and standards as essential tools to ensure the quality and safety of medical devices. IV. CLINICAL ENGINEERING ENHANCING PATIENT SAFETY Dyro lists safety as one of nine components of clinical engineering practice. The clinical engineer is well-versed in the following issues bearing directly upon patient safety [3]: systems analysis; hospital safety programs; accident/incident investigation; root cause analysis, healthcare failure mode and effect analysis; user error identification and reduction; risk analysis and management; hazard and recall reporting systems; vigilance and post-market device surveillance; device-device adverse interaction awareness; electromagnetic compatibility and interference; and disaster preparedness. The other components of clinical engineering practice, while not directly addressing safety, do affect secondarily the safety of the patient. They are as follows: health technology management, medical device service,

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technology application, information technology, standards and practices, education and training, research and development, and clinical facilities engineering. Adequate, high quality education and training within the hospital with subsequent certification are essential prerequisites for the ability of clinical engineers to significantly contribute to patient safety. Only certification can assure that clinical engineers have the necessary knowledge, abilities and experience. It is hard to believe that, nevertheless, even in the US and almost all European countries any engineer, in many cases even anybody without an engineering degree, can call him/herself a clinical engineer and resume responsibility for the health technology in a hospital – without any proof of the required qualifications and competencies. Pointing out this problem at the European Union Patient Safety Summit in London in November 2005, Prof. Nagel asked the 543 delegates from 56 countries who were European and national political decision makers, representatives of the medical and nursing professions, health care providers and hospital managers, to vote on the question whether certification of clinical engineers should become mandatory in Europe. He received an overwhelming 82% rate of approval. Only 8% of the votes were against mandatory certification. So the biomedical/clinical engineering community has a political mandate to move on towards implementing the programs and management structures for the training and certification of clinical engineers. Hand in hand with the regulation of the CE profession there must be the obligation for the hospitals to employ sufficient numbers of CEs. Such an obligation would make it necessary to substantially increase the capacity of clinical engineering programs and would give higher educational institutions the perspective for the introduction of new programs. The Bologna Process and the Europe-wide introduction of Bachelor/Master programs offer a good opportunity to do so at least in Europe. For the Europe-wide implementation of high quality, harmonized Biomedical Engineering programs, J.H. Nagel is currently coordinating the BIOMEDEA project that he initiated in 2005 and in which 83 European universities and 30 national and international societies are participating. The project aims at developing European guidelines for the harmonization and accreditation of biomedical engineering programs, reach a Europe-wide consensus on these guidelines and thus allow for the mutual recognition of degrees. It also aims at setting up European Protocols for the training, certification and continuing education of clinical engineers. The project has proven to be very successful. The established guidelines for accreditation have already been accepted throughout Europe and have been implemented in a number of countries as national regulations. The protocols are close to being finished.

J.H. Nagel and M. Nagel

Due to the global importance of clinical engineering education for patient safety, WHO and the IFMBE are cooperating with BIOMEDEA, including the organization of patient safety symposia with global participation. The results of the BIOMEDEA meetings found international recognition and consent, and as a result, certification of clinical engineers on the basis of the BIOMEDEA protocols is currently being implemented around the world under the coordination of the IFMBE. V. CONCLUSION Now that the awareness of the need for improved patient safety has been raised and the dimensions of the problem have been recognized, there are numerous steps taken all around the world to make health care safer. Biomedical and Clinical Engineering have joined forces with the WHO to help improving the safety of health care technology. Much has been done already, but still more remains to be done to make health care in all its facets safer for all patients in the world. A poll taken by the authors at the World Health Care Congress Europe 2007, showed that while 78% among some 600 participants thought that we have a patient safety problem in Europe (20% were not sure), and 91% agreed that all relevant stakeholders should work together to make patient safety a top priority in Europe, only 43% of those attendees associated with a hospital confirmed that their hospital has implemented a medical error reduction or other patient safety program.

REFERENCES 1. 2. 3.

World Alliance for Patient Safety (2006) A Year Living Less Dangerously. Progress report 2005. WHO 2006 The Luxemburg Declaration on Patient Safety at http://ec.europa.eu/ health/ph_overview/Documents/ev_20050405_rd01_en.pdf Dyro JF (2004). The Clinical Engineering Handbook. Elsevier, Burlington, MA Corresponding author: Author: Joachim H. Nagel Institute: Department of Biomedical Engineering, University of Stuttgart Street: Seidenstrasse 36 City: Stuttgart Country: Germany Email: [email protected]

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System for Tracing of blood transfusions and RFID P. Di Giacomo1 and L. Bocchi2 1

2

Center for Biomedical Research - University of Rome La Sapienza, Rome, Italy Dept. of Electronics and Telecommunications, University of Florence, Florence, Italy

Abstract— In a medical center for blood transfusions, the blood haversacks are prepared and identified by a bar code label which identifies, for type and destination, the blood material according to the required standards. The traditional information systems use rigorous methodologies to verify and to watch the haversacks until they are delivered to the nurses. Nevertheless, at this stage, the tracing of the blood material is no more rigorous with particular regard to the mode and timing to give it to the generic patient. This is because we have not automatic systems to verify modes and timing for administering to the patient. This paper describes an automatic system for tracking the delivery process from the transfusion center to the patient transfusion. The proposed tracking system is based on RFID tags in order to offer a basic subset of functionalities also in absence of network collection. Keywords— RFID, quality, blood-transfusion, automatic clinical tracing.

I. INTRODUCTION The quality management in blood transfusion service is concerned with every aspect of transfusion practice and applies to all activities of a blood transfusion service. It involves identification and selection of prospective blood donors, adequate collection of blood and preparation of blood components, quality laboratory testing and ensuring the safest and most appropriate use of blood/blood components [1]. A simple definition of quality is ‘fitness for a purpose’. In a blood transfusion service, the primary goal of quality is ‘transfusion of safe unit of blood.’ The objective is to ensure availability of a sufficient supply of high quality blood and blood components for transfusion with maximum efficacy and minimum risk to both donors and recipients [2]. Quality management can be achieved by adopting good manufacturing practice, good laboratory practice, good hospital practice and good clinical approach by establishing a comprehensive and coordinated approach of total quality management [3]. All those who are involved in blood transfusion-related activity must be aware of the importance of quality management for its successful implementation. To maintain a high level of performance in most of the laboratory techniques, it is essential to monitor the functioning of reagent, equipment, techniques and procedures in the labo-

ratory and finally to manage the administering to the patient in a correct and safe way [4]. Medicare regulations in fact and the guidelines of the Joint Commission on Accreditation of Healthcare Organizations require assessment of the appropriateness of transfusions by a hospital committee. A set of criteria maps for component transfusion review by nurses or technical personnel was designed, tested, and modified. The intent of this paper is to present a system, as described in the following, for the automatic tracing of the blood units administering to the patients allowing to the health care professionals of familiarizing with the concept of effective quality assurance in regard to blood use. Although evaluation of the appropriateness of transfusion therapy is now required by the Joint Commission on Accreditation of Health Organizations, health care facilities have little experience with this aspect of professional quality assurance. To this end, for example, the Committee on Transfusion Practices of the American Association of Blood Banks, in Arlington, has provided examples of indications and audit criteria for individual blood components and products and commented on areas of controversy surrounding their use. Audit criteria from different institutions may vary because of differences in local interpretation of the indication, different patient populations, and, in some instances, the availability of blood and laboratory services. Moreover, several approaches to the review of transfusion practices are discussing in relation to clinical settings and pertaining to particular blood components [5]. II. SYSTEM DESCRIPTION The functional principle of the system is based on the coupling of the each blood unit with a specific patient. Moreover, the system requires of identifying the health operators involved in each intermediate phase, from the delivery of the unit to the transfusion to the generic patient. All the phases of the operations are executed across optical character readers for bar codes (fixed or mobile) and of RFID tags to identify the patient and prescriptions. RFID tags are increasingly in use in several sectors of health care system [6,7,8], as the standard bar code labeling suffers of

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ome drawbacks (read-only, need to optical contact, limited amount of data). The major requisites which guided the design of the system are: • •

interoperability: the system needs to interface with any existing Hospital Information System (HIS) with a minimal effort safety first: often transfusion center operates in emergency situation. The system needs to take into account that some checks may be skipped due to an emergency situation.

Due to those requisites, the system has been designed in order to minimize the data transfer between different phases, by using RFID tags where essential data may be stored, and by designing the software in order to maximize usability and flexibility of check points. The resulting system is composed by almost independent modules, which may be connected to the current HIS without the need to create a parallel and overlapping infrastructure. The modular architecture permits to configure and to adapt the system to the health context. The structure of the system can be represented through four functional distinct phases: two of them (admission and prescription) are executed with a computer, while the other two, the monitoring and the tracking of the operations during the transfusion, use a mobile device. A major issue which arises during the design of a system based on mobile devices is the selection of a connection method which allows transmission of data to the system. An emerging possibility is the use of wireless connections, which may provide continuous network connection while the device is in use. However, the usage of a wireless network in a health care system is still controversial. Interferences of wireless network with the medical instruments are the major concerns in several situations, and many hospitals do not have, yet, a complete wireless network available. For this reason, we resorted to design a systems which does not rely on a continuous connection of devices with the informative system, by using the memory embedded in the tags to store essential information required to perform real time checks, while transmission of data to the main storage is performed off-line when mobile devices are connected to the wired network.

ceives from the HIS the essential data about the patient (name, used for visualization purposes, and any unique id used in the HIS to identify the patient). The module can be realized in different configurations, for example as a WEB application and as a connection library. The simpler configuration uses a WEB application which uses the software installed on the server of the system. The acceptance of the patients is made by a WEB page which allows to insert the personal data related to the patient (name, surname etc.) and to assign of an unambiguous ID. When the data are stored, the system activates the RFID reader to write the data of the RFID bracelet. The WEB interface provides also the possibility to store the data, allowing the research of the patients and the optional printing of the form for the transfusion. Alternatively, the same interface can be used to allow connection from a custom HIS, which may activate the module using a single http call. The library version is used when it is needs to directly interface with the HIS. The operator uses the existing system to make all the necessary operations for the acceptance of the patient. However, the existing program has to be modified in order to make the association of the patient to the RFID bracelet.

A. Patient admission

B. Prescription

Each patient, at check-in phase, is identified by a tag RFID with a bracelet. At the moment of the reception, the tag is coupled with the code of the patient. The coupling is valid until patient is dismissed. This procedure has been realized (Fig. 1) by using a tag writing module, which re-

Each blood unit is prepared in the laboratory according to the universal standards and it is identified by a bar code to guarantee the contained material. The proposed system does not affect the clinical procedures involving the transfusion center until a unit is prescribed to a patient. At the moment

Fig 1: Prescription and association of a blood unit to a patient

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of assigning the unit to the patient for the transfusion, the system associates the bar code of the blood unit to the code of the patient until the end of the transfusion. This is performed by labeling the unit with a removable RFID tag. The system receives from the HIS the unique identification number of the patient and asks the operator to read the bar code which identifies the unit. Both data are then written of the RFID tag, which is applied to the unit. The system may also be configured in order to require the identification of the operator which performs the association. This identification is made by a badge if it has a bar code, or with a selfadhesive RFID tag. The module for the management of the prescriptions is analogous to the module for the acceptance of the patients, and it can be used both as WEB version and as library version. The realization in WEB version doesn’t require the installation of the software on the PC of the center for the transfusions, but it requires the presence of a server. The WEB version presents an interface to search the patients on which it’s possible to identify the patient that has to receive the unit and then to identify an unambiguous code. The requirements of the system are the same of the acceptance module with the addition of a bar code reader. When the system is connected by means of a communication library, the association is made at the available information system level. At the end of the operation, the library will activate the tracking system to write the tag, providing to the library the necessary data (bar code of the unit and identification of the patient).

Fig 3: Prescription of the unit

C. Tracking The system may be optionally configured to require a complete tracking of each unit during transport and temporary storage in the ward, until the delivery to the patient. Tracking is performed by means of a mobile device, a palm computer, equipped with a RFID reader and a bar code scanner (see Fig. 3). When the unit is transferred from an operator to a second one, or placed into a storage device, the tracking module requires the identification of both operators, or of the operator and of the storage device by reading their badges, or a tag attached to the storage device. All information concerning the operation is stored into the palm, while the current operator that is in charge of the unit and any constraint on the treatment of the unit (e. g. maximum storage time) is also stored inside the memory of the RFID tag. When the palm is positioned in the cradle for charging, data is uploaded to a central database to store all the history of the movement of the unit. At the same time, the information which is required to validate the next operation is available in the RFID without the need for any network connection. If the tracking system identifies any problem in the correct unit handling (e. g. storage time has exceeded the maximum duration, or the operator does not corresponds to the one who is in charge of the unit) it does not block the process, but signals the problem to the operator, who must acknowledge the warning and decide how to act in consequence to the problem.

Fig 2: Tracking of the unit

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indeed, quality assurance which can be achieved by means of a tracking system needs to be combined with some degree of flexibility of the tracking method, in order to comply with the major requisite of the health care process, which is the safety of the patient, especially in emergency situations. A tracking system which proves effective and which is well accepted by the medical staff needs to tune its requisites to each situation, ranging from minimal tracking, but maintain the essential functions, in the emergency situation, to the more complete tracking during routine procedures, without any excessive interference with ordinary activities.

REFERENCES 1.

Fig 4: Transfusion

2.

D. Transfusion The most important step is the transfusion of the blood unit to the patient. This step is mandatory, and the system requires the identification of the unit, the operator (or the operators) and of the patient. The system may be configured to require a certain category of operators (nurse, physician, or both) to be present during the operation (see Fig. 4). In this situation, in addition to the warning messages which may occur, as described in the previous step, a mandatory check is performed on the correct matching of the patient and the blood unit. After the operation is completed, the system may also record any adverse effect which may occur. As described before, all data is stored in the mobile device, and it will be transferred to the database when the palm is connected to its charging base.

3. 4. 5.

6. 7.

8.

Dzik WH. Emily Cooley lecture 2002: transfusion safety in the hospital. Transfusion. 2003, 43:1190-1199 Food and Drug Administration. Center for Biologics Evaluation and Research. Bar code label requirement for human drug products and biologics. Rockville, MD: February 25, 2004. Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/04-4249.htm Dzik WH. Emily Cooley lecture 2002: transfusion safety in the hospital. Transfusion. 2003;43:1190-1199 Fridey JL. Standards for blood banks and transfusion services, Bethesda, MD: American Association of Blood Banks, 2003 Rossi ED, Simon TL. Transfusion in the new millennium. In: Simon TL, Dzik WH, Snyder EL, et al, eds. Rossi's Principles of Transfusion Medicine, 3rd ed. Baltimore, MD: Lipincott Williams and Wilkins, 2002:1-12 Glabman M. (2004) Room for tracking. RFID technology finds the way. Mater Manag Health Care. 13(5):26-8, 31-4 Becker C. (2004) A new game of leapfrog? RFID is rapidly changing the product-tracking process. Some say the technology--once costs drop--could displace bar-coding. Mod Healthc. 2004 Jul 12;34(28):38, 40 James JS. (2005) FDA, companies test RFID tracking to prevent drug counterfeiting. AIDS Treat News. (417):5-8

Author: Leonardo Bocchi , Paola Di Giacomo

III. CONCLUSIONS The proposed system is a cost-effective solution to the tracking problem in the health care system. In this case,

Institute: Street: City: Country: Email:

Dept. of Electronics and Telecommunications Via S. Marta 3 50139, Florence Italy [email protected], [email protected]

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BIOMEDEA Joachim H. Nagel Department of Biomedical Engineering, University of Stuttgart, Stuttgart, Germany Abstract— There is widespread recognition of the need for high quality Biomedical Engineering education, training, accreditation and certification throughout Europe. Many schemes are being developed or are awaiting implementation, but there has been little harmonization. The continuing national differences in the educational systems are a serious problem that can hinder and limit trans-national education, training, employment and cooperation. The BIOMEDEA project aims at changing this situation by establishing Europewide consensus on guidelines for the harmonization, not standardization, of high quality MBES programs, their accreditation and for the training, continuing education and certification or even registration of professionals working in the health care systems. Adherence to these guidelines, which ultimately should be recognized in all 45 Bologna signatory countries, will insure mobility in education and employment as well as proper management of health care technologies, an important aspect with regard to the necessary safety for patients. Targets for the dissemination of results will be the European universities, political decision makers at European and national levels, the European Accreditation Council as well as the accreditation councils of all European countries, European quality assurance and accreditation agencies, health care providers and students. Keywords— BME education, BME accreditation, CE certification, CE continuing education.

I. INTRODUCTION Though harmonizing the European education systems and making European education policies more dynamic is high on the list of European political priorities, there are strict regulations and limitations on what is possible and who can decide which way to go within the EU. The 1997 Amsterdam treaty [1] clarifies which activities of the European Commission in the area of education are allowed in cooperation with the member countries in order to reach the common goal of high quality educational systems in all regions of the EU. The treaty emphasizes the European dimension of education, but nevertheless insists on subsidiary, clearly limiting the power of the Union, and leaving full and unrestricted responsibility for the structuring of educational systems as well as for curricula with the individual member states. The responsibility of the Union is to support and supplement activities of the member states in the area of education. The treaty does, explicitly, not allow harmoniza-

tion of national laws and administrative procedures by unilateral decisions of any European entities. Thus, implementation of the European Higher Education Area cannot be decided or dictated by the European Commission, it can only be achieved by European bodies that include all member states and that are able to reach unanimous decisions. Therefore, the Bologna process, i.e. the realization of the European Higher Education Area through the consensus of all 45 Bologna signatory states, is very important and needs to be fully supported by the Medical and Biological Engineering and Sciences (MBES) community [2, 3, 4]. For this purpose, a Europe-wide participation project, BIOMEDEA, has been launched in 2004 by Joachim Nagel in cooperation with Dick Slaaf (University of Utrecht) and Jan Wojcicki (International Centre of Biocybernetics of the Polish Academy of Sciences) as well as colleagues from 32 European countries, aiming at contributing to the realization of the European Higher Education Area in MBES [5]. The project coordinates previously started initiatives, using the available synergies to facilitate the implementation of the European Higher Education Area in the field of Medical and Biological Engineering and Sciences for the benefit of the universities, the students and last but not least the European people. The project aims at establishing Europe-wide consensus on guidelines for the harmonization of high quality MBES programs, their accreditation and for the certification or even registration and continuing education of professionals working in the health care systems. Improved quality assurance of MBES education and training is a vital component and is also directly related to the issues of health care quality. It offers the advantages of providing confidence for the employer that the employee has the necessary education, training and responsible experience, and the reassurance for the user of the service, meaning the patients, that those providing the service are effective and competent. Adherence to these guidelines will insure mobility in education and employment, and improved competitiveness of the European biomedical industries. Thinking about how to realize the requests for employability, mobility, compatibility, and quality assurance, it becomes obvious that the most urgent issues in this context are to harmonize and to generate agreement on the recognition and transparency of qualifications, specifically on ac-

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creditation of educational programs, training, continuing education, certification of individuals and a regulation of safety-critical professions. II. ACHIEVEMENTS, TRENDS AND DEVELOPMENTS Several studies have been published on the recent changes in the European national educational systems in general which indicate mostly positive influences on the quality of education. Information on the post Bologna developments of education, training and accreditation in the area of Biomedical Engineering has been gathered in the IFMBE White Paper on the status of MBES in Europe, organized and edited by Joachim Nagel [6]. Information has been obtained about the situation and practice in 28 European countries and contains an overview, written by Joe Barbenel (University of Strathclyde, Glasgow, UK), attempting to compare and contrast the different national models. When looking at all the information it is necessary to bear in mind two important constraints. The field of Biomedical Engineering is changing and growing rapidly, which means that some of the information was out of date almost as soon as it was written. The sections on different countries also show the enormous national variability in both educational practice and nomenclature that makes comparison difficult. It is to be hoped that the implementation of the ideas and aims of the Bologna Declaration will lead to more consistency and simplicity in the future. BIOMEDEA, the European participation project preparing Medical and Biological Engineering and Sciences for EHEA, is moving ahead very successfully with its goal to harmonize MBES education and training in Europe. There have been three meetings so far that took place in Eindhoven (2004, http://www.bmt.tue.nl/biomedea), Warsaw (2005, http://hrabia.ibib.waw.pl/Biomedea) and Stuttgart (2005, http://www.biomedea.org) which dealt with Biomedical Engineering (BME) curricula, the training, certification and continuing education of clinical engineers, and the accreditation of BME programs in Europe. The Eindhoven meeting consisted of 4 workshops: 1. The Undergraduate Biomedical Engineering Curriculum, with the goals to delineate the core topics in biomedical engineering science that all BME students should understand, the biomedical engineering science topics, underpinning areas of BME specialization, and the critical skills expected of all undergraduate biomedical engineers. 2. The Biomedical Engineering Master Curriculum. The goals were to delineate at the graduate level intellectual underpinnings for the future of biomedical engineering,

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integration of the engineering sciences and modern biology, engineering opportunities in the hospital, and critical skills. 3. Educational methods and best practices. The goals of the workshop were to discuss educational methods and to illustrate best practices adapted to teaching biomedical engineers how to solve clinical and biological problems. 4. Training. The goal of this part of BIOMEDEA was to gather the information necessary to write a survey on BME/CE Training in Europe and to establish guidelines for the minimum requirements for the training of Clinical Engineers in Europe. The Warsaw meeting included workshops on: 1. Guidelines for the accreditation of BME Programs in Europe: why do we need them and what should they specify? The goal of the workshop was to specify the general requirements of the guidelines. 2. BME/CE training – a European training scheme, with the goal to establish a European Protocol for the formation and training of biomedical or clinical engineers working in a hospital environment. 3. BME core competencies and specializations that should be recommended in the guidelines for the accreditation of BME programs in Europe. 4. Guidelines for curricula, specifying a flexible framework of BME curricula as a guide for the accreditation of BME programs. 5. Basic competencies in engineering/science, biology and medicine and general competencies including “soft skills” as minimum output requirements for accredited BME programs. The Stuttgart meeting included workshops on: 1. Criteria and Guidelines for the Accreditation of Biomedical Engineering Programs in Europe. Agreement has been achieved with regard to Bachelor and Master Programs. It was discussed whether there should be an accreditation of PhD programs as requested by the Bologna countries. 2. European Protocol for the Training of Clinical Engineers. 3. European Protocol for the Certification of Clinical Engineers. 4. European Protocol for the Continuing Education of Clinical Engineers. 5. IFMBE International Register of Clinical Engineers, and 6. Patient Safety - Biomedical/Clinical/Hospital Engineering Providing a Safe Health Care Environment.

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The third BIOMEDEA meeting in Stuttgart in September 2005 featured an international symposium on an important issue of quality assurance in biomedical/clinical engineering: patient safety. The Symposium was co-sponsored by the University of Stuttgart and the International Federation for Medical and Biological Engineering (IFMBE). It was organized in cooperation with the World Health Organization (WHO) and endorsed by the European Alliance for Medical and Biological Engineering and Science (EAMBES). The meeting was dedicated mainly to the development of a European scheme for the certification and continuing education of clinical engineers and sought cooperation with the responsible bodies in other parts of the world including the American Institute of Clinical Engineering (ACCE) to establish international cooperation with the goal to achieve global harmonization of the education and certification of biomedical/clinical engineers. 81 European academic institutions participated in the first three meetings and as a result, there has been agreement on the Criteria and Guidelines for the Accreditation of Biomedical Engineering Programs in Europe [7] and a European Protocol for the Training of Clinical Engineers [8]. European Protocols for the Certification and Continuing Education of Clinical Engineers have been discussed and are currently being written. In order to realize the principles of the European Protocol for the Training of Clinical Engineers, ade-

quate structures for the management of the training scheme as shown in Fig.1 must be put into place. On general request by the participants in the first three workshops, three additional meetings are being planned for 2007/2008. III. FUTURE DEVELOPMENTS The expected results of BIOMEDEA will be a white paper on BME education, educational methods and best practices in Europe, protocols for the formation, training, certification and continuing education of clinical engineers in Europe, and guidelines for the accreditation of BME programs in Europe. The International Federation for Medical and Biological Engineering (IFMBE), the main sponsor of BIOMEDEA, will, in cooperation with WHO and as a part of the initiatives of the World Alliance for Patient Safety and the Global Alliance for the Health Workforce, set up a global registry of certified clinical engineers with the goal of international mutual recognition of certification, and strive towards making certification and/or registration of clinical engineers, based on the same criteria, mandatory everywhere in the world. This will substantially improve mobility of clinical engineers but will also contribute to increasing patient safety. Primary goal of BIOMEDEA remains, however, to prepare the BME European Higher Education Area and to find

Fig. 1. Structure for the management of clinical engineering training and certification in Europe.

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recognition by the national governments throughout Europe, the European Union and the European bodies that are the main players in engineering education and accreditation. IV. GLOBAL ASPECTS MBES is not isolated from the rest of the world in the European Higher Education Area. The BIOMEDEA meetings have attracted international interest and participation in its activities. Global exchange of experiences and harmonization of MBES education and training, specifically in the field of clinical engineering, does not only contribute to the mobility of students, teachers and those employed in the various MBES professions, but it also contributes to the improvement of the health care systems and specifically patient safety. Experiences gathered in these international activities will in the future permit to further develop the guidelines and protocols for biomedical and clinical engineering education and training for the benefit of the discipline and the well-being of the people not only in Europe.

ACKNOWLEDGMENT The BIOMEDEA project has been made possible by the valuable contributions of all participants and organizers of the workshops, and the generous support from many universities and societies/organizations.

REFERENCES 1. 2. 3. 4. 5.

6.

7.

V. CONCLUSION The evolving European Higher Education Area will substantially influence the development of medical and biological engineering and sciences. These developments will be beneficial to the biomedical engineering profession and to society as a whole. The biomedical engineering community must grasp this opportunity through focused national and European actions and cooperation with the relevant bodies.

8.

Treaty of Amsterdam, http://www.eurotreaties.com/amsterdamtext.html The Bologna Declaration of 19 June 1999, http://www.bolognaberlin2003.de/pdf/bologna_declaration.pdf From Bologna to Bergen, http://www.bologna-bergen2005.no/. ECTS User’s Guide, http://www.hrk.de/de/download/dateien/ECTSUsersGuide(1).pdf J.H. Nagel, Biomedical Engineering in a European Higher Education and Research Area, Lecture Notes of the ICB Seminars, International Centre of Biocybernetics of the Polish Academy of Sciences, Warsaw, pp. 11-35, 2002. J.H. Nagel (Ed), Biomedical Engineering Education in Europe – Status Reports, http://www.biomedea.org/Status%20Reports%20on%20BME%20in %20Europe.pdf Criteria and Guidelines for the Accreditation of Biomedical Engineering Programs in Europe, http://www.biomedea.org/Documents/Criteria%20for%20Accreditati on%20Biomedea.pdf European Protocol for the Training of Clinical Engineers, http://www.biomedea.org/Documents/European%20CE%20Protocol %20Stuttgart.pdf Corresponding author: Joachim H. Nagel Department of Biomedical Engineering University of Stuttgart Seidenstrasse 36 D-70174 Stuttgart Germany Email: [email protected]

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Biomedical Engineering Education, Virtual Campuses and the Bologna Process E.G. Salerud1 and Michail Ilias1 Department of Biomedical Engineering, Linköping university, Linköping, Sweden Abstract— Higher education in Europe can be divided into before and after the Bologna Declaration, the most revolutionary process in modern education. Biomedical engineering, an emerging “subject” during the last 40 years, strongly interdisciplinary, fragmented and lacking of international coordination, may benefit from this harmonization process. An early initiative such as BIOMEDEA has made a contribution through proposing biomedical engineering foundations for building a common curriculum among higher education institutions. A common curriculum would presumably contribute to student and teacher mobility, certification and accreditation and as a consequence promote increased international employability. The virtual campus action extends or adds values to already existing educational exchange networks such as Erasmus, important in student mobility and educational harmonization and recognition. A virtual education dimension is added to European co-operation, encouraged through the development of new organisational models for European institutions, promoting virtual mobility and recognition. Virtual campuses may have a possibility to bridge the gaps in national BME curricula all with respect to the action towards a consensus on European guidelines for the harmonization. The evaluation of the e-curricula is conformant with the roadmap of BME courses as defined by BIOMEDEA. Most courses are classified as second cycle courses on a Master level, supporting that studies in BME could be a continuation from cycle one. Learning environment and the students learning outcome, points towards a strong teacher-centred approach to learning. The transparency at all levels are low, a factor that might influence recruiting potential students to a programme, especially those students with working experience and an international background. To fulfil the Bologna Declaration and other steering documents for the higher education in an expanding European future there are still tasks to be solved regarding recognition, legalisation, pedagogical issues and employability looking for a harmonized solution. Keywords— Biomedical engineering, Bologna, harmonization, virtual campus

I. INTRODUCTION In 1999, the most paramount reform in higher education in Europe, took off with the Bologna Declaration. It was signed by 29 European countries in an action programme with a clear defined goal: “to create a European space for higher education in order to enhance the employability and mobility of citizens and to increase the international com-

petitiveness of European higher education”. To reach the goal a number of objectives [1] were specified: • • • • •

the adoption of a common framework of readable and comparable degrees the introduction of undergraduate and postgraduate levels in all countries, with first degrees no shorter than 3 years and relevant to the labour market ECTS-compatible credit systems also covering lifelong learning activities a European dimension in quality assurance, with comparable criteria and methods the elimination of remaining obstacles to the free mobility of students and teachers

Further a European Higher Education Area (EHEA) should be established by 2010, now involving more signatories, focusing on curricular reforms and quality assurance. The aim of the European Higher Education Area is to provide citizens with choices from a wide and transparent range of high quality courses and benefit from smooth recognition procedures. Biomedical Engineering (BME) constitutes a field where the need for harmonisation and comparability is readily seen. Although BME has been established within Europe for more than 40 years, it still has not managed to get recognition between European countries or internationally to this day. Shortcomings of funding opportunities, fragmentation of educational and research programmes, and a lack of international coordination between programmes are some of the unfortunate features characterising the field. II. BIOMEDICAL ENGINEERING EDUCATION A. Biomedical engineering as a subject Undergraduate degrees in BME have been granted for many years. As an emerging field, biomedical engineering has been an interdisciplinary field; in which specialization occur after completing an undergraduate degree in a more traditional discipline of engineering or science. Biomedical engineers are supposed to be equally knowledgeable in engineering and the biological sciences. Comparing already established programmes, no defined common core or all required fundamental courses or a proposed curriculum,

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although in many programmes traditional courses in biomechanics and systems physiology are quite common. A complete recognition and becoming a “subject” of its own is indispensable in BME and do not exist today but have to be defined in the near future [2, 3]. However, the lack of agreements at the course levels does not mean that there is no similarity at the content level. In countries such as US recognition or accreditation is solved by a thorough evaluation of the Accreditation Board for Engineering and Technology, Inc. (ABET), a very demanding procedure, necessary for a BME programme to exist and be esteemed. Following the Bologna process aims at creating convergence and, thus, is not a path towards the “standardisation” or “uniformisation” but instead ”harmonization” of European higher education. The fundamental principles of autonomy and diversity are respected, preserved and recognized. The field of BME is progressing rapidly into new areas, quite often fusioning different technologies and methods from many different domains. The BME domain demands the students to develop multidisciplinary skills and knowledge and a possibility for life-long learning. Therefore, embracing pedagogical renewal as a part of new or revised curriculum in biomedical engineering education has been demanded. Harmonization with the Dublin descriptors on programme level is therefore inevitable. [4] B. BIOMEDEA – defining the curriculum BME, this emerging and evolving field, was early recognized and dedicated special attention to become harmonized with the Bologna Declaration because of its diversity and lack of common curriculum. More than 200 higher education institutions in Europe already offer educational programmes in Biomedical Engineering at all academic levels, but without any international coordination of contents and required qualifications. A harmonization and accreditation project “BIOMEDEA” [5] was initiated by Joachim Nagel and strongly supported by the IFMBE society in 2001. The aim of the project was to establishing Europe-wide consensus on guidelines: • •

for the harmonization of high quality BME programmes, their accreditation and recognition. for the certification or even registration and continuing education of professionals working in the health care systems

Recognition among higher education institutions is an important factor in ensuring student and teacher mobility and accreditation has mostly impact on the transnational employability. To improve human health and quality of life it is of vital interest that the employer is confident that the

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employee has the necessary education, skill, training and responsible experience, and is capable of managing the technology served. The BIOMEDEA project published in 2005 guidelines in recommending programme modules spanning the BME curriculum. Modules were attributed to: • • • • • • •

BME foundations BME in-depth topics Mathematics Natural Sciences Engineering Medical and Biological foundations General and social competencies

With the recommendations of BIOMEDEA, IFMBE, their national member societies, higher education institutions and stakeholders are able to comply with international harmonization of higher education, to show transparency and recognition and support mobility for education, training and employment. C. Virtual campuses - EVICAB Virtual campuses: Mobility of students and teachers do not always imply physical transfer. Using Information and communication technologies (ICT), may contribute to the quality of education and training and to Europe’s progress towards a knowledge-based society. It may also have an impact on the harmonization of curricula and joint degrees. The eLearning Initiative and Action Plan, proposed by EU, encourage co-operation, networking and exchange of good practice at a European level. It also has the potential to realize the vision of technology serving lifelong learning. One action is the European virtual campuses and particularly the European Virtual Campus for Biomedical Engineering (EVICAB). A virtual education dimension is added to European cooperation, encouraged through the development of new organisational models for higher European institutions, the virtual campuses, creating virtual mobility and recognition. It will add values to already existing exchange programmes like Erasmus, Comenius, etc. The objective of EVICAB is to develop, build up and evaluate sustainable, dynamic solutions for virtual mobility and e-learning that, according to the Bologna process, [6] • • •

mutually support the harmonization of the European higher education programmes improve the quality of and comparability between the programmes advance the post-graduate studies, qualification and certification

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Virtual European curriculum in BME cannot be obtained without first evaluating the existing curricula to be compared with a new or existing e-curriculum with good possibilities to strengthen harmonization, recognition and quality assurance. The survey is based on the BIOMEDEA curriculum proposal, extending the latter into the virtual domain. The status report produced within the BIOMEDEA framework [7] showed that BME programmes are often offered in single institutes and therefore the programmes cannot cover all subfields of BME needed in education of highly specialized engineers and physicists. Therefore, Virtual campuses may have a possibility to bridge the gaps in national BME curricula all with respect to the action towards a consensus on European guidelines for the harmonization. Evaluation: The evaluation was conducted through a manageable survey involving as many higher education institutions as possible, found in Biomedical Engineering Education in Europe – Status Reports (ref BIOMEDEA) and a wider search on the World Wide Web (WWW). Basic course information was collected regarding number of existing courses and courses planned to run within the next couple of years. The major part of the survey was designed elucidating the degree of course compatibility to the Bologna declaration. The following general trends could be discerned: • • •

the course operative language is often the native language of the responsible university. the course most often belongs to the 2nd cycle of qualification. the ECTS credit system is widely adopted.

The BIOMEDEA definitions seem to apply to the contents of the surveyed courses to a certain degree. The results showed that • •

the majority of the foundations and modules of BME as defined by BIOMEDEA are covered by the pooled courses. still there is a need for defining other topics and descriptions not covered by BIOMEDEA.

The survey also included the most valuable resources for the support of student learning outcomes as judged by those offering the course. The following resources were pointed out in order of priority: • •

in most courses the tutors were stated to be the most important. students’ work, laboratory and demonstrations was highly valued.

E.G. Salerud and Michail Ilias

A majority of courses was, according to those who responded, subject of measures assuring course quality in practice. The most common measures are: • • • • •

feedback by students. internal quality controls at a university level. peer review and internal work at an institutional level. controls by external bodies. use of field expertise in an educational context, assuring the quality of teaching or tutoring. Transparency issues were also addressed revealing that:

• •

course outcomes are most often publicly available. The most frequent means of publication is the WWW. outcomes are as a rule directly delivered to the students, most often by means of handouts.

Finally, the survey tried to shed light on distance course benefits regarding life long learning and student mobility between countries. The results showed that: • •

few BME professionals take advantage of distance education in order to support their continuing education. there is a limited number of foreign students attending distance courses. III. CONCLUSIONS

In the EUA document “Trends IV: European Universities Implementing Bologna” [8] evidence is found that the two cycle implementation has been achieved at nation level in most countries. Positive reports are also available regarding the curricular reform focusing on the learning outcomes. The evaluation of the e-curricula is conformant with the report since existing and planned courses seem to cover the proposed roadmap of BME courses as defined by BIOMEDEA. Most of the courses are classified as second cycle courses on a Master level, supporting the existence of a first cycle, and that studies in BME could be a continuation from cycle one. Approaching pedagogical viewpoints and the students learning outcome, both on a programme and course level, the teacher-centred approach to learning is still dominating. However, students’ work, labs and demonstrations could in this context, supporting a more student-centred approach. All educational centres reported working with quality assurance issues on a local, department level. The routines for external quality assurance aren’t clear and some showed willingness to comply with the European Network for Quality Assurance in Higher Education (ENQA) directives but without a declared roadmap and lack of transparency.

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Biomedical Engineering Education, Virtual Campuses and the Bologna Process

The transparency at all levels are low, a factor that might influence recruiting potential students to a programme, especially those students with working experience and an international background. Virtual campuses are an added value to existing exchange networks for mobility of students and teachers. To fulfil the Bologna Declaration and other steering documents for the higher education in an expanding European future there are still tasks to be solved regarding recognition, legalisation, pedagogical issues and employability looking for a harmonized solutions.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.

ACKNOWLEDGMENT The project is funded by the European Commission under the program Education and Training

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THE BOLOGNA PROCESS at http://ec.europa.eu/education/policies/ educ/bologna/bologna_en.html Linsenmeier R.A. (2003) What makes a biomedical engineer? IEEE Eng. Med. Biol. Mag. Jul-Aug;22(4):32-38. MBES position paper at http://www.eambes.org/docs/MBESposition-paper-final.pdf Dublin descriptors at http://www.jointquality.nl/ Criteria for the Accreditation of Biomedical Engineering Programmes in Europe at http://www.biomedea.org/documents.htm EVICAB at http://www.evicab.eu/ Biomedical Engineering Education in Europe – Status Reports at http://www.biomedea.org/ documents.htm Trends IV: European Universities Implementing Bologna – http://www.eua.be/fileadmin/user_upload/files/EUA1_documents/ TrendsIV_FINAL.1117012084971.pdf Author: Institute: Street: City: Country: Email:

E. Göran Salerud Department Biomedical Engineering Linköping university Linköping Sweden [email protected]

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European Virtual Campus for Biomedical Engineering EVICAB J.A. Malmivuo and J.O. Nousiainen Ragnar Granit Institute, Tampere University of Technology, Tampere, Finland Abstract— A Curriculum on Biomedical Engineering is established to the Internet for European universities under the project EVICAB. The curriculum will be free access and available free of charge. Therefore it will be available worldwide. EVICAB will make high quality education available for everyone and facilitate the development of the discipline of Biomedical Engineering. Keywords— e-learning, biomedical engineering

(iii) Advance the post-graduate studies, qualification and certification. These practices will be developed, piloted and evaluated in the field of biomedical engineering and medical physics. Important goal is that these approaches and mechanisms for virtual e-learning can be extended and transferred from this project also to other disciplines to promote virtual student and teacher mobility and credit transfer between European universities.

I. INTRODUCTION Biomedical Engineering is a multidisciplinary field of science covering a large number of sub-specialties. All these are developing very fast. Therefore, for any university, especially for smaller ones, it is difficult to produce and update high quality teaching material in all aspects of the field. Globalization encourages the students to mobility between universities. The BIOMEDEA project facilitates this by harmonizing the study programs in European universities. Internet is more and more used as a platform for educational material and student administration. The use of internet makes the geographical distances to disappear. All this gives strong reasons to develop an education program on the Internet for the use of all European universities. This is the basis for the project: European Virtual Campus for Biomedical Engineering – EVICAB. II. EVICAB PROJECT EVICAB project is funded by the European Commission, Education and Training. The objective of the project is to develop, build up and evaluate sustainable, dynamical solutions for virtual mobility and e-learning that, according to the Bologna process, (i) (ii)

Mutually support the harmonization of the European higher education programs, Improve the quality of and comparability between the programs, and

III. EVICAB CONSORTIUM EVICAB is coordinated by the Ragnar Granit Institute of Tampere University of Technology. Professor Jaakko Malmivuo serves as Director of the project and Assistant Professor Juha Nousiainen as coordinator. The other partners are: -

Mediamaisteri Group Ltd, Tampere, Finland Department of Biomedical Engineering, Linköping University, Linköping, Sweden Biomedical Engineering Center, Tallinn, Tallinn University of Technology Institute of Biomedical Engineering, Kaunas University of Technology, Kaunas, Lithuania. Department of Biomedical Engineering, Brno University of Technology, Brno, Czech Republic.

EVICAB welcomes interested institutes to join as associate partners. This means that the associate partners may participate the main meetings and they will get all the relevant information and may use the EVICAB material even before it is in public use. We also hope that the associate partners active participate in producing teaching material to EVICAB. IV. IDEA OF THE EVICAB The fundamental idea of the EVICAB is that it offers a platform for Biomedical Engineering curriculum on the Internet. Teachers, who are experienced and recognized experts in their field, are encouraged to submit full ecourses, course modules and other teaching material to EVICAB. The material may include many different formats

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J.A. Malmivuo and J.O. Nousiainen

Fig. 21. Universities take one or more BME Courses or the whole

Fig. 1. EVICAB is built from the BME Programs of the partner universities

curriculum from the EVICAB to complete their study programs.

A-E. Other universities (X) may also contribute.

like video lectures, PowerPoint slides, pdf-files, Word files etc. EVICAB is not a university. The course and student administration continue in the universities as usual: The teacher, responsible of the course/study program, may select from the EVICAB courses for the BME curriculum of the university. The students study the course either as ordinary lecturing course with the EVICAB material supporting the lectures or the course may be partially or solely studied from EVICAB. The students, or anyone even outside the university, may study EVICAB courses to add their competence in Biomedical Engineering. The EVICAB has an Administrative Board which administers the EVICAB curriculum. The board accepts courses of sufficient scientific, pedagogical and technical quality. The board may also invite experts to provide course material to the EVICAB. Courses which apparently are of low quality, either out of date, lower quality than competing courses and not appreciated by the users of the EVICAB will be deleted. Active feedback from the users of EVICAB, both teachers and students, is essential. All this will be realized by utilizing a dynamical quality assurance system.

For teachers: -

teaching material and other resources e-learning methods support for e-course development

For the study programs: -

improved quality harmonization of the degree studies

General: -

model applicable also for other disciplines VI. MOODLE PLATFORM

In EVICAB the Moodle program has been selected to serve as platform for the learning environment and learning management. Moodle is an open source program and therefore suitable to the EVICAB philosophy of free access. Moodle is also very versatile program offering a vide variety of tools for various pedagogical and administrative tasks. However, other open source platforms may also be used.

V. THE ROLE OF EVICAB IN E-LEARINING In its completed form, EVICAB will have impact on all main levels of the education process: For students: -

virtual mobility e-courses

VII. INTERNET EXAMINATION Another successful innovation and application in our elearning activities has been the Internet examination. In the Internet examination the students make the exam in a computer class. This may be performed simultaneously

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European Virtual Campus for Biomedical Engineering EVICAB

in several universities. Therefore the students do not need to travel to the location there the course was given. The students open the Moodle program at the time of the examination and find the examination questions from there. We usually allow the students to use all the material available on the Internet. This requires that instead of asking “What is ...” the questions shall be formulated so that they indicate that the student has understood the topic and is able to apply this information. The only thing which is not allowed is communication with some other person via e-mail etc. during the examination. VIII. WHY TO PROVIDE COURSES TO EVICAB? EVICAB will become an important teaching and learning method only if it is available free of charge and worldwide. As a consequence, the learning material should be provided free of charge. Why experienced and competent teachers should provide such material without charge and without royalties? Acceptance of a course by EVICAB will be a certificate for quality. Worldwide distribution to all university students will give exceptional publicity for the author and his/her university. All this will facilitate the sales of traditional teaching material produced by the course author. This will also attract international students from other countries all over the world to apply to the home university of the material author. We already have experience which has proven these issues to be realistic. The Internet has dramatically changed the distribution of information. Distribution is world wide, real time and free of delivery costs. The technology also supports wide variety of attractive presentation modalities. All this ensures wide audience and publicity for the material on the Internet. For

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instance, the Wikipedia dictionary serves as a successful example of this new era of information delivery. On the basis of this publicity it is possible to create markets also for traditional printed educational material. IX. CONCLUSION In future, the teaching and learning will mainly be based on Internet. The ideas and the technology of EVICAB are not limited only for application on Biomedical Engineering but it may be applied to all fields and levels of education. EVICAB will be the forerunner and show the way to more efficient and high quality education.

ACKNOWLEDGMENT Financial support from the European Commission and the Ragnar Granit Foundation is acknowledged.

REFERENCES 1. 2. 3.

EVICAB at http://www.evicab.eu Moodle at http://www.moodle.fi/evicab/moodle/ Malmivuo J, Plonsey R (1995) Bioelectromagnetism. at http://www.tut.fi/~malmivuo/bem/bembook/ Author: Institute: Street: City: Country: Email:

Jaakko Malmivuo Ragnar Granit Institute Korkeakoulunkatu 3 Tampere Finland [email protected]

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How New and Evolving Biomedical Engineering Programs Benefit from EVICAB project A. Lukosevicius, V. Marozas Kaunas University of Technology / Biomedical Engineering Institute, research associates, Kaunas, Lithuania Abstract— Problems of new and evolving Biomedical Engineering (BME) programs in European universities are collated with the opportunities and benefits offered by the EVICAB project. Benefits of European Virtual Campus for Biomedical Engineering (EVICAB) for new course developers, administrators, teachers and students are presented and illustrated by examples.

virtual environment which EVICAB project is offering, illustrated by case examples. Those three parts define a presentation structure below.

Keywords—Biomedical engineering; programs; teaching; learning; virtual environment.

Problems of new BME education programs begin with the choice of proper course composition, curricula and content of courses. Program from one side preferably should meet high quality criteria for EU accreditation [2] and from another – should include good courses delivered by high level specialists. Since BME education is multidisciplinary and high technology based at the same time, a difficult problem arises to cover the program with sufficiently high level courses from all necessary disciplines. Small countries also those newly entered EU usually haven’t good experience in BME field, also there is lack of long term traditions and industries developed. Therefore programs usually suffer from the top-down fitting of program courses to the limited possibilities of teachers and teaching environment. This usually causes a creation of big variety of one-sided or too specialized programs of limited quality defined by local qualifications and facilities. Problems with good teaching materials including demos, interactive practical work, textbooks, and software are very essential for new programs as well. Facilities of libraries don’t cover the needs, specific problem is in post-soviet countries where books in Russian are present in libraries but are not practically readable for new-generation students. Therefore collaboration, mobility, virtual environment for program development are problems of vital importance. Apart of technological problems in a new program development a conceptual teaching and learning problems arise [9, 10]. BME is a field where special teaching and learning methods are necessity, since it covers complicated issues of physiology, anatomy, tissue engineering, bioelectromagnetism, biophysics, sensors and transducers, signal and image processing, visualization, modeling of complex systems, direct and inverse problems of 3D systems and so on. Constructionism and constructivism, social constructionism concepts promoting a self-construction of knowledge, sharing and brushing knowledge obtained within appropriate environment are conceptual problems to cope with [4, 7, and 8].

I. INTRODUCTION Although biomedical engineering educational systems have been under development for 40 years, interest in and the pace of development of these programs has accelerated in recent years [1]. This acceleration is a natural consequence of the rapid evolvement of biomedical engineering science, technologies and rising sophistication of the equipment used today in medicine and biology. The pace of development causes specific challenges both for new programs which are starting (especially actively in new European Union (EU) member states) and already established and long running programs which are seeking for better quality, modernization and international harmonization within EU. Today more than 100 universities and colleges offer education programs on BME in EU. Wide scope of education goals and multidisciplinary of BME as a field of science and technology makes it difficult to consolidate and harmonize education programs under certain international criteria. Therefore activities towards EU accreditation of BME programs has been taken [2,11]. Additional challenge for the education programs is high requirements of research and education unity outlined in a form of national science education standards (for example in USA [3]). Universities experience significant problems in keeping the appropriate level of multidisciplinary BME programs, especially at new program establishment and in initial stages of program running. Since one of the missions of EVICAB project is to create a favorable virtual environment for program startup and modernization, the aim of present paper deals first - with the problems which new and evolving BME programs are facing, second – with means and tools which EVICAB project offers for the problem solving, and third - with benefits of

II. PROBLEMS OF NEW AND EVOLVING BME PROGRAMS

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1126–1129, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

How New and Evolving Biomedical Engineering Programs Benefit from EVICAB project Table. 1. Classification and ranking of main problems for new and evolving BME education programs No.

Problem

1.

Curricula composition in accordance with EU criteria for BME programs

2.

Re-engineering of programs in accordance with Bologna process Covering of wide, multidisciplinary scope of BME program in sufficiently high level Lack of teaching materials, textbooks, demos, interactive labs Lagging behind rapid development of BME technologies in the world Requirements for entrance to BME master program: need for an appropriate flexible equalization courses Keeping research and education unity: translation emerging technologies to the studies Sharing efforts and resources in preparation of courses, especially advanced ones Balancing the core/fundamental courses with application and emerging technologies oriented ones Internationalization and mobility of students and teachers, recognition of credits Adaptation of program for life long learning and part time studies Introduction of modern teaching and learning paradigms – constructionism, problem orientation, self-evaluation etc. Need for advise, discussion and collaboration in course and program development Involvement of the best lecturers worldwide

3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

13. 14.

New program 5

Evolving program 3

2

2

4

3

5

3

4

4

4

2

3

3

5

3

3

2

5

3

4

2

3

2

5

2

4

3

Problem rating used in the table 1. 1 – practically no importance 2 - little importance 3 – significant importance 4 – high importance 5 – very high importance In big extent problems typical for new programs are also valid for not new programs which are seeking for update, modernization and accreditation in EU (shortly – evolving programs). Among them one can point on the transition to the Bologna process and leading decisions by Sorbonne Declaration (inclusive objectives and statements), Salamanca resolution and Prague follow-up meeting from 2001defined the two-cycle program [5]. This problem is

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particularly important for well established BME programs in German speaking countries. The list of main problems is presented in Table 1. together with approximate ranking of problem importance for new and evolving programs. Evidently, new programs experience main difficulties since in addition to the problems listed practical questions of management, rooms and other facilities, legal frame of program, motivation and involvement of staff should be solved simultaneously. Entirety of problems needs for appropriate environment for successful solution. III. METHODS AND TECHNOLOGIES FOR NEW PROGRAM SUPPORT BY EVICAB

The contribution possibilities of EVICAB project for new and evolving BME programs lies deep in the mission and philosophy of the project. Openness and inheriting evolvement of the project itself respond to the evolvement of dynamic BME discipline and to the corresponding study programs, especially new ones. Project suggests an open coordination method used widely in EU (one evident example is EU Lisbon strategy implementation) together with concrete assistance. Main methods and technologies used for support of new and evolving BME programs by EVICAB project are as follows (in brackets the corresponding problems from the Table 1 are listed): EVICAB project keeps in account the accreditation criteria for EU BME programs developed by BIOMEDEA project [2] concerning program course composition, curriculum and course content. New programs are oriented towards those criteria from the beginning and further path of evolvement towards future EU accreditation is supported. (Response to problems No. 1, 2, 10, 13). Project integrates multidisciplinary BME courses creating virtual environment enabling choice of necessary high level, especially advanced courses which are usually not affordable for new program organizers due to lack of specialists, experience and facilities and other practical reasons. In many cases this is a chance to fill painful gaps in program influencing overall quality of the program. (Response to problems No. 3, 4, 7, 14). Advanced teaching and learning concepts and technologies available in MOODLE environment [4,6] and beyond [7] including problem orientation, self creation of knowledge structures, interactivity, self - assessment, internet examination are offered together with implementation examples in particular EVICAB courses. (Response to problems No. 5, 7, 12).

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Teaching and learning materials including e-Books, interactive models, demos, textbooks and other information is offered thus covering the painful lack of teaching resources for new BME programs and for programs seeking for update. (Response to problems No. 4, 5, 8). Flexibility of the virtual learning environment (VLE) used by EVICAB makes translation of research advancements and emerging technologies in the teaching and learning process easier, due to the openness, effective technologies for course update and involvement of best competences both in research and education. (Response to problems No. 3, 7, 9). Creating an environment for sharing efforts in development programs and courses. Since advanced course development is expensive and in many cases not affordable by national universities, especially for new members of EU, sharing of efforts and competences offered by EVICAB is of vital importance. The environment creates possibility to contribute for all participants and use the best competences wherever they are in EU. (Response to problems No. 3, 7, 10, 13). Virtual European campus for BME is a favorable environment for internationalization both of program and course development as well as teaching and learning. Open discussions, encouragement of contributions in course development for teachers, as well as mobility and course choice possibilities for students, environment of communication are supported by EVICAB. New programs especially in small countries are accepting little number of students (1020), therefore communication is vital. (Response to problems No. 10, 13, 14). Generally speaking new program developers and students are supported by EVICAB in several ways simultaneously: conceptual, methodical, technological, and teaching material supply. Complexity and openness makes EVICAB an evolving environment favorable for absorption of new findings and developments whenever they occur. IV. RESULTS, BENEFITS AND CASE EXAMPLES Results and benefits of EVICAB project could be classified for developers, lecturers/teachers, students and administrators. A benefit gradually becomes more evident with the development of the project. Below will be presented those of benefits, which could be already illustrated by the case examples. Benefits for developers: Harmonization of the program and curriculum with EU accreditation criteria, Bologna process direction; filling the gaps caused by the lack of national competences with best internationally recognized courses provided by outstanding lecturers; improving local

course content by collaboration within the project framework, getting support in terms of teaching materials, methodical and conceptual advises, good practice examples. Project promotes the use of modern technologies and tools of course development. New BME master program has been started in Kaunas University of Technology (KTU) in 2003 and it was the first BME program in Lithuania. Developers experienced a lot of difficulties and problems, because specific experience in BME field was very limited in the country. EVICAB support here was essential. Project enabled to gain an experience in program shaping and modernization, application of modern teaching and learning methods, also made available valuable teaching materials – e-Book on Bioelectromagnetism opened for free use by prof. Jaakko Malmivuo, valuable support and supervising Lithuanian students by prof. Goran Salerud, and other participants of the project. Without this support of EVICAB the successful start and running of the program hardly would be possible. Benefits for teachers/lecturers: Gaining experience from colleagues and good examples; use of open teaching materials; possibility to concentrate and improve own competence in the favorite field of BME and relying on EVICAB courses when needed other competence; possibility to contribute to EVICAB by own course and materials; sharing efforts in update and development of new courses; participation in discussions; self-evaluation of course quality; gradual adaptation of course to BME accreditation criteria. Teachers in KTU started to use MOODLE virtual learning environment, aligned new courses on adaptive biosignal processing, biomedical engineering methodology, clinical engineering with accreditation requirements, prepared computer - aided interactive laboratory works and practices, developed virtual instrument laboratory. New teaching concepts – problem based approach, encouraging of selfconstruction of knowledge system by students are under implementation. In 2006 a self-evaluation report on the KTU BME master program was submitted to the national quality evaluation committee. Benefits for students: Increased possibility for best course choice; participation in distant lectures and webinars; access to the advanced learning materials, textbooks, demos, illustrations, models and interactive practices; possibility to take course and pass exam remotely thus saving money for travel; more easy contacts with foreign colleagues-students and teachers; better conditions for mobility; better knowledge and better adaptation of European labor market in BME; possible recognition of qualifications in EU. Quiz organized in KTU for BME master students had shown that students are in general for the use of virtual European campus offered by EVICAB, they like new teach-

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How New and Evolving Biomedical Engineering Programs Benefit from EVICAB project

ing and learning materials delivered remotely. Interactivity and friendliness learning of environment was welcomed and better career opportunities stressed. Students participated in remote pilot intense courses and lectures delivered by Finnish and Swedish lecturers and enjoyed good technical quality (sound, image, demos, slides) of lectures and seminars. Benefits for administrators: Saving financial and other resources in organizing and running BME program; ability to motivate staff to raise qualification and to self-assess quality of courses and delivery methods; more objective evaluation of programs using international context; approaching a possibility to accredit program in EU; possibility to involve best EU competences with minimal expenditures. KTU administration welcomes project support and encourages Biomedical Engineering Institute to start a new bachelor program on BME using the opportunity to gain benefit from EVICAB project. V. CONCLUSION Project EVICAB responds well to the needs and problems of new and developing BME programs. Openness for access and contribution and open coordination concept of the project, use of modern teaching and learning technologies makes it useful for BME education in Europe.

ACKNOWLEDGMENT The work is supported by EU EVICAB project. Authors appreciate support by project leader prof. J. Malmivuo, and by all project participants from Finland, Sweden, Estonia, Slovenia and Czech Republic.

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REFERENCES 1.

Harris TR, Bransford JD, Brophy SP. Roles for learning sciences and learning technologies in biomedical engineering education: a review of recent advances Annu Rev Biomed Eng. 2002;4:29-48 2. J.H Nagel,. Accreditation of biomedical engineering programs in Europe – challenge and opportunity. Engineering in Medicine and Biology Society, 2001. Proceedings of the 23rd Annual International Conference of the IEEE Volume 4, Issue , 2001 Page(s): 3898 - 3900 vol.4 3. National Science Education Standards: Research and education unity. http://books.nap.edu/readingroom/books/nses/html/ 4. MOODLE philosophy http://docs.moodle.org/en/Philosophy 5. Helmut Hutten Two-phase Biomedical Engineering Education Program: Engineering followed by Biomedical training http://www.bmt.tue.nl/archive/BMEcongress011101/Hutten.htm 6. EVICAB project web page: http://www.moodle.fi/evicab/moodle/ 7. Theory and practice of online learning, Anderson T., Elloumi F., editors. Online: http://cde.athabascau.ca/online_book/index.html 8. Challenge-based instruction in biomedical engineering: a scalable method to increase the efficiency and effectiveness of teaching and learning in biomedical engineering. Med Eng Phys. 2005 Sep;27(7):617-24. 9. William B. Wood Inquiry-Based Undergraduate Teaching in the Life Sciences at Large Research Universities: A Perspective on the Boyer Commission Report Cell Biol Educ. 2003 Summer; 2: 112–116. 10. Howard L. Adaptive learning technologies for bioengineering education IEEE Eng Med Biol Mag. 2003 Jul-Aug;22(4):58-65 11. Biomedical Engineering Education in Europe – Status Reports at BIOMEDEA http://www.bmt.unistutgart.de/biomedea/Status%20Reports%20on%2 0BME%20in%20Europe.pdf Author: Arunas Lukosevicius Institute: Biomedical Engineering Institute of Kaunas University of Technology Street: Studentu str. 65 City: Kaunas, LT-51369 Country: Lithuania Email: [email protected]

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Learning Managements System as a Basis for Virtual Campus Project K.V. Lindroos1, M. Rajalakso2 and T. Väliharju2 1

Ragnar Granit Institute, Tampere University of Technology, Tampere, Finland 2 Mediamaisteri Group, Tampere, Finland

Abstract— Learning management system has an important role in web-based education. Mediamaisteri Group is an expert company in web-based solutions for e-learning and provides the platform for EVICAB (European Virtual Campus for Biomedical Engineering) project. In the project the openness and free availability has been the fundamental ideas since the beginning. Moodle learning management system supports the idea. Moodle is an open source platform. Leaning management system has been modified for providing the needed tools for virtual campus project. Keywords— Learning management system, ICT, Moodle, Virtual learning environment

I. INTRODUCTION Learning managements system (LMS) has an important role in web-based learning and especially in virtual campus projects. Activities and modules provided by the LMS can be chosen so that it supports the learning process. European Virtual Campus for Biomedical Engineering – project the driving idea has been open access, open content and free of charge utilization of all the material in the system. Based on the idea the open source Moodle platform was chosen.[4] Moodle platform has been used as a basis for the courses and all education. In addition to this the platform has provided beneficial tool for project management and communication between partners. In this report some aspect concerning the usability of such learning management system in virtual education and in project management will been discussed. II. WEB-BASED MANAGEMENT A. Course Management The benefit of the open source platform in the EVICAB project has been the possibility to modify the platform based on the needs of the learning process and content. The education in EVICAB is based on the totally distant education, and combination of contact teaching and virtual lessons. The learning process has several aspects which have to be supported when there is no direct contact with the teacher. The first problem is to provide easy access and

appealing environment for the students to study. The layout and color schemes have been designed so that the usability of the platform is as easy as possible. The main focus of the student has to be in the content and not in the applicability for ensuring successful learning experience. This can be achieved by careful design of the platform. Second issue is to provide inspiring and interesting lecture material. In this context the applicability is once again the key issue. The content of the lectures have to be easily accessible in order to let the student to focus to the content and not on the applicability. The content providers and teachers are advised to use media that are not based on any particular format and can be opened in a web-browser. For instance in video lecture production the Flash format is supported by the learning management system by providing a Flash module. Other, text based material, should be implemented to tools provided by the platform if possible, to ensure the functionality of the resource. Tutoring and communication with fellow students are also supported by the platform. Internal message system and e-mail lists are used for non-synchronous communication. Chat, provided by the platform, can be used for synchronous communication. Very popular communication channel in EVICAB has been the discussion forums. Forums have been opened on the course pages for various topics. Students may add their comments and questions related to the given topics.[2] LMS provides various tools for teacher to create different activities for the students. These activities support the exercises, assignments, quizzes and other tasks given for the student during the course. Moodle has built-in student administration and enrolment system, which have been used in EVICAB for keeping the record on the visitors, students, teachers and other personnel. [2] B. Project Management Learning management system has not only been used for supporting the web-based education but has been used in EVICAB project management. Various tools such as communication tools have been beneficial for the project. Several sites have been created to support the project work and work packages. Project files can be shared and modified in

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1130–1131, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Learning Managements System as a Basis for Virtual Campus Project

cooperation between different institutes by using the tools provided in the platform. For creating all the forementioned tools without learning management system the project would not be possible. The role of custom made platform for the education has been very important in terms of the whole project. The approach in the project is that “The system will guarantee a sustainable learning environment and content, of which development is based on continuous dynamic peer and self evaluation and effective exploitation of information and computer technology”.1 For this approach the Moodle platform was considered as the best option. Open source and free software supported the idea of the EVICAB project. Continuous development world wide of the platform ensures the dynamically evolving and up-to-date system. It is important to have dynamical and developing management system for dynamical virtual campus such as EVICAB.

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educational purposes may be further discussed but the experiences in EVICAB project have been very positive.

ACKNOWLEDGMENT EVICAB, European Virtual Campus for Biomedical Engineering is funded by European Union. Mediamaisteri Group is a private company. Mediamaisteri Group is an expert company in e-learning and aims to support the processes of web-based learning. [3]

REFERENCES 1. 2. 3. 4.

EVICAB home page at www.evicab.eu EVICAB Moodle at www.moodle.fi/evicab Mediamaisteri Group at www.mediamaisteri.com Moodle organization at www.moodle.org

III. CONCLUSIONS Learning management system is a key factor in webbased education. In the EVICAB project the Moodle platform has been successfully used as an educational tool but also as a project management tool. The selected platform for

Author: Institute: Street: City: Country: Email:

Kari Lindroos Ragnar Granit Institute PL 692 Tampere Finland [email protected]

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The E-HECE e-Learning Experience in BME Education P. Inchingolo1, F. Londero1 and F. Vatta1 1

Higher Education in Clinical Engineering, University of Trieste, Trieste, Italy

Abstract— This paper focuses on the e-learning experience in BME education of E-HECE (E-Higher Education in Clinical Engineering), an integrated distance learning system for education in Clinical Engineering at the University of Trieste (Italy). E-HECE is oriented toward providing to remote students many of the valuable aspects of the live classroom experience that are essential for learning. E-HECE has proven its successfulness in providing convenience to students who can actively participate in a class, whether they attend in person (physically, by videoconference or by video-streaming), and in making also available to the students recordings on-demand of classes synchronized with the lecture’s didactic material on the E-HECE e-learning platform. The E-HECE system made its debut in its current final version in September 2005, and since then it has been extensively used by the 340 E-HECE registered users for all the 150 courses in the Clinical Engineering program which have been delivered up to now. Its use has grown beyond Clinical Engineering including also courses in the health management and medical fields. The expansion of E-HECE’s capabilities continues to extend its utility and power as a distance education system. Keywords— BME education, e-learning, Moodle, videoconference, clinical engineering.

I. INTRODUCTION Education in engineering and technology fields is dominated by traditional classroom lecture presentations [1]. This setting requires students to be physically present on campus at the time of the lecture, but benefiting from interaction with each other and the lecturer. While the overall presentation of most courses remains lecture oriented, many organizations make increasingly productive use of the Internet as an instructional tool to make available supplemental and/or complementary course-related material to students with an asynchronous access [2]. With the aim of combining the benefits of both of these two fundamental trends, the SSIC-HECE (Studi Superiori in Ingegneria Clinica – Higher Education in Clinical Engineering) of the University of Trieste (Italy), within its educational Program in Biomedical-Clinical Engineering, has proposed and designed an integrated distance learning system named EHECE (E-Higher Education in Clinical Engineering), able to provide students with the means to actively participate synchronously with live classes and/or asynchronously with recordings of the classes. As a matter of fact, postsecondary

educational institutions offering engineering and technology programs face increasing demand from a student demographic characterized by working professionals often seeking further training (to remain current in their field or expand their expertise) or additional certification (certificates, degrees) [4]. This holds particularly in the field of Clinical Engineering [5]. One demand of this demographics is access to courses outside normal teaching hours, and, increasingly, without requiring the student to be physically present but participating in a class from their home or place of work using a computer. This demand is also felt keenly in urban areas, where traffic congestion can make classes difficult to reach. E-HECE has been conceived to meet this demand from a growing student constituency at a cost comparable to classroom instruction. The challenge posed by this growing demand is how to provide these students with the essential qualities of being present in a live classroom lecture, delivered using the Internet. What features of the live classroom experience are (or are not) critical to learning? The simultaneous teaching of a set of students in separate locations, some together in a classroom with the instructor, results to be a strong exigency. Irrespective of their location, students should have a strong sense of participation in the ongoing class, and critical to this feeling is the ability to interact with the instructor and their fellow students. As the ability to receive spoken and graphical content (e.g., slides and any annotations made on them), and to originate audio and video, can be provided by any modern personal computer, this same ability, combined with a connection to the Internet, can offer students a strong sense of participation, only requiring infrastructure that is widely and cheaply available. Hardware and software are hence required that allow remote-location students to do the following: 1) receive the live classroom content at any location while being assured that they do not lag the originating class; 2) ask and respond to questions in a natural way, e.g., by speaking; 3) interact with each other during class, the equivalent of a student asking a neighbor a question. E-HECE was designed and developed to fulfill these needs and to have the following benefits: 1) Being convenient for students, providing students with the ability to participate synchronously in a live class experience, not simply hear and see the classroom presentation, and also providing a recording of the class for future playback; 2) Being convenient for instructors, mini-

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mizing change in lectures’ presentation style; 3) Being conservative in capital and operating costs, as E-HECE requires no special hardware and minimal specialty software and can operate comfortably on configurations that are, by today’s standards, quite modest. These goals, and how E-HECE meets them, are discussed in more detail below. Technical details of E-HECE components and their operation appear in the next section, followed by a discussion of experience using E-HECE over the last years. II. THE E-HECE SYSTEM This section is organized as follows. First, the SSICHECE background history is briefly outlined to give the rationale for the choices that have been made in E-HECE system’s design. Then, the E-HECE system structure is described, with its videoconferencing and streaming facilities and the e-learning platform with the systems implemented for management of students activities, courses, exams and related safety procedures. A. The SSIC-HECE background The University of Trieste has a long tradition in the development of data and multimedia communication networks begun in 1988 with the First Biomedical Network of Trieste (RBT). From this starting point a strong activity in distanceeducation, health telematics and telemedicine has been developed. Since Academic Year 2003-2004, an extensive e-learning experience has been started at the University of Trieste for the total on-line fruition of the first level “Master in Clinical Engineering” (MIC-MCE) and of the International “Specialist Master of Management in Clinical Engineering” (SMMCE), activated within SSIC-HECE. The MIC-MCE and the SMMCE Masters have been formally activated within the Central European Initiative (CEI) University Network and they have been instituted as a transformation of the post-graduate Specialization School in Clinical Engineering, which has been active for 12 years as unique point of reference for education in clinical engineering in Italy and also widely recognized in Europe. Given the growing student constituency and demand, since Academic Year 2004-2005 also the Magistral Laurea Degree in Clinical Engineering (LSIC), a two-year graduate program, has been included in this e-learning experience. SSIC-HECE students are very often personnel already working in hospitals or in healthcare services’ companies either in Italy or in Europe and need therefore distancelearning cooperative instruments.

B. E-HECE videoconferencing and streaming The SSIC-HECE lessons are held in Trieste and simultaneously, by means of multi-video-conference, in many other distributed classrooms located in a number of peripheral sites (University Roma Tre, Polytechnic of Turin, IRCCS San Matteo of Pavia, Institute of Biomedical EngineeringCNR in Padova, IRCCS Casa Sollievo della Sofferenza in San Giovanni Rotondo (FG), Universities of Graz, Maribor, Rijeka and Zagreb). Multi-video-conference actually creates a multiple virtual classroom in which students from the different sites can fully interact with the teacher holding his/her lesson from one of these distributed sites or from another one, asking for questions, requests of clarifications, debates, discussion of practical experiences, etc. The classroom at the University of Trieste has been provided with fundamental videoconferencing facilities: a videoconference terminal, a projector/TV and a system of audio-diffusion with annexed mixer and microphone. The EHECE system has also been provided with a server installed for video distribution (streaming) in addition to a recording system integrated in the classroom with the videoconference system. This facility allows the students connected to the Internet with a PC to attend the lesson at the same moment in which the lesson takes place. A tool for production, synchronization and publication of multimedia contents has been designed and implemented to automatically obtain an electronic lesson complete of teacher’s audio-video and lesson’s slides, synchronized one by one, to be distributed on the Internet both live and on-demand, with a graphical output shown in Fig. 1.

Fig. 1 Snapshot of the system’s interface appearance with synchronization of the lessons slides with the video recorded during the lesson

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C. E-HECE e-learning platform The analysis of the characteristics of a suitable e-learning platform for E-HECE has been performed pointing out the required characteristics in both administration and courses area. The Moodle suite showed up as the best solution for the easiness of management and of system’s configuration [5-6]. An appropriate table for users list has been created in Moodle’s database with users’ main personal data. After certification on the platform, students can insert other personal information into their profile, as their photo, the personal home page, phone numbers, address, nickname for the used messaging systems etc. For the purpose of personalizing the access of each student to the platform, the Moodle’s registration procedure has been used, consisting of creating a registration table to enable accounting to the courses chosen by the single user. At the user’s first access to the platform, the system performs a control of existence of the user in users table and student’s data are uploaded with student’s registration profile for access to the courses according to the registration table. Fig. 2 shows a snapshot of the E-HECE homepage, with the links to the courses, links to lessons timetables and exams, contacts to secretariat, courses calendar, information about special events and general news. In addition, for each course, students can enter their name for examinations in a certain exams’ sessions thanks to Moodle’s “choice” function. Fig. 3 shows an example of a course’s module in the platform, with the links to the available lessons, identified by date, time, teacher and the lessons’ didactic material. The “Forum” section constitutes an information exchange section among the students attending a course and the teacher of that course.

Fig. 3 Example of a course in the platform E-HECE administrators can access each student’s profile and recall the activity report, visualizing the student’s complete activity, or the activity pertaining to a specific day on the entire platform, or the activity pertaining to the specific course. Teachers can monitor only the activity of the students enrolled in their courses. Given the data managed by the E-HECE platform, a twofold backup system has been also implemented, with a first weekly backup procedure according to Moodle’s platform functionality and with a second safety procedure executed at Operative System level of daily backup. III. E XPERIENCE WITH E-HECE

Fig. 2 Snapshot of the E-HECE homepage.

The E-HECE system made its debut in its current version in September 2005. Since then it has been extensively used for all the SSIC-HECE courses of the Biomedical-Clinical Engineering Program of the University of Trieste, serving a total student population of about 340 students in 150 courses. The actual set of students attending the courses has been observed to vary through the semesters. Some students attended live classes and then preferred to enroll in the E-HECE section of a course but the converse also occurred, as the nature of the classes is such that a student who attends one class online can easily attend the next one in the physical classroom. Students consistently rate highly the value of the lessons recordings; reasons include the ability to time shift a lecture to fit better with their schedule, to be able to handle interruption in cases where the entire lecture time cannot be allocated and the ability to re-play part of a lecture to review a particular topic. Fig. 4 shows some statistics on the E-HECE system from which the intensive use of the courses can be appreciated.

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Fig. 4 Example of report of the monthly history of visits to the E-HECE system for January 2007 (top) and statistics for country (bottom) IV. CONCLUSION This paper has described E-HECE, an integrated distance learning system for education in Clinical Engineering. EHECE is successful in providing to distance students many of the valuable aspects of the live classroom experience that are essential for learning, participating in a class, whether they attend in person (physically, by videoconference or by video-streaming), and in making also available to the students recordings on-demand of classes synchronized with the lecture’s didactic material on the E-HECE e-learning platform. It imposes little or no change in the way class presentation material is prepared, and mastery of the technology for teaching is very easily accomplished. E-HECE is extensively used in its final version since 2005, growing to a student community of over 340. Its use has grown beyond the clinical engineering courses, where it was first used, to include courses in the management and medical fields. The expansion of E-HECE’s capabilities continues to extend its utility and power as a distance education system.

ACKNOWLEDGMENT Work supported by SSIC-HECE, University of Trieste and by the CEI University Network.

REFERENCES 1. 2.

3. 4.

5. 6.

Pence HE (1997) What is the role of lecture in high-tech education? J Educ Technol Syst, 25:91–96 Waits T and Lewis L (2003) Distance education at degreegranting postsecondary institutions 2001–2002 National Center for Education Statistics, Washington, DC, Tech. Rep. NCES 2003-017 Wilson J (2003) After the fall: The lessons of an indulgent era Ann Conf Distance Teaching Learning, Madison, WI, Aug. 13–15 Inchingolo P et al. (2004) Integrated distance learning in biomedical sciences and engineering: the experience of the Higher Education in Clinical Engineering in EuroPACS-MIR 2004 in the Enlarged Europe, P. Inchingolo & R. Pozzi Mucelli (eds), EUT:435-438 Graf S and List B (2005) An evaluation of open source elearning platforms stressing adaptation issues Proc Fifth IEEE Int Conf Adv Learning Technologies, 3 pp. Colace F, DeSanto M and Vento M (2003) Evaluating on-line learning platforms: a case study Proc. 36th Hawaii International Conference on System Sciences, Hawaii, USA, 2003 IEEE Press Author: Institute: Street: City: Country: Email:

Paolo Inchingolo SSIC-HECE Via Valerio, 10 Trieste Italy [email protected]

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Web-based Supporting Material for Biomedical Engineering Education K. Lindroos, J. Malmivuo, J. Nousiainen Ragnar Granit Institute, Tampere University of Technology, Tampere, Finland Abstract— European Commission funded virtual campus project EVICAB (European Virtual campus for Biomedical Engineering) was launched in January 2006. The idea is to develop a virtual environment for students to study biomedical engineering by means of e-courses. The transfer from contact teaching to e-courses gave rise to a need for web-based learning material. In order to face the challenge a new project was launched in Ragnar Granit Institute to produce video lectures and other supporting material to the Internet. The produced material has been evaluated and implemented as a part of ecourses in EVICAB. Keywords— Biomedical Engineering, EVICAB, E-learning material, Video lectures

I. INTRODUCTION Virtual campus project EVICAB -European Virtual Campus for Biomedical Engineering was started in January 2006. The goal of the virtual campus is to establish virtual curriculum in Internet for students in biomedical engineering. EVICAB has been build on a learning management system and will provide web-based applications for providing study material, communication system, supporting material, and assessment tools. Ragnar Granit Institute in Tampere University of Technology is one of the contributors in this project. [1] Virtual campus will provide a variety of e-courses in the field of biomedical engineering. The transfer from classroom education to Internet-based education needs extensive study on available applications for supporting the process. The institute has provided learning supporting material in Internet for several years and used learning management system (LMS) for three years as an important part of the education. The experience in fore mentioned web applications has been vital in the process for providing all the course material in electronic form. For providing the needed material to EVICAB, a project was started for producing web-based learning material for supporting the students’ learning process. The education in virtual campus is based on courses with no or at least very little contact teaching. This fact has given rise to specific need for web-based learning supporting material. The different phases of the process will be discussed and different production methods will be presented. During the whole process the feedback and acceptance from students

has been the driving force. Every method and new approach has been evaluated and changes have been done accordingly. Biomedical Engineering is very technical discipline and for this reason the transfer from contact teaching into eteaching is not as simple as providing text files or online books for student but needs variety of tools for student to support their studying. Lecture material, supporting study material, online quizzes and exercises, peer communication, and online tutoring have now been implemented into the education. Especially the combination of lecture material and activation of the student during the study process have been carefully considered. The example course used in this study is Bioelectromagnetism by Professor Jaakko Malmivuo. II. MATERIALS AND METHODS A. Modeling Phase The process for creating e-learning material was started by evaluating the existing study material and comparing that to a student centered learning process model. (Fig. 1) The Model illustrates in very simple way the learning process. As an input for the process there are number of sources of information. In Internet education the text formats are the major source of information. Internet books and lecture material in electronic form is the basis for e-courses. The role of teacher is different in e-courses than in contact teaching. Teachers can be considered more as instructor or tutor for providing guidance and guidelines for students, how to study all the essential parts of the material. The role of supporting material is emphasized in the environment with no face-to-face contact with the teacher. Supporting material in this study is considered to be all the material provided in addition to the primary study material. All the sources of information are inputs to the study process. The most important role for supporting material in this process is to activate and instruct the student in such way that the course outcomes are achieved. Supporting material should also enable the student to do selfassessment during the process. Finally the outcomes of the study process will be evaluated. These outcomes can be exam, exercise answers, writ-

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Feedback

Teacher/Tutor

Outcomes

Student

Book Lecture Material

Study Process

Supporting material Assessment Fig. 1 Model for learning process

ten final report, learning diary etc. This is the way for the teacher to ensure that the objectives of the course have been reached. The model can be applied in various stages in a course. One particular section or chapter may be analyzed and the objectives for that particular entity can be monitored. Also the whole course may be implemented to the model, containing all the study material and applications. Once a student has studied all the material and generated the outcomes needed, the study process may be evaluated in correlation to the course objectives. The study process may be considered as an outcome in course design. In course design all the sections in the course has been represented. In the example course Bioelectromagnetism the sections have been divided into four: 1. Preparation, 2. Literature, 3. Video lectures, and 4. Internet Exam. In preparation section all the information on the course will be provided for the students. Contents of the course, prerequisites, learning material, contact information, and learning outcomes are all presented in the beginning of the course. Course literature will be the primary study material in the course. Internet book and lecture slides are provided. In addition to text-based material, video lectures are produced. Video lectures combined with quizzes and selfevaluation tests will support the learning process. Exercises have also been added in order to guide the students to focus on the facts that the teacher sees essential. At the end the Internet exam will test whether the objectives of the course have been achieved or not.

Different parts of the model in figure 1 have been supported in the learning environment. The communication between teachers and students are supported by the discussion forums in learning management system and via e-mail. Also the lecture material is available on the Internet in form of online book and written files in LMS. The most problematic part in the process of students learning in virtual environment for our case was how to support the learning process and how to provide such an interesting material that student feel comfortable for studying without face-to-face contact with the teacher. The idea of supporting material is to activate and stimulate students by providing interactive study material, quizzes for selfassessment, and exercises. Production of lecture videos in different format started the production of supporting material. Lecture videos were considered to be good format for mostly theoretical courses. First and perhaps the easiest way to provide lectures on the Internet is to combine PowerPoint slides with narration or with audio file. This method was first considered because of the simple and fast production. At the same time shooting of lectures was started. The captured video was combined with screen capture from the PowerPoint slides in order to provide more convenient way for students to follow the lectures. (Fig. 2) In this production type the lecture video and screen capture were recorded separately, edited and combined later by using SMIL, Synchronized Multimedia Integration Language. Hypermedia laboratory in Tampere University of Technology provided the SMIL code. The benefit from the custom made code was the possibility to change lay-out, table of content and size of any window in the video. These features are commonly considered quite limited in commercial versions. The next step was to embed interaction to the videos in order to maintain students’ interest and activate them during the process. The need for interactivity was met by adding

B. Implementation Phase The implementation of the study process model is a challenge for all the partners providing e-courses to EVICAB platform. For creating and evaluating different methods and applications that can be used in the implementation, a study has been launched.

Fig. 2 Screen capture from Bioelectromagnetism lecture video http://butler.cc.tut.fi/~malmivuo/bem/bembook/in/vi.htm

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quizzes and surveys to the videos. The video will be paused until student answers the quiz. In this way we provide a pause for the student to process the information and time to think the key issues in the particular section. III. RESULTS All the methods introduced in previous section were analyzed and evaluated. The method with only narrated pptfiles was not very well accepted by the student because of the lack of interactivity and it was considered even boring. The combination of screen capture and video on the other hand had very positive feedback. In the very first survey on the matter the feedback was 100 per cent (19/19) positive varying from average to excellent. The video lectures were also evaluated in relation to contact teaching and the result was surprising; in some cases the videos were preferred because of the possibility to rewind and pause. These features were especially valuable for those who have not fluent English or are easily distracted in classroom education. The negative feedback was related to usability of the videos. For watching the video students needed Real Player and one plug-in that was considered little awkward procedure. Due to the negative feedback on the file format the production was rearranged so that the outcome was in Flash format (.swf). Other feature which lead the production to Flash format was the possibility to add quizzes and surveys into the video. This feature was considered very important for activating students while they are watching the videos (Fig. 3) Production of Flash videos is at the moment in progress in Ragnar Granit Institute and no evaluation data has been analyzed yet but the experience has been promising.

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Due to the absence of contact teaching in e-learning the role of supporting material and especially self-assessment methods is important. In the example course in EVICAB, Bioelectromagnetism, for this purpose a set of quizzes has been created for every topic. Once a student has finished reading a chapter he/she has an opportunity test how well the concepts were understood. This gives the student opportunity to do self-assessment and get instant feedback whether some topics need more careful study or not. IV. DISCUSSION The challenge set in model for the study process has been taken seriously in EVICAB project. The format of all material is initially based on students’ feedback. The experience and feedback has been very positive on the lecture videos. The role of supporting material will be even more important in e-courses but its role also in contact teaching should not be neglected. In EVICAB course, Bioelectromagnetism, the students are advised to use the provided material so that they will follow the lecture videos and the e-book simultaneously and even try to find the answers to quizzes and exercises while reading. (Fig. 4) By combining the provided materials as an entity the student will be active participant of the lecture and will focus on the essential parts of the information flow. [2] The produced lecture videos are only one part of the ecourse. During the process many other aspects were taken into consideration. Both online and offline tutoring has been considered. In EVICAB courses students have possibility to discuss with the tutor or with peer students via discussion groups on specified topics or use chat for online communication. This is a way to provide guidance for students

Fig. 3 Screen capture from Bioelectromagnetism lecture video with quiz http://butler.cc.tut.fi/~malmivuo/bem/bembook/in/vi.htm

Fig. 4 Screen capture from Bioelectromagnetism lecture in EVICAB

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through Internet. In addition, peer communication will strengthen the feeling of solidarity. V. CONCLUSIONS European Virtual Campus for Biomedical Engineering project has a challenging approach to e-learning. The approach is to “develop a framework for a sustainable Internet-based virtual biomedical engineering curriculum” This task will be faced by developing and producing e-courses with up-to-date tools and content. [1] Ragnar Granit Institute is one of the contributors to the EVICAB curriculum. For this reason an extensive study and production of e-learning material has been started. Lecture materials are now available in electronic form. Also the importance of supporting material has been realized. The Internet-based tools are not only considered as tools for ecourses but they have also shown to be valuable asset in contact teaching. The current work at Ragnar Granit Institute has focused on video lectures and development of interactive study material. Videos have been accepted well by the students. The main benefits are the possibilities to rewind and pause if some concepts are not fully understood. Videos are also preferred in situations when students do not have time to attend the classroom lectures. The student may watch the lecture later at home. Quizzes and surveys are embedded to the videos for adding interaction, so that the student is more active participant of the lecture and not only passively listen to the teacher.

Video lecture production is a challenging task and has to be designed well before the shooting. The teacher has to be motivated and well prepared because the editing and reproducing the video is time consuming. If the topic of the course is developing fast, other production models should be considered. Changing the content of particular period of time in the video is inconvenient. The production methods represented here have worked well in Bioelectromagnetism course. The course is very well prepared and the professor has years of experience lecturing the material. Well prepared lecture slides ensure the successful video production and there has not been need for changing the content afterwards. The products of this study have been implemented to EVICAB -learning managements system. (www.moodle.fi/evicab)

REFERENCES 1. 2.

European Virtual Campus for Biomedical Engineering, http://www.evicab.eu/ Jaakko Malmivuo & Robert Plonsey: Bioelectromagnetism - Principles and Applications of Bioelectric and Biomagnetic Fields, Oxford University Press, New York, 1995 Author: Institute: Street: City: Country: Email:

Kari Lindroos Ragnar Granit Institute P.O. Box 692 Tampere Finland [email protected]

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Biomedical Engineering Clinical Innovations: Is the Past Prologue to the Future? P. Citron St. Paul, Minnesota, USA Abstract— The medical device industry, defined here as implanted therapeutic or restorative technologies, is roughly 50 years old. The first commercially available cardiac pacemaker to treat complete heart block was implanted in 1958 in Sweden followed by the first ball and cage prosthetic heart valve in 1960. From these tentative beginnings, medical device industry sales by U.S. companies were estimated to be $77 billion in 2003. Significant technology sectors now include mechanical and tissue prosthetic heart valves, cardiac pacemakers, implanted cardioverter-defibrillators to convert chaotic heart rhythms, cardiac re-synchronization devices to manage heart failure, vascular stents to treat occluded coronary and peripheral arteries, neurostimulation devices for certain central nervous system disorders, artificial joints and spinal implants for degenerative conditions, intraocular implants for cataracts, to cite representative examples. While financial metrics provide an indication of the direct economic impact of medical devices, a more relevant measure is the effect medical technologies have on reduction in patient morbidity and mortality, improved well-being, and increased quality of life. Illustrative of this, data compiled by the CDC shows mortality from heart disease has decreased about 50% between 1970 and 2003. A number of factors are collectively responsible, including lifestyle changes, availability of novel pharmaceutical agents, and more rapid initiation of treatment during a window of opportunity following onset of myocardial infarction. Unquestionably, the availability of improved heart valves, progressively more “physiological” rhythm management devices and coronary stents have also played an important role in the dramatic reduction in mortality. Technological innovations have made substantial inroads in treating the effects of diseases of the heart’s electrical conduction system which is responsible for setting appropriately the heart’s rhythm and contraction pattern, resolving valvular abnormalities that compromise the heart’s ability to meet the hemodynamic needs of the body, and reversing insufficient blood circulation to the heart muscle itself caused by atherosclerosis. Historically, medical devices have been mechanical or electro-mechanical. Although effective in the presence of serious disease, they lack the elegance of natural tissue and normal physiology. The emerging field of tissue engineering has already had a twofold effect on the advancement of medical devices. It has expanded knowledge of local biological phenomena in the presence of synthetic materials and influences. This has led to improved therapeutic device reliability, effectiveness, and performance. The second aspect has led to the development of so-called combination devices that consist of a drug plus device, or biological agent plus device to produce a desired tissue response. Arguably the first widely used example is the steroid-eluting pacemaker lead that became commercially available in the mid-1980s. This

combination of a device and drug reduced inflammatory response at the site of tissue/electrode contact and resulted in sharply lower short and long-term stimulation energy required to reliably stimulate the heart. This in turn led to extended device longevity. Other more recent examples are drug-eluting stents which improve long-term artery patency compared to bare metal stents and the combined use of bone morphogenic protein inserted in a metal “cage” to encourage and improve desired bone in-growth in spinal procedures. Tissue engineered products hold enormous promise. It is entirely reasonable to expect future products to begin clinical life as a “device” and then remodel into what is indistinguishable from normal tissue. This is the long held vision for a viable small caliber vascular graft and also for tissue repair that fully restores normal function in the presence of disease or trauma. Prognostications of future trends in biomedical engineering innovation would be incomplete without and examination of the environment in which the device industry operates. A number of factors adversely affect the climate for innovation. Although some progress has been made in certain aspects, the regulatory and reimbursement processes continue to lack transparency, consistency, predictability, and timeliness. Of particular concern is the notion of “good science creep” that poses seemingly reasonable questions regarding a proposed technology but which require overly and arguably unnecessarily complex clinical trials in order to secure regulatory or reimbursement approval. These seemingly reasonable clinical requirements can bias development of new technologies toward those that carry low risk, serve predictably large markets, and encourage investments in me-too next-generational technologies that incrementally improve current offerings, often at the expense of important breakthroughs. Associated costs and extended timelines have dampened the enthusiasm of the venture capital community to invest in device industry start-ups – a major source of innovations. Although the industry invests heavily in R&D (11.4% of revenue in 2002), the escalating cost of clinical trials and other mandated requirements are straining, if not reducing, investments in new technologies and innovation. The industry, clinical community, and also academia have not done enough to set expectations for medical implants. As a consequence, many patients have an over-expectation of the capabilities of technology. When performance falls short, the industry may experience a political, regulatory, and investor backlash. Related to this, patients may not possess the information and skills to properly assess risk. They may reject potentially life-saving technologies because of the remote possibility of device malfunction in the face of much greater disease-related risk. These factors, and others, must be more effectively balanced so the latent promise of biomedical engineering innovations can become reality. There

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Biomedical Engineering Clinical Innovations: Is the Past Prologue to the Future? is reason to be optimistic about the future. Patients and their families have come to appreciate how medical technologies have improved lives by restoring health and reducing suffering. There is now an expectation that new breakthroughs will emerge and that the future will be brighter than the past; that long-standing unmet clinical needs will be met.

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Author: Paul Citron Institute: Street: City: Country: Email:

University of California, San Diego 9500 Gilman Drive San Diego USA [email protected]

Keywords— biomedical engineering advancement, patients, trials

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Computer Aided Surgery in The 21st Century T. Dohi, K. Matsumiya and K. Masamune Graduate School of Information Science and Technology, University of Tokyo, Tokyo, Japan Abstract— Realization of new surgical treatment in the 21st century, it is necessary to use various advanced technologies; surgical robots, three-dimensional medical images, computer graphics, computer simulation technology and others. Threedimensional medical image for surgical operation provides surgeons with advanced vision. A surgical robot provides surgeons with advanced hand, but it is not a machine to do the same action of a surgeon using scissors or a scalpel. The advanced vision and hands available to surgeons are creating new surgical fields, which are minimally invasive surgery, noninvasive surgery, virtual reality microsurgery, tele-surgery, fetus surgery, neuro-informatics surgery and others in the 21st century. Keywords— computer aided surgery, surgical robot, three dimensional image, true three dimensional display, surgical navigation.

I. INTRODUCTION Surgical operations have developed in the method which skillful surgeon's hands and eyes are used. Therefore, it is very difficult to apply advanced technologies to surgical operations. To develop the new surgical fields of minimally invasive surgery, non-invasive surgery, virtual reality microsurgery, telesurgery, fetal surgery and others in the next century, it is necessary to use various advanced technologies; surgical robots, three-dimensional medical images etc. based on computer technology. Therefore, this new surgical field is called Computer Aided Surgery (CAS) [1]. Threedimensional (3-D) medical images provide the most recognizable information for medical doctors and advanced visualization for surgeons. Surgical robots function as advanced hands for surgeons. The advanced vision and hands available to surgeons are creating a new surgical environment. II. ADVANCED VISION Usually, medical images in a surgical field are used mainly for diagnosis before and after operation. Computer graphics technology visualizes 3-D structure of organs, vessels and tumors by information from the X-ray CT, MRI, echography and so on. The 3-D medical image as an advanced vision in CAS does not only remain in diagnosis, but is important also for the surgical navigation in a robotic

surgery. This surgical navigation can bring out a surgical robot's capacity. There are three kinds of the methods of a 3-D display; 1) pseudo 3-D display, 2) binocular stereoscopic display, and 3) true 3-D display. The true 3-D display produces a 3-D image in real 3-D space. As displays of this method, there are holography, integral photography (IP), and volume graph based on the principle of IP. As observation by this method is physiological, this observation does not cause visual fatigue. Absolute 3-D positions and motion parallax are given. IP projects 3-D models using a 2-D lens array called a “fly’s eye lens (FEL)” and a photographic film. Recently, a computergenerated IP has been developed by FEL and color liquid crystal display. It is named "Integral Videography (IV)" [2]. IV can display full color video. The volume graph and IV give absolute 3-D positions and they are much simpler than holography using interference of laser light. And they can project 3-D internal structure of a patient into a patient's body exactly and easily. Therefore they are very suiTable 3-D display for surgical navigation. Three-dimensional medical images during an operation by surgical robots are a very important. Especially true 3Ddisplay is the most important technology as well as robot technology for CAS in the 21st century. III. SURGICAL ROBOT [3] An advanced hand for a surgeon is one of the medical instruments and it is called a surgical robot or a therapeutic robot. As surgical robots for CAS, there are two kinds of robots, one is a navigation robot and the other is a treatment robot. By the way, if there is no electrical washing machine in the world, and researchers of robot are asked to develop the washing robot. Probably, the robot that imitates the wash work that man does is made. However everybody knows such a robot is not correct and everybody knows electrical washing machine is correct. The purpose of washing removes the dirt of clothes. The same thing is said about the surgical robot.

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1132–1133, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Computer Aided Surgery in The 21st Century

Surgical operations have developed in the method which skillful surgeon's hands and eyes are used. But surgical robots do not perform the same action as surgeons. In addition, the following thing can be said. • •

Many surgical operations are not suitable for performance by a machine. Machine that performs same action as a surgeon cannot treat better than a surgeon.

Therefore, surgical robots do not just imitate surgeon’s action, but it must be designed in consideration of the following points. • • • •

It should be designed corresponding to purpose of treatment. Mechanical mechanism must be suitable for a treatment by machine. It should provide better treatment than the current treatment provided by the surgeon's eyes and hands. It should make the most of the current knowledge and experience of the surgeon.

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REFERENCES 1

2 3

Dohi T et al. (1990) Computer Aided Surgery System (CAS) Development of Surgical Simulation and Planning System with Three Dimensional Graphic Reconstruction, 1st Conference on Visualization in Biomedical Computing, IEEE, pp 458. Nakajima S, et al. (1999) Development of a 3-D display system to project 3-D image in a real 3-D space, Proc. of 3D Image Conference'99, pp 4954. Dohi T (2004) Surgical Robots and Three-Dimensional Displays for Computer Aided Surgery, Recent Advanced in Endourology 6, Endourooncology, Springer, pp 15-26. Author: Takeyoshi Dohi Institute: Street: City: Country: Email:

University of Tokyo 7-3-1 Hongo Tokyo Japan [email protected]

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Innovations in Bioengineering Education for the 21st Century J.H. Linehan Department of Bioengineering, Stanford University, Stanford, USA Abstract— The National Academy of Engineering published a report titled The Engineer of 2020 [1]. That report suggests that, to meet the future head-on, we not only train our students to possess strong analytical skills but also to have practical ingenuity, be creative, have excellent communication skills, understand leadership, have high ethical standards, and be lifelong learners. Cognitive scientists have been suggesting that we change the educational process for the past 25 years. They opine that effective learning methods have shifted from concentrating on only developing skills and expertise to focus on students’ understanding of application and knowledge [2]. Bioengineering curricula are being created world-wide as new departments and programs are formed3. There are around 50 new undergraduate programs in the US alone. New curricula are largely being developed independently. As expected, bioengineering curricula have been focused on developing deep skills through a biology-infused engineering curriculum. In 2005, The Whitaker Foundation convened an international summit meeting to explicate ideas on the new discipline, bioengineering [3]. Diversity is good for the educational “ecosystem”. We can learn what works and what doesn’t by sharing information amongst programs. In the US, an informal organization has emerged, (BME-IDEA.org [4]), to promote teaching design, innovation, and entrepreneurship in the bioengineering curriculum. Design and problem-based learning are two examples of experiential learning processes meant to train students to be innovative in their approach to problem solving; that is, to become “adaptive experts”[1]. Biomedical engineering applications are particularly engaging to the students because they are “problems that matter”. My talk will

focus on two examples of learning methods that help students develop adaptive expertise are problem-based learning [5] and medical device design [6]. Keywords— diversity, teaching design, innovation, entrepreneurship

REFERENCES 1. 2. 3. 4. 5. 6.

The Engineer of 2020 – Visions of Engineering in the New Century. National Academy of Engineering, 2004 Bransford J (2007) Preparing People for Rapidly Changing Environments, J of Eng Edu. The Whitaker Foundation Biomedical Engineering Educational Summit Meeting, Lansdowne,VA., 2005 at http://bmes.seas.wustl.edu/WhitakerArchives/academic/ BME-IDEA.org. at http://www.stanford.edu/group/biodesign/bmeidea/ http://www.bme.gatech.edu/pbl/about.php http://innovation.stanford.edu/jsp/program/about.jsp Author: John H. Linehan Institute: Street: City: Country: Email:

Stanford University 318 Campus Drive Stanford USA [email protected]

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, p. 1142, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Multi-dimensional fluorescence imaging P.M.W. French Photonics Group, Physics Department, Imperial College London Abstract— Fluorescence offers many opportunities for optical molecular imaging and can provide information beyond simply the localisation of fluorescent labels. At Imperial we are developing technology to analyse and image fluorescence radiation with respect to wavelength, polarisation and, particularly, fluorescence lifetime, in order to maximise the information content. This talk will review our recent progress applying fluorescence lifetime imaging (FLIM) and multidimensional fluorescence imaging (MDFI) to tissue imaging and in vitro cell microscopy. Applying FLIM to autofluorescence of biological tissue can provide label-free contrast for non-invasive diagnostic imaging, as we have demonstrated in various tissues including atherosclerotic plaques, cartilage, pancreas and cervical tissue. FLIM and MDFI are also applicable to image intracellular structure and function for cell biology and drug discovery: hyperspectral imaging and FLIM can provide (quantitative) information concerning the local fluorophore environment and facilitate robust fluorescence resonant energy transfer (FRET) experiments while information concerning structure and rotational mobility may be obtained by applying polarisation resolution. Our most recent work includes high-speed and optically-sectioned FLIM for

automated imaging and live cell studies, hyperspectral FLIM for acquiring excitation-emission –lifetime matrices to distinguish different fluorophores and microenvironments and imaging of rotational correlation time, particularly applied to microfluidic devices. Excitation sources are a particular challenge for confocal microscopy and other FLIM modalities including endoscopy, owing to the complexity and limited spectral coverage of available technology. Increasingly we are exploiting ultrafast fibre lasers and continuously tunable ultrafast sources based on continuum generation in photonic crystal fibres for wide-field and confocal FLIM applications. Keywords— fluorescence, imaging, excitation.

Author: Institute: Street: City: Country: Email:

Paul MW French Imperial College Exhibition Road London UK [email protected]

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, p. 1134, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Nanomedicine: Developing Nanotechnology for Applications in Medicine Gang Bao Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA Abstract— In this presentation I will discuss the recent development of nanomedicine as an emerging field in the United States. In particular, I will give a brief summary of the US National Institute of Health (NIH) nanotechnology / nanomedicine centers established over the last few years, and present the bionanotechnologies being developed at the NIH nanomedicine centers at Georgia Tech and Emory University. The opportunities and challenges in developing nanomedince will be discussed.

II. MAJOR RESEARCH AREAS Table 1. NIH-funded nanomedicine centers in US Center Name

Lead Institutions

PI(s)

NHLBI Programs of Excellence in Nanotechnology (PEN) Nanotechnology: Detection and Analysis of Plaque Formation

Emory University and Georgia Tech

Gang Bao

Integrated Nanosystem for Diagnosis and Therapy

University of Washington in St. Louis

Karen Wooley

I. INTRODUCTION

Nanotherapy for Vulnerable Plaques

The Burnham Institute, San Diego

Jeff Smith

Nanomedicine is broadly defined as the development of engineered nano-scale (1-100 nm) structures and devices for better diagnostics and highly specific medical intervention in curing disease or repairing damaged tissues. Integrating nanotechnology, biomolecular engineering, biology and medicine, nanomedicine is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures with proteins and nucleic acids, the development and application of nanostructured probes and devices provides unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Realizing the great potential of nanomedicine, over the last two years the US National Institute of Health has established 24 national centers in nanomedicine, with a total budget of about $300 M over a 5-year period. These centers include four Programs of Excellence in Nanotechnology (PEN), funded by the National Heart Lung Blood Institute of NIH (NHLBI/NIH), eight Centers for Cancer Nanotechnology Excellence (CCNE), funded by the National Cancer Institute of NIH (NCI/NIH), and four Nanomedicine Development Centers (NDC), funded by the NIH Roadmap Initiative in Nanomedicine. Each of these centers involves a multi-institutional collaboration, and represents the state-ofthe-art in the development of bionanotechnologies and their application to medicine. Together, these centers form the cutting edge of nanomedicine in the US. The title, lead institution(s), and the names of the PI of each center are listed in Table 1.

Translational Program of Excellence in Nanotechnology

Harvard University Medical School

Ralph Weissleder

Keywords— nanomedicine, nanotechnology, molecular imaging, targeted therapy

NCI Centers for Cancer Nanotechnology Excellence (CCNE) Carolina Center of Cancer Nanotechnology Excellence

University of North Carolina

Rudolph Juliano

Center for Cancer Nanotechnology Excellence Focused on Therapy Response

Stanford University

Sanjiv Sam Gambhir

Center of Nanotechnology for Treatment: Understanding, and Monitoring of Cancer

University of California San Diego

Sadik Esener

Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology

Emory University and Georgia Tech

Shuming Nie and Jonathan Simons

MIT-Harvard Center of Cancer Nanotechnology Excellence

MIT and Harvard Medical School

Robert Langer and Ralph Weissleder

Nanomaterials for Cancer Diagnostics and Therapeutics

Northwestern University

Chad Mirkin

Nanosystems Biology Cancer Center

California Institute of Technology

James Heath

The Siteman Center of Cancer Nanotechnology Excellence

Washington University in St. Louis

Samuel Wickline

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1135–1136, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

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Gang Bao

NIH Nanomedicine Development Centers (NDC) Center for Protein Folding Machinery

Baylor College of Medicine

Wah Chiu

National Center for the Design of Biomimetic Nanoconductors

University of Illinois Urbana-Champaign

Eric Jakobsson

Engineering Cellular Control: Synthetic Signaling and Motility Systems

University of California, San Francisco

Wendell Lim

Nanomedicine Center for Mechanical Biology

Columbia University

Michael Sheetz

Nanomedicine Center for Nucleoprotein Machines

Georgia Institute of Technology

Gang Bao

The Center for Systemic Control of Cyto-Networks

University of California Los Angeles

Chih-Ming Ho

NDC for the Optical Control of Biological Function

Lawrence Berkeley National Laboratory

Ehud Isacoff

Phi29 DNA-Packaging Motor for Nanomedicine

Purdue University

Peixuan Guo

advances in developing nanostructured probes for molecular imaging, including the design, synthesis, characterization and validation of molecular beacons. I will also discuss the novel properties and functions of nanoparticle probes such as quantum-dot bio-conjugates and magnetic nanoparticles. These probes provide a new platform for molecular targeting and imaging in living cells and animals. Examples will be given on the applications of the novel imaging probes to basic biological studies such as living cell gene expression, and disease studies including cancer and cardiovascular research, and the detection of viral infection. The new challenges in nanomedicine such as the deciphering of engineering design principles and fundamental biology of protein nanomachines will be discussed. Author: Gang Bao Institute: Street: City: Country: Email:

Georgia Tech 313 Ferst Drive Atlanta USA [email protected]

In my presentation I will focus on the development and application of nanostructured probes. I will review recent

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Synthetic Biology – Engineering Biologically-based Devices and Systems R.I. Kitney Biomedical Systems Engineering, Department of Bioengineering, Imperial College London, London, Great Britain

Synthetic Biology is an emerging field that aims to design and manufacture biologically-based devices and systems that do not already exist in the natural world, including the re-design and fabrication of existing biological systems. The foundations of Synthetic Biology are based on the increasing availability of complete genetic information for many organisms, including humans, and the ability to manipulate this information in living organisms to produce novel outcomes. More specifically, engineering principles, including systems and signal theory, are used to define biological systems in terms of functional modules - creating an inventory of ‘bioparts’1 whose function is expressed in terms of accurate input/output characteristics. These ‘bioparts’ can then be reassembled into novel devices acting as components for new systems in future applications. Systems Biology aims to study natural biological systems as a whole, often with a biomedical focus, and uses simulation and modeling tools in comparisons with experimental information. Synthetic Biology aims to build novel and artificial biological systems, using many of the same tools, but is the engineering application of biological science rather than an extension of bioscience research. There is quite a close relationship between Synthetic Biology and Systems Biology. The basis of quantitative Systems Biology lies in the application of engineering systems and signal theory to the analysis of biological systems .This allows the definition of systems in terms of mathematical equations and complex models – often as individual functional blocks (i.e. transfer functions). Once a system, or part of a system, has been described in this way then Synthetic Biology allows the reduction of the system to parts (bioparts) whose function is expressed in terms of input/output characteristics. These characteristics are then presented on a standard specification sheet so that a system designer can understand the functional characteristics of the part. The parts are then entered into a repository. The parts defined in the repository can then be combined into devices and, finally, into systems. For example, in the same way that standard engineering devices, such as an oscillator, can be realized in the terms of fluidics, pneumatics and electronics, biologically based oscillators can now be realized in terms of protein concentrations2. Tolerances are built into the design of any engineering part, device or system to compensate for imperfections in the manufacturing. Bioparts tend to have wider tolerances than standard engi-

neering parts, so biologically-based devices are designed to accommodate such features. Synthetic Biology uses the classic engineering reductionist method whereby complex systems are built from defined parts and devices. In addition, the approach to the design of such devices and systems which has been successfully implemented is that of the Engineering Cycle. This is illustrated in Figure 1, below. The Engineering Cycle starts with defining the specification for the device or system which is to be designed and built. The next step in the process is to design the device or system on the basis of the specification. Frequently in engineering the design is then tested by extensive modeling. In the case of Synthetic Biology this is almost always an important step. As can be seen from Figure 1, modeling is followed by implementation, testing and validation. Synthetic Biology could revolutionize a number of fields of engineering. Materials are one example of a potentially important area. Here, Synthetic Biology involves the harnessing of biological processes (on an industrial scale) to produce new materials. In many areas of industry, for example the aeronautical industry, there is a pressing need to use materials that are very strong but, simultaneously, extremely light. In aircraft design if it were possible to significantly reduce the weight of the aircraft there would be immediate and major improvements in fuel consumption. The understanding and manipulation of the biological processes

Specification

Testing/Validation

Design

Implementation

Modelling

Fig. 1 The engineering cycle

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, pp. 1138–1139, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Synthetic Biology – Engineering Biologically-based Devices and Systems

that control the production of such materials, via Synthetic Biology, could result in the synthesis of a whole range of new materials. This would significantly change and invigorate several industrial sectors such as civil engineering, aeronautical engineering and the automotive industry. Biologically based electronics and computing are another important area. Biologically synthesized devices may be operationally many thousands of times slower than their electronic equivalents, but this may be an advantage if such devices are to be used to monitor biological processes (i.e. the time constants of the devices match the environment in which they are operating). We may well be at a similar point today to where the great industries of the twentieth century (mechanical, electrical, aeronautical engineering etc) were at the end of the nineteenth century - i.e. at the dawn of new era of engineer-

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ing. The biologically based engineering industries of the future will arise from the Cellular and Molecular Biology revolution which has occurred over the last fifty years. The engineering application of this new knowledge via Synthetic Biology will result in new industries that will have similar, if not greater, potential for enormous wealth generation. Author: Richard I Kitney Institute: Street: City: Country: Email:

Imperial College London Exhibition Road London United Kingdom [email protected]

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The Physiome Project: A View of Integrative Biological Function C.F. Dewey Department of Mechanical Engineering, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, USA Abstract— The Physiome Project comprises a worldwide effort to provide a computational framework for understanding human and other eukaryotic physiology. The aim is to develop integrative models at all levels of biological organization from genes to the whole organism. This is achieved via gene regulatory networks, protein pathways, integrative cell function, and tissue and whole organ structure/function relations. A key hallmark of the Physiome is that it covers many physical scales of description, from molecule-molecule interactions to whole cell behaviour to whole organ descriptions. This talk will stress the computational and semantic layers of the Physiome, the mathematical and logical “glue” that allows the various physiological scales to communicate and work with one another. The first knowledge domain is Ontologies. Ontology is a specific expression of known facts about the real world. Work on ontologies is being undertaken in order to organize biological data and knowledge at the different levels of the biological continuum. An additional and important component of this work is to facilitate easy and effective access to a range of databases, and to facilitate automated reasoning that can simultaneously extract information from many databases. We will illustrate how ontologies can be used to create and manage databases in an intelligent manner. Biology and medicine are replete with many Databases, and the physiome goes from information on the smallest scales such as genes and proteins to whole organs such as the beating heart. They have been designed to hold experimental data such as those from medical images and microarrays, and they have also been constructed to hold consensus information such as curated scientific “truth” about genes and proteins. A considerable amount of

work has been undertaken to integrate the meaning of different facts that appear in these different databases, but unfortunately that process today is very time-consuming and difficult. We will discuss how working first with the ontologies and then deriving the databases from them makes this problem much easier. The third leg of the Physiome has to do with quantitative prediction using explicit Biologically-Based Models. A number of markup languages, based on the XML standard, have been developed to describe these models, e.g. SBML, CellML and TissueML. The languages are designed to facilitate the encoding of models of biological structure and function in a standard format. The markup languages represent common semantic understandings which have been developed to greatly enhance the ability to share data and models. It is also possible to re-use parts of the more comprehensive models in new models – often being developed by other groups of workers. An example of this reuse is the Cytosolve system of shared solutions to biological pathways. Keywords— Physiome project, databases, markup languages Author: C. Forbes Dewey Institute: Street: City: Country: Email:

Massachusetts institute of Technology 77 Massachusetts Avenue Cambridge USA [email protected]

T. Jarm, P. Kramar, A. Županič (Eds.): Medicon 2007, IFMBE Proceedings 16, p. 1137, 2007 www.springerlink.com © Springer-Verlag Berlin Heidelberg 2007

Index Authors A Abbas, Abbas K. 385 Abbott, D. 26 Abramovic, Z. 453 Acampora, F. 762 Acampora, S. 762 Accardo, A. 78, 445 Accetto, R. 354 Akerman, S. 810 Alcaraz, R. 54, 90, 94 Alesch, F. 651 Alizad, A. 1021 Alvarenga, A.V. 1025 Amon, S. 178 Andersen, O.K. 669 André, F.M. 623 Anier, A. 554 Argenziano, L. 758, 1066 Arifin, A. 647 Armas, J. H. 313 Arora, V. 685 Arredondo, M.T. 558 Auersperg, M. 469 Azevedo-Coste, C. 654

B Bachmann, M. 210 Bajd, B. 365 Bajd, T. 262, 950, 954, 982 Bajic, D. 773 Bakker, J.M.T. de 42 Bao, Gang 1135 Baranov, V. 911 Bardorfer, A 965 Barea, R. 1038 Baretich, M. 1051 Barison, S. 194 Barlic, A. 249 Baroni, M. 847 Barraco, R. 919 Barrella, M. 932 Barthel, P. 38 Batiuskaite, Danute 606 Bauer, A. 38 Bauld, T. 1051 Baumert, M. 26 Belic, A. 478, 501

Belkov, S.A. 856 Bellazzi, R. 14 Bellomonte, L. 919 Beltrame, M. 723, 732 Benazzo, F. 238 Benca, Maja 357 Berdondini, L. 525 Berner, N.J. 190 Bertolini, Giovanni 977 Bester, J. 323, 332, 737 Bevilacqua, M. 932 Bianchi, A.M. 30, 473 Biffi Gentili, G. 752 Bifulco, P. 369, 426, 777, 789, 990, 1096 Bijak, M. 658 Bijelic, G. 654 Birkfellner, W. 834 Bisaccia, L. 758 Blas, J.M. 54 Blazun, H. 716 Blinc, A. 859 Bliznakov, Z. 928 Bliznakov, Z.B. 1092 Bliznakova, K. 923, 928 Bocchi, L. 1062 Boccuzzi, D. 426 Bocquet, B. 170 Bohanec, Marko 708 Bohinc, K. 903 Bojic, T. 482 Bojkovski, J. 338, 361 Bollmann, A 82 Bondarenko, S.V. 856 Boquete, L. 1038 Borean, M. 445 Bosazzi, P. 723, 732 Botelho, M.L.A. 319 Bottacci, D. 1102 Bouatmane, S. 843 Bouridane, A. 843 Bracale, M. 758, 762, 1066 Brai, M. 919 Bravar, L. 445 Brennan, T.P. 50 Brezan, S. 478, 501 Brezovar, D. 965 Brguljan-Hitij, J. 354 Bruno, P. 509, 513

Buchgeister, M. 313 Buchvald, P. 270 Bunce, S. 473 Burdo, S. 390 Burger, H. 943, 965 Burger, J. 875 Busayarat, S. 822 Butolin, L. 943 Butti, M. 473 Buyko, S. 346

C Cabral, J. 505 Cadossi, R. 10 Cagy, M. 492 Calani, G. 752 Calil, S.J. 319, 1085 Campbell, R.I. 969 Capek, L. 270 Carrozzi, M. 445 Casar, B. 887 Castrichella, L. 745, 749 Cavallini, Anna 152 Cemazar, M. 465, 469, 582, 586, 589, 602, 618 Chen, C.H. 242 Cerutti, S. 30, 473 Cervigon, R. 54 Cesarelli, M. 369, 426, 777, 789, 990, 1096 Cestnik, Bojan 708 Cha, H. 274 Chiap, A. 445 Chiappalone, M. 525 Cho, S.W. 1030, 1034 Choi, Y.K. 1034 Christodoulou, C. 118 Christofides, S. 313, 899 Cifrek, M. 529 Cigale, B. 1013, 1017 Cikajlo, I. 936 Cimerman, M. 327, 915 Ciprian, S. 954 Citron, P. 1140 Ciupa, R.V. 665, 895 Coer, A. 465, 589 Collins, C.G. 628 Constantinou, C.E. 286

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Conti, S. 194 Corbi, G. 78 Corino, V.D.A. 82 Coronel, R. 42 Corovic, S. 323 Corvi, Andrea 296 Couderc, B. 630 Cret, L. 665 Cugelj, R. 958 Cukjati, David 606 Cunha, D.F. 319 Cunningham, V.J. 457 Curone, D. 986 Cusella De Angelis, M.G. 238 Cvetkov, A. 1 Cvikl, M. 66

D D’Addio, G. 78 Daniel, M. 246, 282, 915 Dapena, M. A. 1038 Darowski, M. 413, 416, 871 David, Y. 1051 De Berardinis, T . 426 Debevec, H. 915 Del Guerra, A. 313 Delp, Scott 685 Dessel, P.F.H.M. van 42 Dewey, C.F. 1137 Di Giacomo, P. 1062 Di Salle, F. 509 Díaz-Zuccarini, V. 895 Diciotti, S. 847 Dickey, D. 1051 Dinevski, D. 719, 723 Docampo, M. 558 Dohi, T. 1132 Dolenc, L. 864 Dolenc, Primoz 357 Dolinar, D. 282 Dori, F. 752, 1102 Dosen, Strahinja 661 Dössel, O. 541 Dragin, A. 482 Drnovsek, J. 338, 342 Drobnič, M. 249, 253

E Efstathopoulos, E. 899 Eljon, M. 332

Index Authors

Emborg, J. 669 Ergovic, V. 677 Eroshenko, V. 911 Escoffre, J.M. 624 Eudaldo, T. 313 Evangelisti, A. 847, 932

F Fajdiga, I. 864 Farina, D. 109, 541 Fassina, L. 238 Fatemi, M. 1021 Faustini, G. 723, 727 Fazekas, G. 266 Feng, J. 278 Fernandes, H. 505 Ferrara, N. 78 Ferrario, M. 781 Fidler Mis, Natasa 166 Filligoi, Gian Carlo 124 Fink, M. 50 Fischer, R. 22 Forjaz Secca, M. 505 Fortunato, P. 847 Frank, M. 566 Fratini, A. 369, 426, 789, 990, 1096 French, P.M.W. 1134 Fridolin, I. 350 Frigo, C.A. 292 Fritzson, P. 685 Fujii, T. 170 Furuse, Norio 689

G Gados, D. 802 Gajsek, P. 218, 222, 234 Gamberger, D. 157 Garfield, R. E. 128 Gargiulo, G. 369 Gazzoni, M. 109 Gerogiannis, I. 879, 899 Gersak, G. 342 Ghandour, H. 170 Giacomini, M. 693 Giansanti, D. 745, 749, 1006 Gieras, I. 1051 Gilly, H. 1070 Giovagnoli, M.R. 745, 749

Glapinski, J. 413 Glaser, V. 105 Goldmann, T. 300, 304 Goljar, N. 936 Golzio, M. 610, 624, 630 Gopalsami, N. 346, 911 Gorisek-Humar, M. 681 Goszczynska, Hanna 793 Gouliamos, A. 899 Grabec, D. 867 Grabljevec, K. 393 Grasser, S. 1058 Greenleaf, J.F. 1021 Grmec, Š. 716 Grobelnik, B. 859 Grosel, A. 582, 589 Gryaznova, V.A. 257 Gudmundsson, V. 139 Guelaz, R. 377 Güler, G. 230, 214

H Hafner, C. 1058 Halasz, G. 430 Hamar, G. 818 Hamid, Azman 1089 Han, K.W. 839, 1030, 1034 Hana, K. 86 Hart, F.X. 190 Hasan, Muhammad Kamrul 405 Hatakeyama, Y. 286 Heblakova, E. 86 Heida, T. 521 Heyman, J. 1051 Hidalgo, M. A. 1038 Himmlova, L. 300 Hinrikus, H. 210 Hocevar, F. 958 Hofer, C. 658 Hofstra, W.A. 487 Holcik, J. 62 Holder, D.S. 798 Holobar, A. 105, 109, 114 Hong, J. 274 Horvath, G. 802, 818 Hose, D.R. 895 Hudej, R. 875, 883 Husser, D 82 Hyman, W. 1051 Hyndman, B. 1051

Index Authors

I Iadanza, E. 752, 1102 Ide, A.N. 525 Iglic, A. 246, 282, 903 Ihan Hren, N. 943 Ilias, Michail 1122 Inchingolo, P. 509, 513, 719, 723, 727, 732, 1107 Inchingolo, P. 1077 Infantosi, A.F.C. 492, 1025 Innocenti, Bernardo 296 Isgum, V. 529 Istenic, R. 114 Ivanova, T. 923 Ivanovski, M. 282 Izzetoglu, M. 473

J Jafari, Ayyoub 99 Jager, F. 34 Jagomägi, K. 562 Jan, J. 174 Jancar, J. 234 Japundzic-Zigon, N. 773 Jarm, T. 148, 469, 1002, 1009 Javorka, K. 766, 769 Javorka, M. 766, 769 Javorkova, J. 766, 769 Jelovsek, A. 704 Jenko, M. 737 Jerotskaja, J. 350 Jobbagy, A. 266 Johnson, J.H. 190 Jovic, Alan 549 Jovic, S. 482 Jung, Y.C. 1034

K Kaik, J. 554 Kalaitzis, A. 879 Kamarianakis, Z. 826 Kamnik, R. 288, 950, 954 Kantelhardt, J.W. 38 Kaplanis, P. 118 Kaplanis, P.A. 879, 899 Kapus, J. 994 Kapus, V. 994, 1002 Karas, S. 86 Karba, R. 478, 501

1145

Kardamakis, D. 923 Karlsson, B. 135, 139 Kasovic, M. 677 Kasthuri, U. 856 Katrasnik, J. 947 Kawahara, K. 537 Keil, O. 1051 Keller, J. 1051 Kern, H. 658 Kervina, D. 737 Khang, G. 274, 835 Khir, A.W. 278 Kim, D.Y. 1030 Kim, I.Y. 839, 1030, 1034 Kim, J.J. 839, 1034 Kim, S.I. 839, 1030, 1034 Kim, Y. 274 Kinsella, R. 1055 Kitney, R.I. 814, 1138 Klemen, A. 681 Knaduser, Masa 570 Kneppo, P. 86 Kochemasov, G. 856, 911 Koder, J. 253 Kohn, A.F. 419 Kokol, P. 716, 719 Konno, D. 442 Konvickova, S. 300 Koren, A. 864 Koritnik, B. 478, 501 Koritnik, T. 262 Kos, A. 323 Kostka, P.S. 70 Kotnik, S. 965 Kotnik, T. 639 Kourtiche, D. 377 Kozarski, M. 416 Kozelek, P. 62 Kozelj, A. 716 Krajnc, I. 719 Krajnik, J. 681 Kralj, P. 157 Kralj-Iglic, V. 246, 282, 566, 903, 915 Kramar, P. 574, 578 Kranjc, M. 574 Kranjc, S. 469, 582, 589, 602 Krbot, M. 529 Krcevski-Skvarc, N. 716 Krečič-Stres, H. 253 Kregar-Velikonja, N. 249, 253 Krevs, Luka 381

Kristan, A. 915 Kristl, J. 453 Krizaj, D. 174, 178, 182, 393 Krizmaric, M. 716 Krkovič, M. 253 Krstacic, A. 157 Krstacic, Goran 549 Krzan, M. 566 Ku, J.H. 839, 1030, 1034 Kulikov, S. 346 Kuraszkiewicz, B. 871 Kurillo, G. 478 Kybartaite, A. 329

L La Gatta, A. 990 La Torre, A. 847 Lackovic, I. 631 Laguna, P. 74 Landa, M. 304 Lanmüller, H. 651 Lass, J. 210, 434 Lauri, K. 350 Lavrac, N. 157, 708 Lawford, P.V. 895 Lazarevic, I. 741 Leal, A. 505 Lebar, A. Macek 578 Lee, H.R. 839 Lee, S. 274 Lee, W.H. 242, 839 Legan, M. 465 Legrand, D. 170 Lendyak, A.A. 700 Lenic, M. 1013 Lennon, E. 170 Leskosek, B. 131 Levin, O. 643 Lewis, C. A. 1 Lindroos, K. 329, 336, 1111 Lindroos, K.V. 1130 Linehan, J.H. 1142 Linnenbank, A.C. 42 Lipschultz, A. 1051 List, I. 282 Livint, Gh. 954 Ljesevic, B. 482 Lo Sapio, M. 969 Loffredo, L. 426 Logar, V. 478, 501 Lokar, M. 566

1146

Loncar-Turukalo, T. 773 Londero, F. 1107 Lorandi, F. 693 Lorens, A. 940 Lu, S.K. 242 Lucache, D. 954 Lukosevicius, A. 1126 Luman, M. 350 Lunghi, F. 781, 986 Lyubynskaya, T. 438, 911

M Maccioni, G. 1006 Macek-Lebar, A. 144, 148, 178, 332 Macellari, V. 1006 Macrini, J.L.R. 1025 Magenes, G. 238, 781, 986 Magjarevic, R. 46, 58, 397, 631 Magli, A. 426 Mahady, J. 1055 Mahmudi, Hedyeh 696 Mainardi, LT 82 Malatara, G. 923 Malataras, P.G. 1092 Maličev, E. 253 Malik, M. 74 Malmivuo, J. 329, 1111 Malmivuo, J.A. 336, 1115 Maner, W. L. 128 Manis, G. 785 Marani, E. 521 Mareš, T. 246 Margo, C. 186 Marini, E. 752 Marjanovic, T. 206 Marolt, D. 253 Marozas, V. 1126 Marque, C. 135, 139 Martinoia, S. 525 Martorelli, M. 969 Martynov, A. 346 Marwala, T. 806 Masamune, K. 1132 Maslov, N.V. 856 Masuko, T. 647 Mateo, J. 54, 90 Matjacic, Z. 673, 681, 936 Matko, D. 501 Matsumiya, K. 1132 Matsuoka, T. 442 Mattei, S. 1102

Index Authors

Mavcic, B. 282, 915 Maver, T. 943 Mayr, W. 658 Mazurier, J. 170 Mazzolini, L. 624 McEwan, A.L. 798 Medved, V. 677 Meesen, R.L.J. 643 Meigas, K. 434, 554 Melillo, P. 758 Melinscak, M. 198 Melnyk, O.O. 257 Mendez, M.O. 30 Mendonca, F.B. 319 Meneghini, F. 509, 513 Merletti, R. 109, 114 Merzagora, A. C. 473 Mesojednik, S. 589 Micetic-Turk, D. 716 Michnikowski, M. 413 Micieli, Giuseppe 152 Mihel, J. 58 Mikac, U. 859 Miklavčič, D. 178, 218, 226, 323, 332, 381, 570, 574, 578, 593, 597, 602, 606, 631, 635, 639, 851 Milicic, P. 1100 Millet, J. 54 Milutinovic, S. 773 Mininel, S. 509, 513, 723 Miodownik, S. 1051 Mir, L.M. 606, 622, 623 Miri, R. 541 Mödlin, M. 658 Molan, G. 162 Molan, M. 162 Molnar, F. T. 430 Moon, H.J. 835 Morradi, M.H. 99 Morrissey, A. 628 Morse, W. 1051 Munih, M. 262, 288, 950, 965, 973, 982 Murayama, Y. 286 Mutapcic, A. 423

N Nadi, M. 186, 377 Nagel, J.H. 1043, 1118 Nagel, M. 1043

Nakayama, Y. 537 Nalivaiko, E. 26 Nam Koong, K. 1034 Narracott, A.J. 895 Nascimento, L.N. 1085 Nekhoul, B. 843 Neumann, Eberhard 18 Ng, S.C. 517 Niknam, Kaiser 696 Niknam, Sahar 696 Nikolopoulos, S. 785 Noaman, Noaman M. 385 Norgia, M. 390 Nousiainen, J. 329, 1111 Nousiainen, J.O. 336, 1115 Novak, D. 148 Nuzhny, A. 438

O O’Sullivan, G.C. 628 Oblak, J. 178 Obreza, P. 950 Obrycka, A. 940 Ogawa, M. 442 Olensek, A. 673, 681 Olsen, K. J. 313 Omata, S. 286 Omejec, G. 998 Onaral, B. 473 Oostendorp, T.F. 42 Oosterom, A. van 42 Osorio, I. 346, 911 Osswald, B. 541 Ott, J. 1051 Ottaviano, M. 558 Ozgur, E. 214

P Pacini, G. 194 Padovani, R. 313 Paganin-Gioanni, A. 624 Paglialonga, A. 390 Painter, F.R. 1085 Palko, K.J. 416 Palko, T. 940 Pallikarakis, N. 826, 923, 928 Pallikarakis, N.E. 373, 1092 Panzarasa, Silvia 152 Papic, M. 323 Parazzini, M. 390

Index Authors

Park, J.S. 839, 1030, 1034 Park, K.S. 835 Park, Y. 274 Pasquariello, G. 426, 990, 1096 Patail, B. 1051 Pattichis, C.S. 118 Pauly, J.M. 423 Pavan, E.E. 292 Paver-Erzen, Vesna 327 Pavlic, J. 903 Pavliha, Denis 381 Pavlin, D. 589 Pavlin, M. 593, 635 Pavlovic, I. 741 Pavlycheva, I.Yu. 856 Pavselj, N. 597 Pecchia, L. 758, 762, 1066 Pedreira, C.E. 1025 Peer, P. 947 Peinado, I. 558 Pentony, P.J.C. 1055 Perdan, J. 950 Pereira, W.C.A. 1025 Pérez, J. F. 1038 Pesatori, A. 390 Pessina, Mauro 152 Petersson, G. 685 Petric, P. 875 Piggott, J. 628 Pilt, K. 434 Plesa, M. 665 Poboroniuc, M.S. 954 Podobnik, J. 973 Podsiadly-Marczykowska, T. 871 Poh, C.-L. 814 Poli, A. 723, 732 Pone, A. 1066 Poola, G. 202 Popovic, B. 661 Popovic, D.Lj. 310 Popovic, D.B. 3, 654 Popovic, Mirjana B. 3 Prado, J. 186 Prado, Manuel 712 Praprotnik, L. 365 Praznikar, A. 681 Prcela, Marin 549 Preat, V. 597 Pucihar, G. 639 Pueyo, E. 74 Pur, Aleksander 708 Pusnik, I. 338, 401

1147

Pustisek, M. 737 Putten, M.J.A.M. van 487, 497, 756

Q Quaglini, Silvana 152

R Raamat, R. 562 Radosavljevic, D. 249 Rafiroiu, D. 895 Rajalakso, M. 1130 Rajsman, G. 46 Rakos, M. 658 Ramat, S. 977, 986 Ramos, P. 1038 Raptis, A.C. 346 Ravazzani, P. 390 Raveendran, P. 517 Rawicz, M. 413 Rebersek, M. 381, 574 Rener, K. 354 Rengo, F. 78 Reumann, M. 541 Reyes-Aldasoro, C.C. 810 Rhee, K. 835 Riener, Robert 7 Rieta, J.J. 90, 94 Roa, Laura M. 712 Rodriguez, B. 50 Rols, M.P. 610, 624, 630 Romano, M. 369, 426, 777, 789, 990, 1096 Rose, J. 685 Rosik, V. 86 Rosmann, M. 434 Rossum, A.C. van 42 Rouane, A 186 Rozman, B. 246, 566 Rubenchik, A. 856 Rubin, D.M. 806 Rubinsky, Boris 629 Rudel, D. 131, 144, 148 Rudolf, M. 936 Ruggiero, C. 693 Rutar, V. 478, 501

S Sadadcharam, M. 628 Saino, E. 238

Sakhaeimanesh, A.A. 545 Sakuma, H. 286 Salerud, E.G. 1122 Salobir, B. 354 Salvi, D. 558 Samini, Mahdi Ghorbani 696 Sanchez, C. 54, 90 Sanders, P.M.H. 756 Sandholm, A. 685 Sanguineti, V. 525 Sarabon, N. 998 Sarker, Md. Atiqur Rahman 405 Sarvari, A. 887 Sayadat, Md. Nazmus 405 Sbrignadello, S. 194 Scabar, A. 445 Scherbakov, A. 350 Schlegel, W. 313 Schmidt, G. 38 Schneider, R. 38 Schwirtlich, L. 482, 654 Secerov, A. 469 Sefer, A.B. 529 Seiner, H. 304 Senez, V. 170 Sentjurc, M. 453, 570 Sersa, G. 465, 469, 582, 589, 602, 614 Sersa, I. 859 Seyhan, N. 214, 230 Shakhova, N.M. 856 Sharp, P. F. 313 Shepherd, M. 1051 Shrestha, R.B.K. 814 Shumsky, S. 438 Sibella, F. 390 Signorini, M.G. 781 Silva, L.B. Da 856 Simunic, B. 393 Skannavis, S. 879 Skarzynski, H. 940 Sladoievich, E. 752 Smrcka, P. 86 Smrdel, A. 34 Soden, D.M. 628 Soimu, D. 826, 928 Sovilj, S. 46 Spaich, E. 669 Spasic-Jokic, V.M. 310 Spyrou, S.P. 879 Stankiewicz, B. 413 Stankovic, S. 310

1148

Stankovski, Vlado 166 Stare, Z. 206 Starfield, D.M. 806 Stefanovic, A. 482 Stefanoyiannis, A.P. 879, 899 Steingrimsdottir, T. 135, 139 Stern, M. 704 Stet, D. 665 Stiblar-Martincic, D. 465 Stikov, N. 423 Stimec, Matevz 166 Stirn, I. 1002, 1009 Stoeva, M. 1 Strojan, P. 867 Strojnik, A. 891 Strojnik, V. 1002, 1009 Strumbelj, B. 994 Stublar, J. 288 Surace, A. 752 Svelto, C. 390 Swain, Martin 166 Swinnen, S.P. 643

T Tabakov, S 1 Takenoshita, S. 286 Talts, J. 562 Tamzali, Y. 610, 630 Tan, H.L. 42 Tanougast, C. 843 Taran, E.Yu. 257 Tarassenko, L.T. 50 Tarjan, Zs. 818 Teissié, J. 610, 618, 624, 630 Terio, H. 1047, 1074 Terrien, J. 135, 139 Tevz, G. 589 Thierry, J. 1058 Tian, T.Y. 242 Tkacz, E.J. 70 Tobey Clark, J. 1051 Tognola, G. 390 Tomruk, A. 230

Index Authors

Tomsic, I. 681 Tomsic, M. 282, 961 Tomson, R. 210 Tonhajzerova, I. 766, 769 Tonin, M. 915 Tonkovic, S. 677 Toomessoo, J. 202 Torkar, Drago 851 Toscano, R. 932 Tozer, G.M. 457, 810 Tozon, Natasa 586 Tranfaglia, R. 1066 Tratar, G. 859 Trcek, T. 222 Treizebré, A. 170 Trunkvalterova, Z. 766, 769 Tura, A. 194 Turk, Z. 716 Tuulik, V. 210 Tysler, M. 86

Villantieri, O.P. 30 Virag, T. 818 Visai, L. 238 Vizintin, T. 1002 Vrhovec, J. 144, 332

W Walkowiak, A. 940 Wasowski, A. 940 Watanabe, T. 647, 689 Wear, James O. 1081 Weingartner, J. 943 Wernisch, J. 651 Wheeler, B.C. 477 Woloszczuk-Gebicka, B. 413 Wong, J. 830

X Xyda, M.G. 118

U Urbanija, J. 246, 566 Usaj, A. 461, 994 Usaj, Marko 851 Usenik, P. 288 Usunoff, K.G. 521

V Valchinov, E.S. 373 Valic, B. 218, 222, 226, 234 Väliharju, T. 1130 Varga, D. 773 Vatta, F. 509, 513, 723, 1077, 1107 Vaya, C. 90 Veber, M. 947, 982 Verdenik, I. 131 Vidmar, G. 131 Vidmar, J. 859 Vilimek, M. 308 Villalba, E. 558

Y Yajima, T. 286 Yeh, H.I. 242 Yoshizawa, M. 647

Z Zaeyen, E.J.B. 492 Zagar, T. 174, 182 Zazula, D. 105, 109, 114, 118, 1013, 1017 Zemva, A. 66, 357 Zidar, J. 478, 501 Zielinski, K. 416 Zoia, S. 445 Zrimec, T. 822, 830 Zupan, A. 681, 958 Zupanic, A. 226 Zupunski, I. Z. 310 Zuzek, A. 943 Zywietz, T.K. 22

Index Subjects 2 2D/3D 834

3 3-axes accelerometer 369 3D Motion Analysis 300 3D reconstruction 826 3D ultrasound images 1017 3-dimensional scaffold 249

A a model of lung and airway 871 absorbance 350 Accessible Web Design 737 accuracy 338, 361 acetabular fracture 915 Acetylcholine 521 action potential duration 42 activation time imaging 42 active medical implanted devices 390 adaptive filtering 135, 990 Adaptive stuttering therapy 712 Afferent stimulation 643 Aggregated autocorrelogram 442 Agreement detector 442 AH-graph 162 AH-model 162 AH-semantic 162 airway segments 871 alcohol craving 1034 ambient assisted living 397, 723 ambulatory blood pressure monitoring 357 amiodarone 82 amplifier 373 analog 879 anisotropy 509 Antennessa DSP 090 222 Anthropomorphic robotics 986 antioxidant 214 Antiphospholipid antibodies 566 antitumor treatment 622 Apolipoprotein 246 applanation tonometry 354 approximate entropy 144

approximate entropy algorithm 785 approximation methods 677 Arm Therapy 7 ARMAX 385 arrhythmic death 74 arterial catheter 430 artificial neural networks 438, 501 Artificial Neural Networks (ANN) 478 Artificial vision 977 assessment 1070 Assistive Technology 737 atherosclerosis 835 Atrial Activity 94 atrial fibrillation 82 Atrial Fibrillation 54, 94 atrio-ventricular block 541 attention 473 attenuation measurements 923 Austria 1070 Automated cell counting 851 automatic clinical tracing 1062 autonomic nervous system 38, 82 Autonomic nervous system 932 Avascular necrosis 282 avatar 1034 a-wave 919

B balance 998 baroreceptor reflex 773 Baseline 90 battery powered 798 BEMS 1089 bending stiffness 270 Berg balance scale 936 Beta-2-glycoprotein I 566 Beta-2-glycoprotein-I 246 between-step control 673 biceps brachii muscle 109 binocular 977 bioelectric phenomena 631 Biofeedback 961 bioimpedance 182, 202 bioimpedance spectroscopy 186 biomechanics 915 Biomechanics 282

Biomedea 1043 biomedical engineering 1089, 1115 Biomedical engineering 1122, 1126 Biomedical Engineering 329, 1111 biomedical engineering advancement 1140 Biomedical Engineering Technicians 1081 Biomedical informatics 319 biomedical instrumentation 369 biomedical technology management 1092 Biomems 170 biomimetic artifacts 986 biomimetics 238 biopotential electrode 373 biosignal measurement 86 Bishop Score 131 biventricular pacing 541 bleomycin 602, 614, 622 blood 186 blood clots 859 blood flow rate 457 Blood pressure 434 blood pressure measurement 342 blood pressure variability 357, 773 blood pulsation 839 Blood Velocity 810 blood volume 461 blood-transfusion 1062 Bluetooth 369, 798 BME 1077 BME accreditation 1118 BME education 1107, 1118 BMET 1081 BMSC 253 body area network 397 body surface mapping 42 BOLD 505 Bologna 1122 Bolus Processing 300 bone healing 253 bone marrow 253 botulinum toxin 393 brain 461 brain activity mapping 513 brain ischaemia 157 brain lesion 509

1150

brain microcooler 911 Brain symmetry index 487 brain trauma 482 breast 1025 breast cancer 438, 856 Breathing retraining 961 BSI 487

C CAD-system 802 CAHTMA 1081 calcium oscillation 537 calculation algorithms 562 calibration bath 338 Cancellation Noise 90 Cancellous Bone Tissue 274 cancer 629 Cancer 628 cancer therapy 457 cardiotocography 777 Carotid endarterectomy 487 Cartilage Wear 814 catechin 230 cats 586 Cavitation 895 CE certification 1118 CE continuing education 1118 cell clusters 639 cell electroporation 593 cell membrane fluidity 570 Cell Signaling 170 center of pressure 936 Central ECG analysis and interpretation 22 Certification 1081 cervical spine 270 cervix 131 charge density 903 Chest 802 chest electrode 554 children 445 choice reaction time 529 chondrocyte 249 Chronic Heart Faillure 758 cisplatin 582, 586, 602, 610, 614, 622 citizen-centric health-care 723, 727 classification 66, 822 Classification 843 clinical data 741 clinical engineering 310, 1043, 1089, 1107

Index Subjects

Clinical engineering 1074 Clinical Engineering 1051, 1055, 1070, 1077, 1085, 1096 Clinical engineering activities 1085 clinical engineering profile 1085 Clinical Engineers 1081 Clinical Practice Guideline 152 clinical thermometer 338, 361, 401 clinical training 327 clinical trial 741 clinical trial solution 22 Cliniporator 10 closed-loop FES 950 closed-loop system 911 CMRR 798 cochlear implant 332, 940 cochlear implants 390 Coded apertures 806 coil design 665 Collaboration 329 combretastatin 457 Communication Protocol 405 complexity 26 Compound signal decomposition 105 Computer Aided Diagnosis 830 computer aided surgery 1132 Computer Simulation 50 computer vision 947 Congenital nystagmus 426 Congestive heart failure 541 conical collimators 887 Continuous EEG 756 Continuous monitoring 58 continuous wavelet transform 1017 contractility 296 contractions 148 contrast set mining 157 control 478 convolution kernel compensation 109, 114 COPD 961 COPD patients 78 coronary flow rate measurements 793 Cortical Bone 304 cortical network 525 cost 756 cross-correlation 525 cross-interval histogram 109 CT 864 culture 477 cultured cardiac myocytes 537

cutaneous tumours 614 cycle-to-cycle control 647

D data mining 166, 677 Data presentation methods 708 data visualization techniques 708 database 166 databases 1137 DC component 434 Decision Aid 696 Decision Analysis 696 decision support 14, 762 Decomposition 118 Deep Brain Stimulation 651 delay of cardiac repolarization 22 delivery 618 denervated degenerated muscles 658 dense system 635 desmin 242 detection 66 Device failure 651 Dexterity Assessment 982 diabetes 194 Diabetes Management 14 diabetes mellitus 766, 769 diagnosis 128 diagnostic imaging 292 diagnostics 818 dialysis dose 350 dialysis monitoring 350 dialysis quality 350 Dielectric & Vibrationnal Spectroscopy 170 dielectric properties 186 dielectrophoresis 178 digital 879 digital mammography 899 digital pathology 745, 749 Digitising 943 Diodes 891 dipole rearrangements 18 Disability 737 discretization 246 Disease Pattern Recognition 830 disorder classification 677 dissipation 278 Distance education 319 distributed 166 distributed health care 723, 732 diversity 1142

Index Subjects

DNA electrotransfer 18, 606 DNA injections 623 Doctor.UA 700 dogs 586 dose distribution 923 dose verification 883 dosimetry 218, 887 Dosimetry 222, 226, 234 drop-foot 654 drug delivery systems 602 DSP based measuring system 86 Dysautonomic neuropathy 932 dysgraphia 445 Dysport 393

E ear 332 ECG 66, 94, 369, 373 ECG acquisition 58 ECG analyzer 405 EDC 741 Edge detection 818 education 716 Education 313, 737 Education and Training 1 EEG 487, 501, 505, 509, 513 EEG analysis 210 effective conductivity 635 effective medium 635 EGCG 214, 230 e-health 745, 749 EHG 135, 139 EITS 798 elastic model 246 Elasticity 286 e-learning 323, 336, 749, 1107, 1115 eLearning 329 e-Learning 1 E-learning 319 E-learning material 1111 electric field distribution 323 Electrical Cardioversion 54 electrical model 182 electrical stimulation 521 Electrical stimulation 3 Electrocardiogram 74 electrochemotherapy 323, 582, 610, 614, 618, 631 Electrochemotherapy 628 electrode configurations 390 electrode displacement sensitivity 206

1151

electrode tissue interface 198 electrodes 477 Electroencephalography (EEG) 478 electrogenotherapy 618 electrolytes in endodontic 206 Electromagnetic fields 222, 234 electromagnetic interferences 1066 Electromagnetic stimulation 238 electromyogram 148 electromyography 128, 1002 electronic apex locator 206 electronic data capturing 22 electronic data collection 741 Electronic Patient Record 152 electropermeabilization 323, 597, 606, 618 Electropermeabilization 622 electroporation 178, 570, 586, 589, 597, 602, 606, 614, 618, 622, 631, 639, 851 Electroporation 624, 628 electrorelease 18 electrotransfer 582 ELF-E Field 230 Embedded System 381 emergency medical system 704 Emergency Patient Care Report Form 1058 Emergency Systems 1058 EMF effect 210 EMG 118, 128, 131, 1009 EMG force relation 114 Employment 737 Encoding 152 endocytosis 623 Endoscope 628 endotracheal tube 413 endurance level 1009 entrepreneurship 1142 epilepsy 346, 482, 911 Epilepsy 505 Epitheses 943 EPR in vivo 453 equalization 899 Equipment Alarm Systems 1051 equipment inventory 1092 ERG 919 estimation 839 estimator 385 Ethernet connectivity 86 evaluation 899 EVICAB 1111

excitation 1134 exercise testing 82 Experiment in Vivo 300 experimental tumors 469 expert system 549 Exploratory data analysis 157 extracellular matrix 238 extracellular matrix components 589 eye movement 426

F fatigue 288, 1002 feature extraction 70 feature selection 70 Femoral head 282 FES 658, 689 fetal cardiac arrhythmias 789 Fetal monitoring 781 film dosimetry 883 Finapres 562 finger pulse pressure 562 finger-tapping 266 finite element analysis 270 Finite element method 226 finite elements 218, 597 finite-element method 631 fixed-point 361 flecainide 82 flow 859 flow resistance 413 flow-volume curves 871 fluid structure interaction 895 fluorescence 1134 fMRI 505, 839 fNIRS 473 Force tracking task 950 foveation 426 FPGA 66 FPGA, Ethernet 202 fractal analysis 78 free radical 214 FreeForm 969 frequency response 430 function assessment 1096 functional connectivity 525 Functional electrical stimulation 661 functional electrical stimulation (FES) 647 Functional electrical stimulation (FES) 654

1152

Functional electrical therapy (FET) 654 fuzzy controller 647 Fuzzy Logic 696

G Gait 685 gait phase 689 Gait Therapy 7 gait training 1030 gap junctions 537 gene electrotransfer 574, 623 gene therapy 606 Gene Therapy 628 gene transfer 597 Giant phospholipid vesicles 566 global outliers 789 glucose transporter-1 465 glycaemia 194 Graphical User Interface (GUI) 381 grid 166 grip force 973 grip strength 954 Ground reaction force 669 gyroscope 689

H half power region 665 half-beams 883 hand closing 950 hand opening 950 hand rehabilitation 954 Handwriting 445 haptic feedback 1038 haptic interface 965, 973 Haptic modeling 969 Hardware 1058 harmonization 1122 Head model 509 Health Care Integration 719 Health Care System 708 health care technology 1070 Health Information Systems 719 health monitoring 558 health process 1102 Health System 752 Health Technology Assessment 758 health tissue protection 928 Healthcare system 1100

Index Subjects

healthcare systems 1077 Heart rate analysis 781 heart rate variability 26, 773, 785 Heart rate variability 38, 766, 769 Heart valves 545 hemiplegia 654 hemiplegic gait disorder 1030 hemodialysis 350 Hepatitis 286 HERG 50 Hierarchical hybrid control 3 hierarchical SOM 977 high speed power MOSFET driver 574 higher education 1077 Hill-type model 308 hip contact stress 915 Hip stress 282 HL7 693, 704 Honeycombing 830 horses 586, 610 hospital engineering 1070 hospital support services 1089 HPC 513 HRCT 822 HRV 78 HTA 762, 1100 human factors 162 Human Femoral Head 274 human gait 677 human hand 365 Human hand 982 Human locomotion 669 human patient simulator 716 human smooth muscle cells 242 hydroporation 623 hypoxic marker 465

I ICT 1077, 1130 identification 385 IHE 732 Image Guided Therapy 834 Image Modulated Radiation Therapy 834 Image Registration 834 Image segmentation 847 images registration 793 imaging 624, 798, 879, 1134 Imaging 1021 imaging monitored 629

immunohistochemistry 465 impedance 190 impedance method 174 impedance spectroscopy 174 Impedance spectroscopy 194 impedance transformation 416 impedance-ratio measuring method 206 implant 911 Implantable 346 implants 218 IMRT techniques 867 in vitro 570 In vivo dosimetry 891 incremental bicycle exercise 994 index 1102 Induced electric current 226 information and communication technologies 14 information exchange 704 information graphics 708 information system 704 innovation 1142 inotropism 296 instrumentation 798 instrumented gait analysis 681 Integrate-and-Fire unit 442 intellectual property 10 intelligent matrix electrode 654 Intensive care unit (ICU) 58 Interactive Notebook 685 intercellular synchronization 537 international cooperation communities 723 internationalization 727, 732 Internet 319, 336 internet site 332 Internet-systems 700 interoperability 727 Interoperability 719 intravital microscopy 457 Inverse Problem 304 inverse procedure 42 ion diffusion 593 IRIS Home 958 irregular volume shielding 928 irreversible electroporation 629 isometric conditions 950 isovolume-pressure-flow curves (IVPF) 871 ITCN algorithm 851 IT-systems 1047

Index Subjects

K kinematic analysis 445 kinematics 288 Kinematics 300 kinetics 288 knee control 1030 knee joint 647 KNN 843 knowledge acquisition 549 KPI 752

L labor 128, 131, 135, 139 labour intensity 756 LDA technique 545 learning 1126 Learning management system 1130 left bundle branch block 541 left ventricle 895 leg 461 linear accelerator 887 linear rising signal 578 liver 230, 629 Liver cirrosis 286 Living Cell 170 Local arterial compliance 562 local outliers 789 localization 665 lock-in technique 182 long bone defects 253 low frequency exposure 218 lower extremities 658 lower extremities training 262 luciferase 589 lumped parameter model 895 Lung 802 Lung HRCT 830 lung surface 822 lungs mechanics 416 lungs model 416

M machine learning 822 magnesium alloys 242 magnetic additions 257 magnetic stimulation 665 maintenance 1096 Management 752 mapping 139

1153

marketing 10 Markov model 50 markup languages 1137 Mastication 300 Matrix of Elastic Coefficients 304 mean frequency 1002 measurement system 182 mechanical heart valve 895 mechanical ventilation 413 median filter 789 medical and pharmaceutical information 700 Medical Decision Making 696 Medical Device Safety 1051 Medical devices 1047 Medical Diagnosis 696 medical image processing 818 medical informatics 741 medical information systems 1047 medical physics 310 Medical Physics 313 medical plans 549 medical reporting workstation 727 medicine 166 meduloblastoma 867 membrane permittivity 178 membrane surface 903 MEMS sensors 661 mesenchymal stem cells 253 method of impedance 430 methodological tool 1102 Mexican-Hat 919 mice 469 Micro Tactile Sensor 286 Microcontroller 405 microelectrode arrays 525 microelectrodes 186 microfluidic study 257 Microprocessor 381 Microscopic Multi-Directional Property Measurement 274 MIDS 1047 minimally invasive surgery 629 Missing fundamental 442 MLAEP 492 MNF 1009 Mobile and Wearable Devices 1058 mobile phone 214 model semantic 162 Model-based control 3 modeling 631 Modeling 118, 685

Modelling 377 molecular imaging 835, 1135 monitoring 194 Monitoring 234, 1051 monopolar recording 135 Monte Carlo 928 Monte Carlo simulation 923 Monte-Carlo Simulation 304 Moodle 1107, 1130 morphometric parameters 1025 motor development 365 motor unit synchronization 109 movement analysis 266 movement planning 986 movement related evoked potentials 529 moving object tracking 793 MR microscopy 859 MRI 423 MUAPs 118 multimodal imaging 509 Multimodal monitoring 712 multiple electrodes 574 Multitier architecture 712 muscle 288 muscle fatigue 517, 1009 muscle force estimation 114 Muscle mechanics 308 Muscle oxigenation 124 musculoskeletal model 661 musculoskeletal modeling 292 Mutual information 1025 MVCBCT 928 myocyte 296 Myoelectric signal 124

N Nano particles 903 Nano-Electrode and wire 170 nanomedicine 1135 nanoparticle 835 nanotechnology 1135 Natural Language Generation 152 Near Infrared Spectroscopy 124 neonatal incubator 1096 networks 477 Neural 477 neural network 1025 Neural networks 847 Neural Networks and Madeline 90 neural noise 419

1154

neurology 497 neuromuscular disorders 681 neuroplasticity 643 newt 190 NIBP 342, 385 NIRS 461 NIRS Slow-Fast phase 124 Nociceptive withdrawal reflex 669 noise 798 non invasive inspection 651 non-invasive 194 noninvasive ischemia identification 86 non-invasive measurement 434 nonlinear 377 nonlinear dynamics 769 nonlinear dynamics, complexity 766 nonlinear lungs models 416 Non-linear methods 781 nonthermal effect 210 Non-Viral Gene Therapy 623 Nuclear medicine imaging 806 Numeric model 296 numerical methods 635 numerical model 639 numerical modeling 218, 323, 597

O objective methods 940 Objective Response Detection 492 obstructive sleep apnea 864 Obstructive Sleep Apnea 30 odontoid fracture 270 ody surface potential mapping 86 office blood pressure 357 Online Education 329 Open Access 329 Open Source 719 Open Standards 719 open-source 723, 727, 732 Optical Coherence Tomography 847 optical scattering spectrum 438 optimal tracking 661 optimization 851 order parameter 570 Organization 94 orthopaedic surgery 292 orthostatic test 461 oscillation 545 oscillometry 342

Index Subjects

Osteoarthritis 814 osteoblast 238 outcome measurement 965 outer volume suppression 423 ovarian follicles 1017 oximetry 453

P p53 582 Pacemaker 1066 PACS 732 PAM 266 Partial volume effect 806 Patient Care Management 1051 patient groups 756 Patient safety 1043 Patient Safety 1055 Patient-Cooperative 7 patients 1140 pattern classification 473 pattern recognition 70 peak alpha frequency 517 pedometers 1006 PEMS 1047 Performance Indicators 752 Performance Measures 752 Personal Area Network 405 Personal Computer (PC) 381 Personal monitoring device 369 personalized applications 558 Personalized healthcare 397 personalized medicine 693 persons with disabilities 958 Pharmacogenomics 693 phase contrast images 851 phase demodulation 478 phase-rectified signal averaging 38 phenotype 249 photoplethysmography 434 physical hybrid lungs models 416 Physiological 1051 Physiome project 1137 pimonidazole 465 planar lipid bilayer 578 polar fluid 257 polarisation effect 186 Policy Statement 313 pore stabilization 593 postural control model 419 postural oscillations 419 postural response 936

potential distribution 390 power absorption within-step control 673 Power density spectra 545 power grip 365 PPG 839 precision grip 365, 973 prediction 128 Pregnancy 226 pre-operative planning 292 principal component analysis 70 privatization 1089 programs 1126 propagation 139, 377 Prostate Cancer Diagnosis 843 Prostheses 943 prosthesis 965 protein carbonyl level (PCO) 230 Psycho-acoustic Threshold 492 Pulmonary rehabilitation 961 Pulse wave 354 pulse wave transit time 434 purinoceptors 537 push-off 673

Q qEEG 482 QFD 1102 QT/QTc-study 22 QT/RR 74 quadratic phase 423 quality 1062 quality measurement 1102 quantitative EEG 497, 756

R Radiation force 1021 Radio Frequency 214 Radiographs 802 radiology 879 radiotherapy 867 Radiotherapy 891, 928 Rapid prototyping 943 rat 26 rating stroke patients 266 ratio method 174 reaction time 529 real-time PCR 249 Real-time signal processing 105 recurrence plot 769

Index Subjects

recurrence quantification analysis 769 Red Blood Cell Tracking 810 reduced breathing frequency 994 Reflex modulation 669 regeneration 190 rehabilitation 915, 965, 1030 Rehabilitation 982 Rehabilitation Robotics 7 rehabilitation technology 958 repeatability 998, 1009 repolarization 74 Resolution enhancement 806 Respiratory muscles 961 response prediction 501 RF saturation pulses 423 RFID 1062, 1066 ripeness 131 ripple-down rules 822 RNA interference 624 root canal 174 root canal length 206 rotational radiotherapy 923 Rule-based control 3

S Safety 1066 sample entropy 144 Sample Entropy 54, 94 Sampling considerations 806 sarcoma experimental – drug therapy – blood supply 602 sarcomere 296 SAW 346 SBS 843 SD 777 segmentation 1017 seizure blockage 911 self paced movement 529 sEMG 124 sensitivity 998 separation 178 Sequential convolution kernel compensation 105 Setup 1058 SFEAPs 118 SFS 843 shape memory alloy springs 969 shear stresses 545 Sherman-Morrison matrix inversion 105 short term variability 777

1155

ShRNA 624 signal processing 148 similarity measures 793 Simplified Ray Method 304 simulation 327, 377 Simulation 685, 716 simulator 342 single-leg jump 288 siRNA 624 skeleton 919 skin 597 skin application 453 small animal imaging 826 SMC a-Actin 242 snoring 864 social pressure situation 1034 soft palate 864 Soft tissue 308 solid tumors 582, 589 Sotalol 50 spasticity 393 specialist studies 310 spectral estimation 419 spectrometry of scattered radiation 856 Speech Recognition 1058 Spinal deformities 969 spinal implants 969 Spontaneous discharge 442 stance phase 689 standardization 401 stapedius muscle reflex 940 steopcounting 1006 stepping-in-place 262 stereotactic radiosurgery 887 Sternberg task 501 stimulus generation 202 STN 521 stroke 936, 954 structure-continual study 257 subgroup discovery 157 Suction wave 278 sudden cardiac death 22 supporting factors 157 surface electromyogram 109 Surface electromyogram 105 surface electromyography 990 surface modification 238 surgical navigation 1132 surgical robot 1132 surgical simulator 1038 Survey 1085

suspensions in blood 257 swimming 1002 swing phase 689 SWOT 762 symbolic dynamics 766, 773 Sympatho-vagal balance 30 Synchronous data acquisition 202 system dynamics 385 systemic electroporation 18

T Tactile Mapping 286 target function 762 target specificity 835 targeted therapy 1135 teaching 1126 teaching design 1142 tele-cytology 749 telediagnostics 397 Telehealthcare 712 Telemedecine 758 telemedicine 745, 749, 1006 telemetry 373 telemonitoring 397, 1006 telepathology 745, 749 temperature 570 temperature sensor 346 Tendon 308 tensiomyography 393 testing 998 Texture 843 Texture analysis 847 theory 593 three dimensional image 1132 threshold current 554 thrombolysis 859 Thrombosis 566 time domaim 278 time series 677 Time-Frequency Distribution 30 time-frequency plots 497 tissue engineering 249, 253 tissue resistance variation 198 TMG 393 tomosynthesis 826 Trabeculae 274 training 879 Training 313, 982 Training program 1074 transcranial magnetic stimulation (TMS) 643

1156

Transcutaneous Nerve Electrical Stimulation 932 transesophageal pacing 554 transformation 497 Translational research 10 transmembrane potential 635 transmural pressure 871 Treadmill Training 7 trials 1140 true three dimensional display 1132 tumor blood flow 469 tumors 453 twitch 114

U Ukraine 700 ultrasound 377, 629 Ultrasound 1021 uncertainty 338, 361 Universal Serial Bus (USB) 381 upper limb amputation 965 usability test 558 USB 58 user interaction 558 uterine electrohysterogram 144 uterus 135, 139 Uterus 128, 148 utrasonography 1025

Index Subjects

V

W

vagal blockade 26 vascular disruption 457 vascular tone 562 vasoactive compound 453 Vasomotion 932 veterinary medicine 310, 586 VHDL-AMS 377 Vibro-acoustography 1021 Video lectures 1111 videoconference 1107 vimentin 242 vinblastine 469 virtual campus 1122 virtual environment 973, 1126 Virtual environment 982 Virtual learning environment 1130 virtual mirror 262 virtual reality 1030, 1034 Virtual reality 1038 virtual rehabilitation 262 Viscoelastic properties 308 visual acuity 426 visualization 513 Visualization Interface 814 VLP-Fuzzy Clustering-HRECG 99 voltage beakdown 578 voltage commutator 574 voltage pulse plethysmography 198

wave intensity 278 wavelet 899 wavelet analysis 919 wavelet transform 70 wavelet variance 919 wax filter compensators 867 Wearable intelligent device 712 wearable systems 558 Web Service 758 Web services 693 Web-based 814 web-based management system 1092 weighted least squares 423 WHO Project 1100 Whole body vibration 990 wireless 798 Wireless Data Transmission 1058 wireless monitoring 373 working memory 501 XML 704 X-Ray 802 young adults 357

µ µCT 826