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1 ACADEMIC PRESS SERIES IN BIOMEDICAL ENGINEERING ELSEVIER ACADEMIC PRESS "mmmmmm vmnkmmwmmm'''mmmmmmmmmimmmmmmmmiinivmiv INTRODUCTION TO BIOMEDICAL ENGINEERING SECOND EDITION JOHN SUSAN foseph END ERIE BLA^HARD BRONZINO

2 This is a volume in the ACADEMIC PRESS SERIES IN BIOMEDICAL ENGINEERING Josti'H BKON/INO, SpkiF.s EDITOR Trinity College Hartford, Connecticut

3 INTRODUCTION TO BIOMEDICAL ENGINEERING Second Edition John D. Enderle University of Connecticut Storrs, Connecticut Susan M. Blanchard Florida Gulf Coast University Fort Myers, Florida Joseph D. Bronzino Trinity College Hartford, Connecticut ELSEVIER ACADEMIC Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo

4 Elsevier Academic Press 30 Corporate Drive, Suite 400, Burlington, \1A 01803, USA 525 B Street, Suite 1900, San Diego, California , USA 84 Theobald's Road, London WCIX 8RR, UK This book is printed on acid-free paper. (So) Copyright c 2005, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elscvier's Science & Technology Rights Department in Oxford, UK: phone: ( + 44) , fax: ( + 44) , permissions^"'elsevier.com.uk. You may also complete your request on-line via the Elsevier homepage (http;.'''elsevicr.com), b\' selecting "Customer Suppon" and then "Obtaining Permissions." Library of Congress Cata!oging-in-Publication Data Introduction to biomedical engineering / edited by John D. Fnderle, Joseph D. Bronzino, and Susan M. Blanchard. 1"'^ ed. p. ;cm. Includes biographical references and index. ISBN-13: ISBN-10: Biomedical engineering. [DNLM: 1. Biomedical Engineering. QT ^ ] I. Enderle, John D. (John Denis) II. Bronzino, Joseph D., III. Blanchard, Susam M. R dc British Library Cataloguing in Publication Data A catalogue record for this book is a\ailable from the British Library ISBN-13: ISBN-10: For all information on all Elsevier Academic Press publications visit our Web siteat Printed in the United States of America Working together to grow libraries in developing countries wia'w.elsevier.com ELSEVIER BOOK AID Sabre Foundation

5 This book is dedicated to our families

6 CONTENTS 1 PREFACE xiii CONTRIBUTORS TO THE FIRST EDITION xv CONTRIBUTORS TO THE SECOND EDITION xix BIOMEDICAL ENGINEERING: A HISTORICAL PERSPECTIVE Evolution of the Modern Health Care System The Modern Health Care System What Is Biomedical Engineering? Roles Played by Biomedical Engineers Professional Status of Biomedical Engineering Professional Societies 26 Exercises 28 References and Suggested Reading 29 MORAL AND ETHICAL ISSUES Morality and Ethics: A Definition of Terms 33 VII

7 Viii CONTENTS 2.2 Two Moral Norms: Beneficence and Nonmaleficence Redefining Death The Terminally III Patient and Euthanasia Taking Control Human Experimentation Definition and Purpose of Experimentation Informed Consent Regulation of Medical Device Innovation Marketing Medical Devices Ethical Issues in Feasibility Studies Ethical Issues in Emergency Use Ethical Issues in Treatment Use The Role of the Biomedical Engineer in the FDA Process 69 Exercises 70 Suggested Reading 71 ANATOMY AND PHYSIOLOGY Introduction Cellular Organization Tissues Major Organ Systems Homeostasis 119 Exercises 121 Suggested Reading 125 BIOMECHANICS Introduction Basic Mechanics Mechanics of Materials Viscoelastic Properties Cartilage, Ligament, Tendon, and Muscle Clinical Gait Analysis Cardiovascular Dynamics 186 Exercises 207 Suggested Reading 209 REHABILITATION ENGINEERING AND ASSISTIVE TECHNOLOGY Introduction 212

8 CONTENTS IX 5.2 The Human Component Principles of Assistive Technology Assessment Principles of Rehabilitation Engineering Practice of Rehabilitation Engineering and Assistive Technology 239 Exercises 243 Suggested Reading 252 BIOMATERIALS Materials in Medicine: From Prosthetics to Regeneration Biomaterials: Properties, Types, and Applications Lessons from Nature on Biomaterial Design and Selection Tissue-Biomaterial Interactions Guiding Tissue Repair with Bio-Inspired Biomaterials Safety Testing and Regulation of Biomaterials Application-Specific Strategies for the Design and Selection of Biomaterials 301 Exercises 310 Suggested Reading 311 TISSUE ENGINEERING What Is Tissue Engineering? Biological Considerations Physical Considerations Scaling Up Implementation of Tissue Engineered Products Future Directions: Functional Tissue Engineering and the "-Omics" Sciences Conclusions Glossary 393 Exercises 395 Suggested Reading BIOINSTRUMENTATION Introduction Basic Bioinstrumentation System Charge, Current, Voltage, Power, and Energy Resistance Linear Network Analysis Linearity and Superposition 432

9 CONTENTS 8.7 Thevenin's Theorem Inductors Capacitors A General Approach to Solving Circuits Involving Resistors, Capacitors, and Inductors Operational Amplifiers Time-Varying Signals Active Analog Filters Bioinstrumentation Design 484 Exercises 487 Suggested Reading n BIOMEDICAL SENSORS Introduction Biopotential Measurements Physical Measurements Blood Gases and ph Sensors Bioanalytical Sensors Optical Biosensors 539 Exercises 545 Suggested Reading 548 BIOSIGNAL PROCESSING Introduction Physiological Origins of Biosignals Characteristics of Biosignals Signal Acquisition Frequency Domain Representation of Biological Signals Linear Systems Signal Averaging Wavelet Transform and Short-Time Fourier Transform Artificial Intelligence Techniques 612 Exercises 619 Suggested Reading 624 BIOELECTRIC PHENOMENA Introduction History 629

10 CONTENTS Xi Neurons Basic Biophysics Tools and Relationships Equivalent Circuit Model for the Cell Membrane Hodgkin-Huxley Model of the Action Potential Model of the Whole Neuron 680 Exercises 684 Suggested Reading 690 PHYSIOLOGICAL MODELING Introduction Compartmental Modeling An Overview of the Fast Eye Movement System Westheimer Saccadic Eye Movement Model The Saccade Controller Development of an Oculomotor Muscle Model A Linear Muscle Model A Linear Homeomorphic Saccadic Eye Movement Model A Truer Linear Homeomorphic Saccadic Eye Movement Model System Identification 773 Exercises 788 Suggested Reading 797 GENOMICS AND BIOINFORMATICS Introduction Core Laboratory Technologies Core Bioinformatics Technologies Conclusion 828 Exercises 829 Suggested Reading 830 COMPUTATIONAL CELL BIOLOGY AND COMPLEXITY Computational Biology The Modeling Process Bionetworks Introduction to Complexity Theory 849 Exercises 852 Suggested Readings 854

11 Xii RADIATION IMAGING Introduction Emission Imaging Systems Instrumentation and Imaging Devices Radiographic Imaging Systems 882 Exercises 902 Suggested Reading 904 MEDICAL IMAGING Introduction Diagnostic Ultrasound Imaging Magnetic Resonance Imaging (MRI) Comparison of Imaging Modes 969 Exercises 972 Suggested Reading 975 BIOMEDICAL OPTICS AND LASERS Introduction to Essential Optical Principles Fundamentals of Light Propagation in Biological Tissue Physical Interaction of Light and Physical Sensing Biochemical Measurement Techniques Using Light Fundamentals of Photothermal Therapeutic Effects of Lasers Fiber Optics and Waveguides in Medicine Biomedical Optical Imaging 1033 Exercises 1039 Suggested Reading 1042 CONTENTS Appendix 1045 Index 1085