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Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page i INTRODUCTION TO BIOMEDICAL ENGINEERING Second Edition Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page ii This is a volume in the ACADEMIC PRESS SERIES IN BIOMEDICAL ENGINEERING J O S E P H B R O N Z I N O , SE R I E S E D I T O R Trinity College—Hartford, Connecticut Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page iii 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 Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page iv Elsevier Academic Press 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright ß 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 Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting ‘‘Customer Support’’ and then ‘‘Obtaining Permissions.’’ Library of Congress Cataloging-in-Publication Data Introduction to biomedical engineering / edited by John D. Enderle, Joseph D. Bronzino, and Susan M. Blanchard. —2nd ed. p. ;cm. Includes biographical references and index. ISBN 0-12-238662-0 1. Biomedical engineering. [DNLM: 1. Biomedical Engineering. QT 36 I615 2005] I. Enderle, John D. ( John Denis) II. Bronzino, Joseph D., III. Blanchard, Susam M. R856.I47 2005 610’.28—dc22 2004030223 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN: 0-12-238662-0 For all information on all Elsevier Academic Press publications visit our Web site at www.books.elsevier.com Printed in the United States of America 05 06 07 08 09 10 9 8 7 6 5 4 3 2 1 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page v This book is dedicated to our families Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page vi Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page vii CONTENTS PREFACE xiii CONTRIBUTORS TO THE FIRST EDITION xv CONTRIBUTORS TO THE SECOND EDITION xix 1 BIOMEDICAL ENGINEERING: A HISTORICAL PERSPECTIVE 1 1.1 Evolution of the Modern Health Care System 2 1.2 The Modern Health Care System 10 1.3 What Is Biomedical Engineering? 17 1.4 Roles Played by Biomedical Engineers 23 1.5 Professional Status of Biomedical Engineering 24 1.6 Professional Societies 26 Exercises 28 References and Suggested Reading 29 2 MORAL AND ETHICAL ISSUES 2.1 31 Morality and Ethics: A Definition of Terms 33 vii Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page viii viii CONTENTS 2.2 Two Moral Norms: Beneficence and Nonmaleficence 40 2.3 Redefining Death 41 2.4 The Terminally Ill Patient and Euthanasia 45 2.5 Taking Control 49 2.6 Human Experimentation 49 2.7 Definition and Purpose of Experimentation 51 2.8 Informed Consent 53 2.9 Regulation of Medical Device Innovation 59 2.10 Marketing Medical Devices 61 2.11 Ethical Issues in Feasibility Studies 63 2.12 Ethical Issues in Emergency Use 65 2.13 Ethical Issues in Treatment Use 68 2.14 The Role of the Biomedical Engineer in the FDA Process 69 Exercises 70 Suggested Reading 71 3 ANATOMY AND PHYSIOLOGY 73 3.1 Introduction 74 3.2 Cellular Organization 76 3.3 Tissues 92 3.4 Major Organ Systems 94 3.5 Homeostasis 119 Exercises 121 Suggested Reading 125 4 BIOMECHANICS 127 4.1 Introduction 128 4.2 Basic Mechanics 131 4.3 Mechanics of Materials 151 4.4 Viscoelastic Properties 159 4.5 Cartilage, Ligament, Tendon, and Muscle 4.6 Clinical Gait Analysis 169 4.7 Cardiovascular Dynamics 186 Exercises 207 Suggested Reading 209 5 REHABILITATION ENGINEERING AND ASSISTIVE TECHNOLOGY 211 5.1 Introduction 212 163 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page ix ix CONTENTS 5.2 The Human Component 218 5.3 Principles of Assistive Technology Assessment 224 5.4 Principles of Rehabilitation Engineering 227 5.5 Practice of Rehabilitation Engineering and Assistive Technology Exercises 243 Suggested Reading 252 6 BIOMATERIALS 255 6.1 6.2 6.3 6.4 6.5 6.6 6.7 Materials in Medicine: From Prosthetics to Regeneration 256 Biomaterials: Properties, Types, and Applications 258 Lessons from Nature on Biomaterial Design and Selection 276 Tissue–Biomaterial Interactions 281 Guiding Tissue Repair with Bio-Inspired Biomaterials 290 Safety Testing and Regulation of Biomaterials 296 Application-Specific Strategies for the Design and Selection of Biomaterials 301 Exercises 310 Suggested Reading 311 7 TISSUE ENGINEERING 313 7.1 7.2 7.3 7.4 7.5 7.6 What Is Tissue Engineering? 314 Biological Considerations 331 Physical Considerations 360 Scaling Up 382 Implementation of Tissue Engineered Products 386 Future Directions: Functional Tissue Engineering and the ‘‘-Omics’’ Sciences 390 7.7 Conclusions 393 7.8 Glossary 393 Exercises 395 Suggested Reading 400 8 BIOINSTRUMENTATION 8.1 8.2 8.3 8.4 8.5 8.6 403 Introduction 404 Basic Bioinstrumentation System 407 Charge, Current, Voltage, Power, and Energy Resistance 415 Linear Network Analysis 425 Linearity and Superposition 432 408 239 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page x x CONTENTS ´ 8.7 Thevenin’s Theorem 436 8.8 Inductors 439 8.9 Capacitors 442 8.10 A General Approach to Solving Circuits Involving Resistors, Capacitors, and Inductors 446 8.11 Operational Amplifiers 455 8.12 Time-Varying Signals 468 8.13 Active Analog Filters 474 8.14 Bioinstrumentation Design 484 Exercises 487 Suggested Reading 504 9 BIOMEDICAL SENSORS 505 9.1 Introduction 506 9.2 Biopotential Measurements 508 9.3 Physical Measurements 513 9.4 Blood Gases and pH Sensors 527 9.5 Bioanalytical Sensors 536 9.6 Optical Biosensors 539 Exercises 545 Suggested Reading 548 10 BIOSIGNAL PROCESSING 549 10.1 Introduction 550 10.2 Physiological Origins of Biosignals 551 10.3 Characteristics of Biosignals 554 10.4 Signal Acquisition 557 10.5 Frequency Domain Representation of Biological Signals 562 10.6 Linear Systems 584 10.7 Signal Averaging 597 10.8 Wavelet Transform and Short-Time Fourier Transform 605 10.9 Artificial Intelligence Techniques 612 Exercises 619 Suggested Reading 624 11 BIOELECTRIC PHENOMENA 11.1 11.2 Introduction 628 History 629 627 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xi xi CONTENTS 11.3 Neurons 637 11.4 Basic Biophysics Tools and Relationships 642 11.5 Equivalent Circuit Model for the Cell Membrane 653 11.6 Hodgkin–Huxley Model of the Action Potential 664 11.7 Model of the Whole Neuron 680 Exercises 684 Suggested Reading 690 12 PHYSIOLOGICAL MODELING 693 12.1 Introduction 694 12.2 Compartmental Modeling 698 12.3 An Overview of the Fast Eye Movement System 723 12.4 Westheimer Saccadic Eye Movement Model 728 12.5 The Saccade Controller 735 12.6 Development of an Oculomotor Muscle Model 738 12.7 A Linear Muscle Model 751 12.8 A Linear Homeomorphic Saccadic Eye Movement Model 757 12.9 A Truer Linear Homeomorphic Saccadic Eye Movement Model 763 12.10 System Identification 773 Exercises 788 Suggested Reading 797 13 GENOMICS AND BIOINFORMATICS 799 13.1 Introduction 800 13.2 Core Laboratory Technologies 804 13.3 Core Bioinformatics Technologies 812 13.4 Conclusion 828 Exercises 829 Suggested Reading 830 14 COMPUTATIONAL CELL BIOLOGY AND COMPLEXITY 14.1 Computational Biology 834 14.2 The Modeling Process 835 14.3 Bionetworks 846 14.4 Introduction to Complexity Theory Exercises 852 Suggested Readings 854 849 833 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof xii 15 CONTENTS RADIATION IMAGING 857 15.1 Introduction 858 15.2 Emission Imaging Systems 859 15.3 Instrumentation and Imaging Devices 15.4 Radiographic Imaging Systems 882 Exercises 902 Suggested Reading 904 16 5.2.2005 1:21pm page xii MEDICAL IMAGING 876 905 16.1 Introduction 906 16.2 Diagnostic Ultrasound Imaging 908 16.3 Magnetic Resonance Imaging (MRI) 940 16.4 Comparison of Imaging Modes 969 Exercises 972 Suggested Reading 975 17 BIOMEDICAL OPTICS AND LASERS 977 17.1 Introduction to Essential Optical Principles 979 17.2 Fundamentals of Light Propagation in Biological Tissue 985 17.3 Physical Interaction of Light and Physical Sensing 997 17.4 Biochemical Measurement Techniques Using Light 1006 17.5 Fundamentals of Photothermal Therapeutic Effects of Lasers 1015 17.6 Fiber Optics and Waveguides in Medicine 1026 17.7 Biomedical Optical Imaging 1033 Exercises 1039 Suggested Reading 1042 Appendix 1045 Index 1085 Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xiii PREFACE The purpose of the second edition remains the same as the first edition: that is, to serve as an introduction to and overview of the field of biomedical engineering. Many chapters have undergone major revision from the previous edition with new endof-chapter problems added. Some chapters were combined and some chapters were eliminated completely, with several new chapters added to reflect changes in the field. Over the past fifty years, as the discipline of biomedical engineering has evolved, it has become clear that it is a diverse, seemingly all-encompassing field that includes such areas as bioelectric phenomena, bioinformatics, biomaterials, biomechanics, bioinstrumentation, biosensors, biosignal processing, biotechnology, computational biology and complexity, genomics, medical imaging, optics and lasers, radiation imaging, rehabilitation engineering, tissue engineering, and moral and ethical issues. Although it is not possible to cover all of the biomedical engineering domains in this textbook, we have made an effort to focus on most of the major fields of activity in which biomedical engineers are engaged. The text is written primarily for engineering students who have completed differential equations and a basic course in statics. Students in their sophomore year or junior year should be adequately prepared for this textbook. Students in the biological sciences, including those in the fields of medicine and nursing, can also read and understand this material if they have the appropriate mathematical background. Although we do attempt to be fairly rigorous with our discussions and proofs, our ultimate aim is to help students grasp the nature of biomedical engineering. Therefore, we have compromised when necessary and have occasionally used less rigorous mathematics in order to be more understandable. A liberal use of illustrative examples amplifies concepts and develops problem-solving skills. Throughout the text, MATLAB1 (a matrix equation solver) and SIMULINK1 (an extension to MATLAB1 xiii Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof xiv 5.2.2005 1:21pm page xiv PREFACE for simulating dynamic systems) are used as computer tools to assist with problem solving. The Appendix provides the necessary background to use MATLAB1 and SIMULINK1. MATLAB1 and SIMULINK1 are available from: The Mathworks, Inc. 24 Prime Park Way Natick, Massachusetts 01760 Phone: (508) 647-7000 Email: [email protected] WWW: http://www.mathworks.com {extend} Chapters are written to provide some historical perspective of the major developments in a specific biomedical engineering domain as well as the fundamental principles that underlie biomedical engineering design, analysis, and modeling procedures in that domain. In addition, examples of some of the problems encountered, as well as the techniques used to solve them, are provided. Selected problems, ranging from simple to difficult, are presented at the end of each chapter in the same general order as covered in the text. The material in this textbook has been designed for a one-semester, two-semester, or three-quarter sequence depending on the needs and interests of the instructor. Chapter 1 provides necessary background to understand the history and appreciate the field of biomedical engineering. Chapter 2 presents the vitally important chapter on biomedically-based morals and ethics. Basic anatomy and physiology are provided in Chapter 3. Chapters 4-10 provide the basic core biomedical engineering areas: biomechanics, rehabilitation engineering, biomaterials, tissue engineering, bioinstrumentation, biosensors, and biosignal processing. To assist instructors in planning the sequence of material they may wish to emphasize, it is suggested that the chapters on bioinstrumentation, biosensors, and biosignal processing should be covered together as they are interdependent on each other. The remainder of the textbook presents material on biomedical technology (Chapters 12-17). A website is available at http://intro-bme-book.bme.uconn.edu/ that provides an errata and extra material. ACKNOWLEDGEMENTS Many people have helped us in writing this textbook. Well deserved credit is due to the many contributors who provided chapters and worked under a very tight timeline. Special thanks go to our publisher, Elsevier, especially for the tireless work of the editors, Christine Minihane and Shoshanna Grossman. In addition, we appreciate the work of Karen Forster, the project manager, and Kristin Macek, who supervised the production process. A great debt of gratitude is extended to Joel Claypool, the editor of the first edition of the book and Diane Grossman from Academic Press. From an initial conversation over coffee in Amsterdam in 1996 to publication in 2000 required a huge effort. Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xv CONTRIBUTORS TO THE FIRST EDITION Susan M. Blanchard Florida Gulf Coast University Fort Myers, Florida Joseph D. Bronzino Trinity College Hartford, Connecticut Stanley A. Brown Food and Drug Administration Gaithersburg, Maryland ´ Gerard Cote Texas A&M University College Station, Texas Roy B. Davis III Shriners Hospital for Children Greenville, South Carolina John D. Enderle University of Connecticut Storrs Connecticut xv Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof xvi 5.2.2005 1:21pm page xvi CONTRIBUTORS TO THE FIRST EDITION Robert J. Fisher University of Massachusetts Amherst, Massachusetts Carol Lucas University of North Carolina Chapel Hill, North Carolina Amanda Marley North Carolina State University Raleigh, North Carolina Yitzhak Mendelson Worcester Polytechnic Institute Worcester, Massachusetts Katharine Merritt Food and Drug Administration Gaithersburg, Maryland H. Troy Nagle North Carolina State University Raleigh, North Carolina Joseph Palladino Trinity College Hartford, Connecticut Bernhard Palsson University of California at San Diego San Diego, California Sohi Rastegar National Science Foundation Arlington, Virginia Daniel Schneck Virginia Polytechnic Institute & State University Blacksburg, Virginia Kirk K Shung Pennsylvania State University University Park, Pennsylvania Anne-Marie Stomp North Carolina State University Raleigh, North Carolina Andrew Szeto San Diego State University San Diego, California Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof CONTRIBUTORS TO THE FIRST EDITION LiHong Wang Texas A&M University College Station, Texas Steven Wright Texas A&M University College Station, Texas Melanie T. Young North Carolina State University Raleigh, North Carolina 5.2.2005 1:21pm page xvii xvii Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xviii Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xix CONTRIBUTORS TO THE SECOND EDITION Susan M. Blanchard Florida Gulf Coast University Fort Myers, Florida Joseph D. Bronzino Trinity College Hartford, Connecticut Stanley A. Brown Food and Drug Administration Gaithersburg, Maryland ´ Gerard Cote Texas A&M University College Station, Texas Charles Coward Drexel University Philadelphia, Pennsylvania Roy B. Davis Shriners Hospital for Children Greenville, South Carolina xix Enderle / Introduction to Biomedical Engineering 2nd ed. Final Proof 5.2.2005 1:21pm page xx xx CONTRIBUTORS TO THE SECOND EDITION Robert Dennis University of North Carolina Chapel Hill, North Carolina John D. Enderle University of Connecticut Storrs, Connecticut ´ Monty Escabı University of Connecticut Storrs, Connecticut R.J. Fisher University of Massachusetts Amherst, Massachusetts Liisa Kuhn University of Connecticut Health Center Farmington, Connecticut Carol Lucas University of North Carolina Chapel Hill, North Carolina Jeffrey Mac Donald University of North Carolina Chapel Hill, North Carolina Amanda Marley North Carolina State University Raleigh, North Carolina Randall McClelland University of North Carolina Chapel Hill, North Carolina Yitzhak Mendelson Worcester Polytechnic Institute Worcester, Massachusetts Katharine Merritt Food and Drug Administration Gaithersburg, Maryland Spencer Muse North Carolina State University Raleigh, North Carolina H. Troy Nagle North Carolina State University Raleigh, North Carolina
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