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: permissions@elsevier.com.uk 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 Biomedical engineering [DNLM: 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 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 BIOMEDICAL ENGINEERING: A HISTORICAL PERSPECTIVE 1.1 Evolution of the Modern Health Care System 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 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 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 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 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 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 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 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 2.2.2005 7:17pm page 1104 1104 Material phase, 988–990 Materials mechanics of, 151–159 Mathematica, 1022 MATLAB, 1045–1083 arithmetic expressions in, 1051–1052 block diagrams in, 1069–1071 blood power law fit in, 189–190 compact Fourier series in, 569 complex numbers in, 1053–1055 cross products in, 1053 diff command, 1065 differential equations with, 1064–1069 dot products in, 1053 dsolve command, 1067–1069 Euler angle transformation matrices in, 140–143 exponential Fourier series in, 571–572 exponential function in, 1050 ezplot command, 1067 format long in, 1058–1059 fplot in, 1060–1061 GK and GNa equations in, 673 int command, 1065, 1066 isovolumic pressure and, 198–200 laser heating in, 1022 loading and saving the workspace in, 1064 matrix basics and, 1045–1048 modeling in, 836–837 P in, 1050 plot in, 1061 plotting axial force with, 157–158 plotting with, 1060–1063 plotting with Excel in, 1061–1063 polynomials and roots in, 1055–1059 roots command, 1066 signal averaging in, 603–604 SIMULINK in, 1069–1083 simultaneous equations and matrices and, 1047–1048 solve command, 1066–1067 starting, 1048–1050 suppressing command echo in, 1056 suppressing printing in, 1050 Symbolic Math Toolbox, 1064–1069 system identification in, 781 INDEX trigonometric Fourier series in, 565–567 trigonometric functions in, 1051 using, 1048–1050 vector mathematics in, 135–137 vectors in, 1052–1053 wavelet analysis in, 610–611 windows in, 1048, 1049 Matrices addition of, 1046, 1047 basics on, 1045–1048 BLOSUM, 819 identity, 1046 Mueller, 982 multiplication of, 1046, 1047 null, 1046 PAM, 819 simultaneous equations and, 1047–1048 square, 1047 subtraction of, 1046, 1047 Matrix Laboratory See MATLAB Matteucci, Carlo, 635–636 Maturational lineage, 318, 333–338 bone marrow/blood cell, 334–335 examples of stem cell–fed, 334–338 liver cells, 337–338 mesenchymal stem cells, 336–337 skin cells, 336 small intestine villi, 335 Maxwell, James Clerk, 160, 161, 443, 979 Maxwell model of viscoelastic properties, 159, 160–161, 162 Maxwell’s equations, 979–982, 987 MBSL See multiple-bubble sonoluminescence (MBSL) McClelland, Randall, 313–401 McDonald, I., 912 Measles, 708 Measurands, definition of, 407 Measurement biochemical techniques of, 1006–1015 in compartmental modeling, 701 error, in models, 696 of inductance, 440 luminescense and, 1011–1012 microarrays and, 827 of optical properties, 994–997 polarization and, 1012–1014 of radiation, 874–876 signal averaging and, 597–604 Mechanid der meschlichen Gerwerkzeuge, Die (On the Mechanics of the Human Gait) (Weber,Weber), 131 Media, 305 Medial position, 74–75 Medial rectus, 723 Medicaid, assistive technology and, 216 Medi-Cal, 239 Medical Device Amendment of 1976, 60 Medical devices classes of, 300 emergency use of unapproved, 65–68 FDA definition of, 60–61 FDA regulation of, 59–61, 300–301 feasibility studies, 63–65 marketing, 61–63 off-label use of, 301 reporting requirements for, 69–70 risk levels and, 62 Medical education early, 7–8 Medical imaging, 905–975 See also computerized tomography (CT); xrays comparison of modes in, 969–972 computerized tomography, 971–972 Fourier transforms and, 907–908 frequently used, 906–907 magnetic resonance, 940–969, 973 optical techniques for, 1033–1039 radiation-based, 857–904 ultrasound, 908–940, 971 Medical Internal Radiation Dose (MIRD) Committee, 876 Medical records, privacy and, 58–59 Medicare, assistive technology and, 216 Medulla oblongata, 110 Medullary cavity, 112 Membrane potentials, 639–640 See also action potentials changes in with distance, 662–664 Donnan equilibrium and, 645–647 Goldman equation and, 648–651 neuron capacitance and, 659–662 time dependence equation for, 675–679 Memory, computer, 486 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1105 1105 INDEX Mendelson, Yitzhak, 505–548 Mercury amalgams, 276 Mercury cadmium teluride (MCT), 1007 Mesenchymal stem cells, 277 cellularity and, 376 epithelial relationship with, 326–327 maturational lineage and, 336–337 vascular grafts and, 323 Mesh, circuit, 411 Mesoderm, 345 Messenger RNA (ribonucleic acid), 88, 803 cell modeling and, 834–835 decay rate of, 846 protein production modeling and, 845–846 in transcription, 88–89 in translation, 90–91 Metabolism ATP in, 77 compartmental modeling and, 698–722 complexity in, 851–852 microenvironment and, 379 modeling pathways of within cells, 835 Metacarpophlangeal joints, 113 Metallic wire strain gauges, 519–520 Metal plates, 262, 266 Metals advantages/disadvantages of, 268 as biomaterials, 262–269 corrosion of, 283–287 half-cell potentials of, 508–510 immunogenicity and, 289 in microelectrodes, 512, 513 Metastable state, 864 Methionine, 90 Michaelis–Mentin equation, 838–840 Michelson interferometer, 1002–1006 Microarrays cDNA, 808–811 gene clustering and, 827–828 gene expression and, 807–811 gene identification and, 826–827 two-treatment experiments with, 826–827 Microbial biosensors, 538–539 Micro-CT, 297–298 Microcuries, 872 Microelectrodes, 512–513 Microenvironments, 363–365, 371–381 cellular function and, 372–375 cellularity and, 375–377 dynamics of, 377–380 geometry of, 380–381 oxygenation in, 377–379 size of, 381 Microfibrils, 280, 281 Microfilaments, 85, 87 Micrometers, 1014–1015 Micropatterning, 293 Microscopes atomic force, 297 development of, 76–77 electron, 12 scanning electron, 297 Microsoft Excel, 836–837, 1048, 1061–1063 Microtubules, 85, 87 Midbrain, 110 Midsaggital plane, 74, 76 milieu-dependent differentiation, 354–355 Millicuries, 872 Milliroentgens, 875 MIRD See Medical Internal Radiation Dose (MIRD) Committee Mitochondria, 78, 85, 86 Mitogen-activated protein kinase (MAPK) pathway, 844–845 Mitotic clock, 340 Mitral valve, 96, 99 Mobility, Einstein relationship and, 644 Modeling assumptions in, 835 cardiovascular, 200–207 of cellular processes, 834 compartmental, 698–722 computation time for, 835 of control mechanisms within cells, 834–835 data input for, 735–738 deterministic, 696 equations of, 837–846 metabolic pathways, 835 physiological, 693–798 process of, 835–846 purpose of, 835 signal transduction, 840–845 solutions in, 696–698 steps in, 695–696 stochastic, 696 system identification in, 771–787 Modified compartmental modeling, 708–717 Modulus of rigidity, 153–154 Moles, 862 Moment of force, 134–135 Moment of inertia, eyeball, 758–759 Monocytes, 277 cellularity and, 376 Monte Carlo method, 992, 995 Morality, 33–34 See also ethics Morals, 33 See also ethics Mores, 33 Motility, cell, 343 Motion, equations of, 150–151 arterial vessels and, 191 arterial walls and, 192–193 Euler’s, 150–151 Navier-Stokes, 192 Newtonian fluids and, 191–192 Newton’s, 143–147, 150 vector, 150–151 Motor nerve endings, muscle contraction and, 118–119 Motor units, 119 Movement control, 220 Moving coordinate systems, 137–138, 139 MRI See magnetic resonance imaging (MRI) Mueller matrices, 982 Mulier ventricle model, 198–200 Multicompartmental models, 705–708 See also compartmental modeling Multiflux models, 992 Multigene families, 825 Multilayered perceptrons, 618 Multiple-bubble sonoluminescence (MBSL), 1038–1039 Multiple sclerosis, 233 Muscles active-state tension generators and, 738–739, 740–741 force–velocity relationship in, 745–751, 756–757 linear model of, 751–757 oculomotor muscle model, 738–751 passive elasticity of, 738–739 saccades and tension in, 737–738 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1106 1106 Muscle tissue, 92–93 biomechanics of, 163, 166–169 static equilibrium and, 145–146 types of, 93, 116 Muscular dystrophies, 233 Muscular system, 94–101, 113–119 lever system in, 115–116 muscle contraction and, 116–118 skeletal, 113–114 Musculoskeletal repair, 301–303 Musculoskeletal system, 363 Muse, Spencer, 799–831 Mutations, 817 Myelin sheaths, 107, 108 Myoablation, 394 Myofibrils, 117 muscle, 117 Myofilaments, 87 muscle, 117 Myosin, 87 muscle contraction and, 117–118 N Na+ conductance gates, 664–665 Nader, Ralph, 20 Na-K pumps, 651–653, 657 Nanometers, 1014–1015 Nasal cavity, 75 National Center for Biotechnology Information (NCBI), 813, 815, 825 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 52 National Fire Protection Association (NFPA), 20 National Institute for Handicapped Research, 214 National Institute on Disability and Rehabilitation Research (NIDRR), 214 Rehabilitation Engineering Centers, 216–217 National Institutes of Health, 268 National Science Foundation (NSA), 215 Natural focal length, 934 Natural response, 469 Navier-Stokes equations, 192 NCBI See National Center for Biotechnology Information (NCBI) Near-infrared wavelengths, 1007–1008 INDEX Necrosis, 278, 318 lasers and, 1018–1019 Needleman–Wunsch algorithm, 818 Negation operator, 613, 614 Negative feedback, in homeostasis, 120–121, 122 Negative pressure ventilators, 106 Negatron decay, 868–869 Neocortical death, 44–45 Neonatal intensive care units (NICUs), 50–51 Neovascularization, 294 Nernst, Walter, 645 Nernst equation, 645 ion pumps and, 652 Nernst potentials Donnan equilibrium and, 645–647 electromotive force properties and, 654 equivalent circuit for three ions and, 657 in frog skeletal muscle, 651 in squid giant axons, 650 voltage clamp experiment and, 671 Nerve cells See neurons Nervous system, 94–101, 106–110, 363 autonomic, 106–107 central, 106 muscle contraction and, 118–119 neurogenesis in, 278 peripheral, 106 somatic, 106–107 Nervous tissue, 92–93 Network theory, 921 Neural networks, 612, 616–619 gene prediction and, 824 Neurogenesis, 278 Neuroglia, 109 resting potential of membranes permeable to one ion and, 644–645 Neurons, 13, 107, 637–642 action potentials in, 637, 639–640 capacitance of, 658–662 channels in, 640–641 connections among, 108 graded response in, 639–640 interaction between adjacent, 681–683 ion concentrations in, 640–641 membrane potentials and, 639–640 model of whole, 680–684 in nervous tissue, 93 in neural networks, 616–619 numbers of, 637–638 regions of, 638 resting potentials in, 640–641 sensory, 106 stem cell therapies, 326 Neurotransmitters, 107 as current pulses, 662 in graded response and action potentials, 639–640 muscle contraction and, 118–119 Neutrinos, 868–869, 870 Neutrons, 861–863 negatron decay and, 868–869 Neutrophils, 277 cellularity and, 376 motility of, 351, 352, 380 in wound healing, 346 Newton, Isaac, 130 Newtonian fluids, 188–190 equations of motion for, 191–192 Newtons, 258 Newton’s equations of motion, 150 static equilibrium and, 143–147 NFPA See National Fire Protection Association (NFPA) Niche hypothesis, 331–333 NIDRR See National Institute on Disability and Rehabilitation Research (NIDRR) Nightingale, Florence, 8, Nimura, Y., 911 Nitinol, 268–269 Nitrobacter biosensors, 538 nitrogen dioxide, microbial biosensors for, 538, 539 Nitrosomonas biosensors, 538 Nobel Prizes, 11 Nodes, circuit, 410 essential, 411 node-voltage method and, 426–432 supernodes, 430–432 Nodes of Ranvier, 108, 638 action potentials and, 665 in whole neuron model, 680 Node-voltage method, 426–432 initial conditions and, 451–455 phasor domain and, 472 solving circuits in, 448 Noise bioinstrumentation and, 485 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1107 1107 INDEX in biological signal acquisition, 557–558 biosignals and, 555 inherent, 485 signal averaging and, 597–604 sources of, 485 Nonconjugate eye movements, 723–724 Nonconsequentialism, 34–35 Nonionizing optical tomography, 1035–1037 Nonlinear Hill hyperbola, 749–751 Nonmaleficence, 40–41 Non-Newtonian fluids, 188 Nontherapeutic research, 52 informed consent for, 56–59 Nonvalidated practice, 52 emergency use and, 65–68, 69 informed consent and, 52–59 treatment use and, 68–69 Noordergraaf viscoelastic model, 163 Norm, 132 Normal incidence video reflectometry, 995 Normative judgments, 34 Northern blot procedure, 807 Notch filters, 474, 475 Notices of Limited Investigation, 63 NP-complete problems, 819 Nuclear binding energy, 864–865 Nuclear de-excitation, 869 Nuclear envelope, 78, 84 Nuclear fission, 871 Nuclear magnetic resonance (NMR) imaging, 940–941 See also magnetic resonance imaging (MRI) biomaterials testing and, 297–298 Nuclear medicine, 12 definition of, 859 emission imaging and, 859–876 Nuclear pores, 84–85 Nuclear Regulatory Commission, 876 Nucleic acids, cellular organization and, 77 Nucleoli, 78, 84–85 Nucleons, movement of, 864 Nucleoplasm, 78, 84–85 Nucleotides, 77 codons and, 89–90 complementary base pairs, 88–89 gene sequencing and, 805–806 indels and, 817, 818 polymorphisms and, 811–812 Nuclides, 863 binding energy and, 864–865 classification of radionuclides, 866 stability of, 864–866 Null matrix, 1046 Numerical apertures, 1030 Nursing, 7–8 codes of ethics in, 38–39 Nylon, 263 Nyquist’s theorem, 560–561 O Oblique incidence reflectometry, 995–996 Oblique waves, 916–918 Occipital lobes, 109 OCT See optical-coherence tomography (OCT) Oculomotor muscle model, 738–751 active-state tension generator in, 740–741 elasticity in, 741–745 force–velocity relationship in, 745–751 length–tension elastic elements in, 744–745 linear, 751–757 passive elasticity in, 738–739 Oculomotor system, 723 ODE See Office of Device Evaluation (ODE) ode45 algorithm, 1074–1075 Office of Compliance, 60 Office of Device Evaluation (ODE), 60 Office of Health and Industry Programs, 60 Office of Science and Technology, 60 Office of Special Education and Rehabilitation Services, 215–216 Office of Surveillance and Biometrics, 60 Office of Systems and Management, 60 Offset yield, 260 Ohms, 415 Ohm’s law, 415, 643 conductance and, 416 Okazaki fragments, 340 Oligonucleotide arrays, 809–810 advantages/disadvantages of, 810–811 gene identification and, 826–827 Onaral, Banu, 833–855 Online resources COGs, 825 genome, 816 Kyoto Encyclopedia of Genes and Genomes, 848 PFAM, 825–826 On the Attractive Force of the Electric Fire (Volta), 634 Open-heart surgery, 42 Operating points, 739 Operating range, sensor, 507 Operational amplifiers (op amps), 455–467 for biological signal acquisition, 558 common-mode rejection and, 463 definition of, 455 differential, 461–463 differentiating and integrating, 464–466 dual-in-line package, 456–457 ideal, 459–460 input–output relationships in, 457–459 input terminals on, 456–457 power supply terminals on, 456–457 summing circuits and, 460–461 voltage characteristics of, 467–468 Optical-coherence tomography (OCT), 1037 Optical fibers, 539–541 Optical polarization, 982–983 Optical sensors, 539–545 indicator-mediated fiber optic, 542–543 oxygen measurement with, 532 sensing mechanisms in, 541–542 Optical tomographic imaging, 1035–1037 ultrasound-modulated, 1037–1038 Optic nerve, 723 Optics See biomedical optics Optokinetic eye movements, 723 Optrodes, 998 Oral cavity, 75 Orbital angular momentum, 942 Orbital cavity, 75 Ordered bundles, 1029–1031 Organelles, 77–78, 84–87 Organic compounds, 77 Organs Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1108 1108 Organs (continued ) artificial, 13, 53–54, 99, 100, 113 definition of, 94 extracorporeal bioartificial, 318–319 functional subunits of, 328 Organ systems, 94–119, 363 circulatory, 94–101 definition of, 94 modeling, 584–585 muscular, 113–119 nervous, 106–110 respiratory, 101–106 skeletal, 111–113 Orthogonal coordinate systems, 138, 140–143 Orthopedic bone plates, mechanics of, 151–153, 154–159 Orthotics See also assistive technology definition of, 212 WWII and, 213–214 Oscillometric method, 100 Oscilloscopes, 877 Osmolarity cell volume and, 80–82 definition of, 80 Osmosis Einstein relationship and, 644 plasma membrane and, 79–80 Osteoblasts, 112, 277, 281 Osteoclasts, 112, 277 Osteogenesis imperfecta, 233 Osteons, 280 Osteoporosis, 112 Output displays, 408 Output layer, 616 Oxidase, 536–537 Oxide films, 286 Oximetry, 531–534 pulse, 532, 534 Oxygenation biochemical measurement of, 1006–1015 fMRI and, 968–969 measuring, 528–534, 996–997 microenvironment, 377–379 penetration distances and, 381 scaling up and, 382, 383 Oxygen uptake rate (OUR), 378 Oxygen uptake rates, 383 Oxyhemoglobin, oxygen measurement and, 528–534 INDEX P Pacemaker cells, 95, 97 Pacemakers, 405 Palladino, Joseph L., 127–210 Palsson, Bernard, 313–401 PAM matrix, 819 Pancreatic islet cells, drug delivery and, 309–310 Paracine factors, 327 Parallel axis theorem, 179–180 Paramagnetic media, 967 Parameterized images, 940 Parasympathetic nervous system, 106–107 Parenchyma, 305 liver and, 337 Parent elements, 866 in alpha decay, 866–867 Parietal lobes, 109 Partial least squares (PLS) method, 1010 Partial pressure, 102 Particulate leaching, 295 Passive channels, 641–642 Passive circuit elements, 414 Passive elasticity, 738–739, 740–741 linear muscle model and, 751–757 Passive euthanasia, 46–47, 48–49 Paths, circuit, 411 Patient throughput, 902 Pauli, Wolfgang, 863, 868 Peak overshoot time, 786 Peak velocity in saccades, 725, 726, 727 Pelvic anatomical coordinate system, 170–173 Penicillin, 10–11, 318 Pennsylvania Hospital, Peptides bonds in, 90–91 self-assembly of, 279 Perception, 220 Performance inspections, 20–21 Performance specifications, 695 Performance standards, 243 Perfusion rates, 367–369 microenvironment and, 373–374, 379 scaling up and, 382 Periodic biosignals, 555 trigonometric Fourier series for, 562–567 Periodogram averaging method, 601–602 Peripheral nervous system, 106 Peripheral resistance, 193 Permeability of cell membranes, 654 Persistent signaling, 328 PET See positron emission tomography (PET) PFAM (Protein Family) database, 825–826 Phase, linear systems and, 587 Phased arrays, 927–928 Phase separation/emulsification, 295–296 Phasors, 469 Kirchhoff ’s laws and, 472–474 passive circuit elements and, 470–472 PHB See polyhydroxybutyrate (PHB) PHBHV See polyhydroxybutyrate hydroxyvalerate (PHBHV) PHEMA See polyhydroxyethylmethacrylate (PHEMA) Phenotypes, 828 Phenylalanine, 92 Phospholipids plasma membrane, 79 as surfactants, 102 Phosphorescence, 984 See also luminescence Phosphorylation, 840–845 protein production modeling and, 845–846 Photoacoustic tomography, 1038 Photography, 876 Photolithography, 293 Photomultiplier tubes, 877 Photomultiplier tubes (PMTs), 1012 Photon phase, 988–990 Photons density waves of, 1037 detectors of, 896, 898 early-photon imaging and, 1036 measurement systems and, 1011–1012 spin states and, 945 temperature generation and absorption of, 999–1000 Photorecetive cells, 724 Photothermal ablation, 1019 Phred, 806 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1109 1109 INDEX pH sensors, 527–528, 534–535 Physicians, shortages/maldistribution of, 14 Physiological modeling, 693–798 compartmental, 698–722 data input for, 735–738 deterministic models in, 696 experimental design and, 694–695 qualitative, 694 quantitative, 694 of saccadic eye movement, 723–771 solutions in, 696–698 stochastic models in, 696 system identification in, 771–787 Physiology, 73–125 cellular organization and, 76–92 definition of, 74 homeostasis and, 119–121, 122 organ systems in, 94–119 tissues and, 92–93 Picture files, 888 Piezoelectric principle, 522–523 transducers and, 918 Piezoelectric transducers, 522–524 Pineal body, 110 Pin spotting, 808 Pivot joints, 114 Pixels, 886 Plane tomography, 884 Plane waves, 913 Plank’s constant, 945 Plantar flexed ankle position, 183–184 Plasma, 187 compartmental modeling and, 698 Plasma membranes, 77–78, 79–84 cardiac cycle and, 97 cell volume regulation and, 80–82 electrical balance and, 82–84 functions of, 79 muscle, 117 permeability of, 79–80 Plasmapheresis, 392 Plasmodium falciparum, 800 Plasmons definition of, 544 surface plasmon resonance sensors and, 544–545 Plastic region of curves, 260 Platelets, 187, 282 Platinum, as biomaterial, 263, 264 Plethysmography, 517–518 PLGA, degradation/resorption of, 287–288 PLLA, degradation/resorption of, 287–288 Plotting with Excel, 1061–1063 with fplot, 1060–1061 in MATLAB, 1060–1063 with plot, 1061 Pluripotent stem cells, 331, 333 PMA See premarket approvals (PMAs) PMMA See polymethylmethacrylate (PMMA) Poisson’s ratio, bone modulus of rigidity and, 153–154 Polarimetry, 1013–1014 Polarity, 413–414 Polarization capacitors and, 442–446 measurements using, 1012–1014 optical, 982–983 Polarography, oxygen sensors and, 529–531 Poly acetal, 306–307 Poly-A tail, 88 Polyester, 263 Polyethylene glycol (PEG), 307 Polyethylene (PE), 263 carbon fiber reinforced, 275 oxides, 292 Polyhydroxybutyrate hydroxyvalerate (PHBHV), 295–296 Polyhydroxybutyrate (PHB), 274 Polyhydroxyethylmethacrylate (PHEMA), 273 Polymerization, 272 Polymers advantages/disadvantages of, 272 as biomaterial, 263, 264 biopolymers, 274–275 drug delivery and, 308 sensor packaging and, 508 Polymethylmethacrylate (PMMA) as biomaterial, 263, 264 mechanical properties of, 153 as thermoplastic, 272, 273 Polymorphisms, 811–812 definition of, 804 silent, 811–812 single nucleotide, 811–812 synonymous, 811–812 Polynomials, in MATLAB, 1055–1059 Polyoxymethylene (POM), 306–307 Polysaccharides, as biomaterials, 274 Polyvinylchloride (PVC), 263, 273 Pons, 110 Pore size, 294 pO2 sensors, 529–531 Positioning, principle of proper, 231–232, 233 conditions requiring, 233 Positive feedback, in homeostasis, 120 Positive pressure ventilators, 106 Positron decay, 869–870 Positron emission tomography (PET), 881–882, 1033 Positron-emitting transaxial tomography, 881–882 Positron imaging, 881–882 Positrons, 869–870 Posterior position, 74, 75 Posterior-superior-iliac-spine (PSIS) system, 170–173 Potassium cellular concentrations of, 80 conductance waveform, 674 ions, Goldman equation and, 648–649, 650–651 Povit joints, 113 Power, circuits and, 413–414 resistors and, 417–419 Power Doppler, 939 Power law exponents, 932–933 Power law functions, blood and, 188–190 Poynting vector, 981 Practice, research vs., 52 Precession, 947–956, 961 Preconditioned materials, 166 Premarket approvals (PMAs), 60, 301 marketing and, 61 Pressure, centers of, 178–182 Pressure deactivation, 202 Pressure–volume work loops, 205–207 Presynaptic terminals, 107, 638 in whole neuron model, 680–684 Preterm infants, 50–51 Prime movers, 114 Principal quantum numbers, 863 Principles of Dynamics (Greenwood), 131 Principles of Medical Ethics, 37–38 Prisms, 985 Privacy, 58–59 Probabilistic reasoning, 612 Probes, 1031–1033 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1110 1110 Problem solving, 23 Proceedings of the Bologna Academy, 629 Product development protocols (PDPs) marketing and, 62 Product formation velocity, 838–839 Professional Engineers (PEs), 241 Professionalization, 24–26 medical, prestige of, 11 Professional societies, 26–28 Programming languages, 486, 836–837 Prokaryotic cells, 78 Promoters, 846, 847 Proportionality constants, 523 Prosthetics See also assistive technology biomaterials and, 256–258 definition of, 212 dental root, 262, 267 WWII and, 213–214 Protective reflexes, 108 Proteins adsorption of, 290–292 biomaterial interactions with, 281–282 as biomaterials, 274 biomaterial surface chemistry modifications and, 290, 291 cell communication and, 355–358 cellular organization and, 77 clotting factor XII, 282 COGs database on, 825–826 extracellular matrix, 328 maximal secretion rates of, 356–357 one gene, one protein rule and, 803, 804 PFAM database on, 825–826 plasma membrane, 79 production of, modeling, 845–846 ribosomes and, 85 synthesis of, 85 Proteoglycans, 328 Protons, 861–863 negatron decay and, 868–869 Proto-oncogenes, 834 Proximal coordinate systems, 176–178 Proximal position, 74–75 Pseudo-plastic fluids, 188 Psychosocial adjustment, 220, 223 PUBMED, 268 Pulmonary artery, 95, 96 Pulmonary circulation, 95, 96 Pulmonary semilunar valve, 96 INDEX Pulmonary valves, 99 Pulmonary vein, 95 Pulsed wave (PW) Doppler, 938–939 Pulse-echo waveforms, 911, 912 Pulse height analyzers, 877–878 Pulse oximeters, 532 Pulse oximetry, 532–534 Pulse repetition period (PRPs), 909 Pulse-step inputs, saccadic eye movement and, 735 Pulse timing sequences, 967 Purcell, Edward, 940 Pure rotational system, 895 Purine bases, 77 Pyrimidine bases, 77 Pyrolytic carbon, 306–307 Q Qualitative modeling, 694 Quality assurance, 243 Quality of life euthanasia and, 45–49 research ethics and, 53 Quantitative modeling, 694 Quantization, biological signal acquisition and, 561 Quantum dots, 1014–1015 Quantum numbers, 863 Quasi-ballistic light, 1035–1036 Quick release experiments, 743–744 Quinlan, Karen Ann, 44–45 R RADAR, 909 Radial keratectomy, 999, 1003 Radians, 469, 596 Radiation imaging, 857–904 See also medical imaging atomic structure and emissions in, 863–871 basic concepts in, 859–861 elementary particles in, 861–863 emission imaging systems, 859–876 gamma cameras in, 879–881 instrumentation for, 876–882 positron, 881–882 radiation measurement units and, 874–876 radioactive decay and, 871–874 radiographic systems for, 882–902 scintillation detectors in, 877–879 Radiation reactance, 921 Radiative transfer theory, 1008–1009 Radioactive decay, 871–874 Radioactive tracers, 859 Radioactive wastes, 876 Radioactivity, 860, 863 half-life and, 872–874 Radiographic imaging systems, 882–902 basic concepts in, 882–993 Radiometer system, 998 Radionuclides, 866 choosing, 874 commonly used, 875 electron capture and, 870–871 isomeric transition and, 871 positron imaging and, 881–882 Radiopharmaceuticals, 874 Radiotherapy, 893 Radium, 860 RAD (radiation-absorbed dose), 874–875, 876 Raman scattering, 1008–1011 Raman spectroscopy, 1010–1011 surface-enhanced, 1015 Random access memory (RAM), 486 Random biosignals, 555–556 signal averaging and, 600–601 Rayleigh refractometers, 1002–1006 Read only memory (ROM), 486 Reagents, indicator-mediated fiber optic sensors and, 542–543 Reasonable foresight, 67 Receptors cell communication and, 355–358 cell modeling and, 834–835 cellular functions and, 360 GLUT, 835 in homeostasis, 120–121 tissue engineering and, 328 tyrosine kinase, 845 Recirculation effects, 722 dye dilution model and, 722 Recovery from errors, 236–238 Reed–Frost model, 715–717 Reference electrodes, 534–535 Reference frame notation, 948 Reflection diffuse, 1008 specular, 1008 specular, in vision, 932 ultrasound and, 910–911, 913–918, 914–917 Reflex arcs, 108, 109 Reflexes, 108, 109 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1111 1111 INDEX Refraction optical biosensors and, 539–540 ultrasound and, 917 Refrigeration, 11 Rehabilitation Act of 1973, 214, 241 Rehabilitation Act of 1986, 215 Rehabilitation engineering, 211–254 activities in, 217–218 adaptability and flexibility in, 238 age appropriateness and, 238–239 analysis in, 227–228 anatomical control sites in, 232, 234–235 career opportunities in, 239–241 centers of excellence in, 214 certification in, 241–242 decision making in, 228–229 definition of, 212 display suitability in, 236 engineering principles in, 229–231 ergonomic principles in, 231–239 evaluation in, 228 history of, 212–217 human component in, 218–224 implementation in, 229 information sources for, 217 outlook for, 241–243 principles of, 227–239 proper positioning in, 231–232, 233 recovery from errors in, 236–238 reimbursements for, 215 shortages of professionals in, 215 simplicity and intuitive operation in, 235–236 synthesis in, 228 Rehabilitation Engineering and Assistive Technology Society of North America, 215 Rehabilitation Engineering Centers research grants, 216–217 Rehabilitation Engineering Centers (RECs), 214 Rehabilitation Engineering Society of North America (RESNA), 215 certification through, 241–242, 251–252 Rehabilitation Research and Training Centers, 214, 217 Rehabilitation technology See assistive technology Rehab Management, 240 Reid, J., 911 Reid, Lola M., 313–401 Rejection reactions, 321–322 b-islet cells and, 324, 325 immunogenicity and, 288–290 tissue engineering and, 388 Relaxation constants, 940, 941 Relaxation times, 952–953 Remi, Enrico, 868 remodeling, tissue, 283 wound healing and, 346 REMs (roentgen equivalent man), 875 Repolarization, 97 Reporters, 805–806 Reporting requirements medical device, 69–70 Reproducibility, 507 Reproductive system, 94, 363 Research biomedical engineering, 24 federal programs in rehabilitation engineering, 215–216 human experimentation, 49–70 Human Genome Project, 15, 88, 800, 803 nontherapeutic, 52 protocols for, 55 rehabilitation engineering, 215–216 therapeutic, 52 Research and Demonstration program, 214 Residual volume (RV), 102, 104 Resistance, 415–425 in cell membranes, 654 equivalent, 419, 420 in parallel, 420–422 power and, 417–419 resistors and, 415–417 in series, 419–420 in strain gauges, 521 thermistors and, 525–526 The´venin’s theorem and, 436–439 voltage and current divider rules and, 422–425 Resistivity, 416 Resistors, 415–417 current divider rule and, 423–425 in parallel, 420–422 passive circuit elements in the phasor domain and, 470–472 in series, 419–422 voltage divider rule and, 423 RESNA See Rehabilitation Engineering Society of North America (RESNA) Resolution analog-to-digital converter, 561 computerized tomography, 891, 894 sensor, 507 spatial, 891, 894 Resonance surface plasmon resonance sensors and, 544–545 Respiration capacitive displacement transducer measurement of, 522 external, 105 internal, 105–106 metabolic pathway modeling and, 835 Respirators definition of death and, 43–45 Drinker, 11 euthanasia and, 45–49 Respiratory disorders expiratory volume and, 104 in preterm infants, 50–51 Respiratory system, 94–101, 101–106, 363 blood in, 367 Respiratory zone, 101–102 Respirometers, 383, 384 Response time, sensor, 507 Resting heart rate, 97 Resting potentials, 641–642 of membrane permeable to one ion, 644–645 Reswick, James, 212 Retinal periphery, 724–725 Reynold’s transport theorem, 191 RGB (red, green, blue) system, 562–563 Rheology, 189 Ribosomal RNA (ribonucleic acid), 88 Ribosomes, 85 in translation, 804 Richardson, L.F., 908–909 Right atrium, 96 Right-hand rule, 942 Right ventricle, 96 Ring artifacts, 895 Rippling effects, 605 Rise time, 785 rms value, 468 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1112 1112 RNA polymerase, 803 RNA (ribonucleic acid), 77 genes, 801 genomics and, 800–804 messenger, 88, 803 modeling production of, 845–846 ribosomal, 88 sequence alignment, 815–819 transfer, 88, 803 Robinson, D.A., 735, 763–764 Roentgen, W K., 10, 405, 858 roentgens, 874–875 Roman Catholic Church, 6–7 Roman views of disease, 4–6 Root aortic pressure, 202 Roots, MATLAB, 1055–1059 Rotating-anode tubes, 898 Rotating frame approach, 948–949 Rotation, mass moment of inertia and, 147–150 Rough endoplasmic reticulum, 85 Rouleaux, 190 Row-column scanning, 234–235 Row vectors, 1046 Runge–Kutta approximation, 838 Russell’s traction rigs, 143–144 Rutherford, Ernest, 860–861 S Saccades, 723 characteristics of, 725–728 duration and magnitude of, 727, 728 generation of, 725 recording, 735–738 Saccadic eye movement, 723–771 active-state tension generator in, 737–738, 740–741 elasticity in, 741–742 force–velocity relationship in, 745–751 linear homeomorphic models of, 757–771 linear muscle model for, 751–757 oculumotor muscle model of, 738–751 passive elasticity in, 738–739 saccade controller in, 735–738 system identification and, 772 Weistheimer model of, 728–734 Sacral/coccygeal curve, 112 INDEX Sacrum, 112 Saddle joints, 113, 114 Safe Medical Devices Act of 1990, 69–70 Safety issues assistive technology and, 230 biomaterials and, 296–301 electric current and, 417–419 electronic equipment and, 20–21 tissue engineering and, 319 Saggital planes, 74, 76 kinematics of, 183–186 Salt bridges, 534–535 Sampled signals, 582 Sampling for analog-to-digital converters, 484–485 biological signal acquisition and, 560–561 computer speeds and, 486 Sanctorius, Sanger Institute, 815 Sanger sequencing, 805–806 Santorio, Santorio, 130 Sapphire, 1029 Sarcolemma, 117 Sarcomeres, 117, 118 distributed muscle model and, 167–169 Sarcoplasm, 117 Sarcoplasmic reticulum, 117 SARS, 820 Satomura, S., 911 Scaffolds, tissue, 294–296 musculoskeletal repair and, 302–303 Scalar products, 134 Scalers, 878–879 Scaling, 382–386 challenges in, 315–317 concepts in, 382 design challenges in, 382 fluid flow and, 385–386 linear systems and, 585–587 mass transfer time scales and, 382–384 medical imaging and, 908 uniformity and, 385–386 Scan conversion, 937–938 Scanning electron microscopes (SEM) biomaterials testing and, 297 Scanning gantries, 885, 894–896 Scan plane, 936 Scattering elastic, 1008 inelastic, 1008, 1009–1011 of light, 983–985 measuring, 994–997 Raman, 1008–1011 transducers and, 931–932 ultrasonic, 931–932 Schleiden, Matthias Jakob, 76–77 Schools, rehabilitation engineers in, 240 Schwann, Theodor, 76–77 Schwann cells, 107, 278 Science, professions vs., 25 Scientific soundness, 63–64 Scintillation detectors, 877–879, 898 Score functions, 817, 819 Secondary mass spectroscopy (SIMS), 297 Second-class levers, 115 Sector arrays, 929 Segment angles, 176–178 Segment mass, 178–182 Selective interference, 879 Self-assembly, peptide, 279 Self-organizing feature maps networks, 618 Self-passivation, 286 Self-testing, patient, 506 Semiconductor strain gauges, 519 Semilunar valves, 99 Senescence, stem cell, 334, 340 See also apoptosis Sensitivity, sensor, 507 Sensitization, 299 Sensors, 407, 505–548 airflow transducers, 524 bioanalytical, 536–539 in biological signal acquisition, 557–558 biopotential measurements by, 508–513 blood gases and, 527–536 carbon dioxide, 535–536 classification of, 507, 508 displacement transducers, 513–524 ECG electrodes, 510–511 EEG electrodes, 512 electrolyte/electrode interface in, 508–510 EMG electrodes, 511 enzyme-based, 536–538 immunoassay, 543–544 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1113 1113 INDEX indicator-mediated fiber optic, 542–543 microbial, 538–539 microelectrodes, 512–513 operating range of, 507 optical, 539–545 oxygen, 528–534 packaging of, 507–508 pH, 527–528, 534–535 physical measurements with, 513–527 pO2, 529–531 probes, 1031–1033 reproducibility of, 507 resolution of, 507 response time of, 507 sensitivity of, 507 surface plasmon resonance, 544–545 temperature measurement with, 524–527 Sensory neurons, 106 Septum, 96 Sequence alignment, 815–819 Series elastic elements, 743–744 Serine, 92 SERS See surface-enhanced Raman spectroscopy (SERS) Seth, Settling time, 785 Shape memory alloys, 268 Shear stress of bone, 155 cell–cell contact and, 358–359 of fluids, 187–190 Shear thickening, 188 Shear thinning, 188 Shell model, 864 Shift operator, 582 Short circuits, 415 Short-time Fourier transform, 605–607 Shotgun sequencing, 806–807 Shoulder joint replacements, number of, 256 Sialoprotein, 290, 291 Siemens, 654 Signal acquisition, 557–562 analog-to-digital conversion and, 558–562 sensors, amplifiers, and analog filters in, 557–558 Signal averaging, 597–604 Signal-to-noise (S/N) ratio, 485 Signal transducers and activators of transcription (STATs), 358 Signal transduction responses, 328 modeling, 840–845 Silent polymorphisms, 811–812 Silicone rubber, 263 heart valves, 306–307 Silk, 274 Silly Putty, 188 Silver as biomaterial, 263, 264 in mercury amalgams, 276 Silver/silver chloride electrodes (Ag/AgCl), 510–511 Simple feedback circuits, 108 Simple sequence repeats (SSRs), 812 Simplicity and intuitive operation, 235–236 Simulation See also modeling; SIMULINK cellular modeling and, 834 rehabilitation engineering and, 229 solutions in, 697 SIMULINK, 1048, 1072–1083 Fcn block in, 1082 fixed- and variable-step solvers in, 1075–1077 GK and GNa equations in, 673 interaction between adjacent neurons in, 681–683 Kermack–McKendrick continuous time model in, 711–715 Library Browser, 1072, 1073 linear homeomorphic model in, 766–771 Math Function block in, 1082 modeling in, 836–837 model of viscoelastic properties, 160, 161 printing in, 1077 Reed–Frost model in, 716–717 running simulations in, 1074–1077 saving models in, 1077 scope block in, 1074 starting, 1072 Switch block in, 1083 threshold conditions in, 1082–1083 time dependence equations for membrane potentials in, 677–679 Simultaneous equations matrices and, 1047–1048 Single nucleotide polymorphisms (SNPs), 811–812 Single photon emission computed tomography (SPECT), 1033 Sinoatrial node, 95, 97 Sinusoidal analysis, system identification and, 773–781 Sinusoids electromagnetic waves, 979–982 phasors and, 469 rms value of, 468 time-varying signals and, 468–474 Skalak, Richard, 320–321 Skeletal muscle tissue, 93 characteristics of, 116 fast, 119 hierarchical structure of, 280 slow, 119 Skeletal system, 94–101, 111–113 Skin biomaterials for, 303–305 grafts, 303, 322–323 maturational lineage and, 336 regeneration of, 303–305 structure of, 303–304 Slab gel systems, 806 Slice plane location, 956–959 Slip rings, high-voltage, 896 SLT See sonoluminescent tomography (SLT) Smallpox, 708–717 Smith–Waterman algorithm, 818, 820 Smooth endoplasmic reticulum, 85 Smooth muscle tissue, 93 characteristics of, 116 Smooth pursuit eye movements, 723 Snell’s law fiber optics and, 1027 light propagation and, 985 optical fibers and, 539–541 ultrasound and, 916–918, 918 SNP Corsortium, 811 Sodium cellular concentrations of, 79–80 conductance waveform, 673–675 Soft computing, 612 Soldner, R., 912 Solid freeform fabrication, 296 Solid-state microprobes, 512–513 Soluble growth factors, 355–358 Soluble signals, 327 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1114 1114 Solutes concentrations of, 701 transfer of between two compartments, 698–701 transfer of by fluid flow, 718–720 Solvent casting, 295 Somatic nervous system, 106–107 Somer, J.C., 913 SONAR, 909 Sonoluminescence, 1038–1039 Sonoluminescent tomography (SLT), 1039 Soundness, scientific, 63–64 Sources, electrical, 414–415 dead, 437 superposition and, 432–436 Space charge neutrality, 646, 647 Goldman equation and, 650–651 ion pumps and, 651–653, 652–653 Space clamps, 665–666 Spare parts surgery, 13, 54 ethics and, 32 Spatial resolution, 891, 894 Spec sheets, 362, 364 estimating tissue function from, 365–369 SPECT See single photon emission computed tomography (SPECT) Specular reflection, 1008 Specular scattering, 931 Spherical waves, 913 Sphygmomanometry, 99–100 Spina bifida, 233 Spinal cavity, 75 Spine metallic devices for, 267 spinal nerves, 106 Spin echo method, 955–956 Spin gyromagnetic ratio, 946 Spin lattice recovery time, 950 Spin quantum number, 863 Spin-spin relaxation time, 952 Spin states, 944–947 Spirometry, 103–104 Spongy bone, 112 Square matrix, 1047 Squid giant axons Goldman equation and, 648–651 Hodgkin–Huxley model and, 664–679 time dependence equations for membrane potentials, 675–679 INDEX SQUID magnetometers, 551 Stainless steel as biomaterial, 263, 264 elastic modulus of, 155–156 mechanical properties of, 153 self-passivating, 286 Start codons, 90–91, 822–823 Static equilibrium, 143–147 Statistical Essays (Hales), 130 Steady-state response bioinstrumentation and, 469 Stefan–Boltzmann constant, 998 Stem cells, 331–355 aging of, 340 biomaterials and, 257 bone marrow transplants and, 321–322 cell differentiation and, 346–355 determined, 331 ethics of research in, 35–36 evidence for existence of, 332 ex vivo growth of, 339 heart valves and, 307 isolation of, 339–340 maturational lineage and, 333–338 mesenchymal, 277 niche hypothesis and, 331–333 pluripotent, 331 proliferative behavior models for, 339 rarity of, 340 roles of, 333 therapies, clinical trials for, 326 tissue dynamics and, 340–346 tissue engineering and, 339–340 totipotent, 331 Stents materials for, 268–269 number of used, 257 Step-index fibers, 1028 Stereolithography, 296 sterilization, 508 Steroids receptors for, 834 transfer of solutes by fluid flow and, 718–720 Stewart, Alice, 912 Stiffness See elastic modulus Stiff ordinary differential equations, 838 Stimulatory interactions, 849 Stochastic models, 339, 696 Stochastic signals, 555–556 Stokes bands, 1010 Stokes vector, 982 Stop-band, 474 Stop codons, 90–91, 822–823 Strain gauges, 519–522 Stratum corneum, 303–304 Stress relaxation, 160, 161, 162, 165 Stress shielding, 268 Stress–strain curves biomaterials testing and, 259–260 of bone, 151–159, 157 of fluids, 187–190 of tendons, 165–166 Stroma, 322–323 stem cells and, 333 Strontium 85, 874 Structural genes, 801 Subdermal needle electrodes, 512 Substrate concentration, 838–839 Sulci, 108–109 Sulfanilamide, 10–11 Sulzer, Johann, 632 Summation See backprojection Superior colliculus, 724 Superior oblique, 723 Superior position, 74–75 Superior rectus, 723 Superior vena cava, 96, 100 Supernodes, 430–432 Superposition, 432–436 linear systems and, 585–587 phasor domain and, 472 Supersequences, 819–820 Supervised algorithms, 827 Supervised learning, 618 Surface chemistry modifications, 290–292 Surface-enhanced Raman spectroscopy (SERS), 1015 Surface plasmon resonance, 541–542 sensors based on, 544–545 Surface tension, 102 Surface topography, 292–293 Surfactants, 102 Surgery aseptic, 256 early development of, 11–12 ethics and, 32 laser, 16 organ/tissue deficiencies and, 319–320 spare parts, 13, 32, 54 Swammerdam, Jan, 130 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1115 1115 INDEX Swan-Ganz thermodilution, 526, 527 Sympathetic nervous system, 106–107 Symptomatic period, 709 Synapses, 107 Synaptic vesicles, 107 Synergists, 114 Syngeneic transplants, 319 Synonymous polymorphisms, 811–812 Synovial cavities, 75 Synovial joints, 112–113, 114 System automation, 315 Systemic circulation, 95, 96 arteries, 96 Systemic factors, 327 System identification, 771–787 active-state tension and, 759–760 classical, 773–781 definition of, 772 of linear first-order systems, 781–784 of linear second-order systems, 784–787 in MATLAB, 781 sinusoidal analysis in, 773–781 System transfer function, 588–589, 589 Systolic pressure, 99–100 Szabo, Thomas, 905–975 Szeto, Andrew, 211–254 T Tachycardia, 615–616 Taylor series, in Kermack–McKendrick continuous time model, 710 TeamRehab, 240 Technological entrepreneurship, 23 Technology See also assistive technology; bioinstrumentation after WWII, 12–13 definition of death and, 41–45 development of medical, 404–405 electrical safety and, 20–21 ethics and, 32–33 expansion of medical, 15 performance inspections and, 20–21 potential of, 15, 17 Technology-Related Assistance Act of 1988, 215 Telecommuting, 242 Telemedicine, 406–407 Telomerase, 332 stem cell aging and, 340 Telomeres, 340, 341 Temperature Arrhenius–Henriques model for quantitative analysis and, 1023–1025 biomedical optics and, 998–1000 effect of vaporization and ablation, 1025–1026 lasers and, 1015–1016, 1017–1018 light-induced heating and, 999 measurement of body, 524–527 monitoring, 998–999 rehabilitation engineering and, 229–230 Temporal lobes, 109 Tendons, biomechanics of, 163, 165–166 Tensile testing, 258–260 Terminal illness, ethics and, 45–49 Tetracalcium phosphate, 269 Thalamus, 109–110 Thales of Miletus, 629 Thalidomide, 214 Therapeutic research, 52 Thermistors, 524–526 Thermodilution, 526, 527 Thermographic system, 998 Thermometers, 524–525 noncontact, 525, 526 Thermoplastic polymers, 272, 273 Thermosetting polymers, 272–273 The´venin’s theorem, 436–439 equivalent circuit for three ions and, 656–657 equivalent circuits and, 419 neuron capacitance and, 658–659 Thigh anatomical coordinate system, 173–176 Thigh technical coordinate system, 174–176 Third-class levers, 115–116 Thompson, J.J., 860 Thompson, William, Lord Kelvin, 162 Thoracic cavity, 75 Thoracic curve, 112 Thoth, 3-D printing, 296 Three-dimensional direction cosines, 137–138, 139 Three-neuron circuits, 108 Threshold potentials, 664–666 Thymine, 77 Tidal volume (TV), 102 Time course experiments, 807, 809 Time dependence equations for membrane potentials, 675–679 Time domain linear systems in, 587–588 system identification in, 781–784 Time gain compensation (TGC) amplifiers, 937–938 Time shifting, 576–577 Time-varying signals, 468–474 passive circuit elements in the phasor domain and, 470–472 phasors and, 469 Tissue characterization, 911 Tissue engineering, 17, 313–401 biological considerations in, 331–360 biomaterials and, 257, 381 cell differentiation and, 346–355 cellular communication and, 355–360 cellular therapies and, 318–319 challenges in, 315–317, 374 clinical considerations in, 330–331 definition of, 314 ECM and, 328 epithelial–mesenchymal relationship and, 326–327 functional, 391–392 future directions in, 390–393 grafts/extracorporeal bioartificial organs and, 318–319 heart valves and, 307 history of, 320–321 human cells/grafts as therapeutic agents in, 319–326 mass transfer and, 369–371, 382–384 microenvironments in, 371–381 natural tissue construction, 276–277 orders of magnitude and, 328–330 physical considerations in, 360–381 product implementation in, 386–390 scaling up in, 382–386 soluble signals and, 327 spec sheets and, 365–369 stem cells in, 326, 331–340 tissue dynamics and, 340–346 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1116 1116 Tissue engineering, (continued ) tissue functional subunits in, 360–365 tissue mechanisms and, 326–330 Tissue Engineering, 321 Tissues, 92–93 acoustic properties of, 909–910 definition of, 92 dynamics of, 340–346 formation of, 343 functional subunits of, 360–365 genesis of, 344–345 histogenesis of, 344 laser damage to, 1017–1018 light propagation in, 985–997 optical properties of, 996 repair of, 343, 345–346 turnover rates, 344 types of, 92–93 Tissue typing, 289 Titanic, 908 Titanium alloys as biomaterial, 263, 264 heart valves, 307 mechanical properties of, 153 Tomography, 882–902 basic concepts in, 882–893 optical-coherence, 1037 optical tomographic imaging, 1035–1037 photoacoustic, 1038 plane, 884 positron emission, 881–882 sonoluminescent, 1039 technology of, 893–902 ultrasound-modulated optical, 1037–1038 Tone bursts, 949–950 Tonicity, 80 Top down clustering, 827 Total hip replacments See hip replacements Total lung capacity (TLC), 102, 103–104 Total specific intensity, 991–992 Totipotent stem cells, 331 Toughness, 261–262 Transcription, DNA, 88–89, 90–91, 802–804 bionetworks and, 846, 847 Transducers, 912, 918–930 See also sensors airflow, 524 INDEX aperture shapes in, 933–935 arrays of, 913, 927–930 in assistive technology, 233 capacitive displacement, 521–522 diffraction and, 933–936 displacement, 513–524 electrical impedance in, 919–922 electromagnetic flow, 514–519 frame rates and, 930 frequency response of, 922–927 indicator-mediated fiber optic sensors and, 542–543 linear variable differential transformers, 513–514, 515 piezoelectric, 522–524 placement of, 911 strain gauges, 519–522 Transesophageal transducers, 930 Transfer function, 587 analog filter output and, 591–592 digital filter design and, 596 in system identification, 774–775 Transferrin, 347 Transfer RNA (ribonucleic acid), 88, 803 in replication, 89–90 in translation, 90–91 Transformation matrices, Euler angle, 138, 140–143 Transient biosignals, 555 Transit amplifying cells, 336 Transition distance, 934 Transition probabilities, 821–822 Translation, DNA, 804 bionetworks and, 846, 847 Transmembrane ion gradients, 80 Transmission factors, 915–916 Transmutation, 866–867 Transplants allogeneic, 319, 321–322, 388 autologous, 319, 321, 324–326, 390 bone marrow, 319, 321–322 knees and, 324–326 rejection of, 388 types of, 319 Transport theorem optics and, 985, 988–994, 991–992 Reynold’s, 191 scattering and absorbing media and, 991–992 Transversal magnetization relaxation constant, 940 Transverse arterial compliance, 193 Transverse load, of bone, 156 Transverse planes, 74, 76 Transverse tubules, 117 Traverse and index system, 894–895 Tricalcium phosphate, 288 Tricuspid valve, 96, 99 Trigonometric Fourier series, 562–567 in MATLAB, 565–567 Triphination, 2–3 Triple primed coordinate systems, 176–178 Tritium, 863 Trochlea, 723 Tubulin, 87 Tumor growth factors (TGFs), 327 Tumors, stem cells and, 333 T waves, 98–99 Two-flux model, 992 Two-neuron circuits, 108 Two New Sciences (Galileo), 129 Tympanic cavity, 75 Tyrosine kinases, 834 receptors, 845 U UHMWPE, mechanical properties of, 153 Ultimate tensile strength (UTS), 260 Ultrasound imaging, 908–940 absorption and, 932–933 applications of, 1033–1034 blood pressure measurement with, 100 compared with other imaging techniques, 971 diffraction and, 933–936 electrical impedance in, 919–922 focal depth to aperture ratio in, 971 Fourier transforms and, 907–908 frequency response in, 922–927 modes in, 938–940 oblique waves at liquid–liquid boundaries in, 916–918 origins of, 908–913 piezoelectric transducers and, 523–524 scattering and, 931–932 systems for, 936–938 three-dimensional, 939–940 transducers in, 918–930 wave propagation, reflection, refraction in, 913–918 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1117 1117 INDEX Ultrasound-modulated optical tomography, 1037–1038 Unified electromagnetic theory, 443 Uniformity, scaling up and, 385–386 United Cerebral Palsy Association, 240 Unit-sample of impulse sequence, 560 Unit-step sequence, 560 Universal access and design, 242 Universal donors, 319 Universal gas constant, 1018–1019 Unprimed coordinate systems, 138, 139 gait analysis and, 176–178 Unsupervised algorithms, 827 Unsupervised learning, 618 Upper extremities, 75 Urinary system, 94, 363 Urist, M.R., 275 Uropods, 351 U.S Department of Education, 215–216 Utilitarianism, 34, 69–70 V Vaccines, 289–290 Validated practice, 65 van der Waals bonding, 291 Vaporization, 1025 V-Cell, 836–837 Vector equations Euler’s, 150–151 of motion, 150–151 Newton’s, 150 static equilibrium and, 143–147 Vector mathematics, 131–137 adding in, 133 angle of orientation in, 132 cross products in, 135 direction cosines in, 133 magnitude in, 132 in MATLAB, 135–137 moment of force in, 134–135 multiplication in, 134 norm in, 132 subtraction in, 133 Vectors column, 1045–1046 Jones, 982 magnetic resonance imaging and, 942 in MATLAB, 1052–1053 row, 1046 Stokes, 982 Veins, 95 Venae cavae, 96, 100 Venter, Craig, 806 Ventilators high frequency jet, 106 negative pressure, 106 positive pressure, 106 Ventral body cavity, 75 Ventral position, 74, 75 Ventricular elastance, 194–200 ejection effect and, 202–205 MATLAB for, 198–200 pressure–volume work loops and, 205–207 Ventricular fibrillation, 418, 557 Ventricular pressure, 201–203 Ventricular repolarization, 98–99 Ventriculoscopes, 1031 Venules, 96, 100 Vergeance eye movements, 723–724 Vertebrae, 112 Vertebral column, 112 Vesalius, Andreas, 130 Vesicles, 78, 84 Vestibular ocular movements, 723 Veterans’ Administration (VA), 21, 213–214 Bulletin of Prosthetic Research, 217 Villi, 335 Virchow, Rudolf, 77 Viscoelastic properties, 159–163 Kelvin body model of, 159, 162–163 Maxwell model of, 159, 160–161, 162 Simulink model of, 160, 161 Voight model of, 159, 162 Viscosity, 187–190 eyeball, 758–759 force–velocity relationship and, 747–751 linear muscle model and, 751–757 Vision See also saccadic eye movement RGB system and, 562–563 specular reflection in, 932 Visitations, disease as, 2–3 Vital capacity (VC), 102, 104 Voice-recognition systems, 242 Voight, Woldemar, 162 Voight viscoelastic model, 159, 162, 163, 164 Volta, Allesandro, 629, 633–637 Voltage, 411–413 capacitors and, 443–445 clamp, 668–670 constant, 412 divider rule, 423, 454 drop in across inductors, 440 drop in across resistors, 415 Kirchhoff ’s law of, 412–413 operational amplifiers and, 455, 467–468 passive circuit elements in the phasor domain and, 470–472 sinusoidal sources of, 468–474 The´venin’s theorem and, 436–439 time-varying, 412 Voltage clamp experiment, 664–666 GNa and GK equations in, 672–675 Volts, 412 Volume rendering, 940 Voxels, 885–886, 956 W Waveforms aortic pressure, 572, 573 blood pressure and, 552–553 current, 445–446 MRI detected response, 953–956 potassium conductance, 673 pulse-echo, 911 sodium conductance, 673–675 wavelet analysis and, 605, 607–611 Waveguides, 1026–1033 Wavelet transform, 605, 607–611 Wave theory, 986–988 Weber, Eduard, 131 Weber, Ernst, 131 Weistheimer model of saccadic eye movement, 728–734, 738 Welch averaging method, 601–602 Westerhof viscoelastic model, 163 Wet etching, 293 Wet synthesis methods, 269–271 Wheelchairs, 219 Wheelchair Standards Committee, 243 White matter, 109 Whole brain death, 43–44 Wild, J.J., 911 Wireless technology, 243 Withdrawal reflexes, 108 Work definition of, 134 vector mathematics and, 134 Enderle / Introduction to Biomedical Engineering 2nd ed Final Proof 2.2.2005 7:17pm page 1118 1118 World Medical Association, 37 informed consent guidelines, 53–59 World War II technology, 12–13 assistive technology and, 213–214 ultrasound, 908–909 Worst-case design, 229 Wound healing, 282–283 biomaterial degradation and, 288 sequence of events in, 345–346 Wyman, A., 743 INDEX X Xenogeneic transplants, 319 Xenon 133, 871 Xenon detectors, 898 x-ray photoelectron spectroscopy (XPS), 297 x-rays See also radiation imaging advantages and disadvantages of, 884 attenuation of, 886–888 basic concepts of, 859–861, 882–893 discovery of, 10, 405, 858 emission of, 858–859 in micro-CT, 297–298 pregnancy and, 912 Y Yoshida, T., 911 Young, Thomas, 130 Z Zirconia, 263 Z lines, 117, 118 z transform, 579–583 properties of, 583–584 ... 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...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. .. 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 Biomedical