BIOMEDICAL INFORMATION TECHNOLOGY pdf

BIOMEDICAL
INFORMATION
TECHNOLOGY
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BIOMEDICAL
INFORMATION
TECHNOLOGY
EDI TED BY
DAVID DAGAN FENG
PROFESSOR, SCHOOL OF INFORMATION TECHNOLOGIES
UNIVERSITY OF SYDNEY
and
CHAIR-PROFESSOR OF INFORMATION TECHNOLOGY
HONG KONG POLYTECHNIC UNIVERSITY
AMSTERDAM • BOSTON • HEIDELBERG • LONDON
NEW YORK • OXFORD • PARIS • SAN DIEGO
SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
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Except Chapter 15, ‘‘Integrated Multimedia Patient Record Systems, ’’ which is
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Contents
Acknowledgments xi
About the Editor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Contributors xv
Introduction xvii
Section I: Technological Fundamentals
Chapter 1 Medical Imaging Dr. Xiaofeng Zhang, Prof. Nadine Smith, and Prof. Andrew Webb 3
1.1 Introduction 3
1.2 Digital Radiography 4
1.3 Computed Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4 Nuclear Medicine 7
1.5 Ultrasonic Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.6 Magnetic Resonance Imaging . . 15
1.7 Diffuse Optical Imaging . 18
1.8 Biosignals . . 22

1.9 Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
1.10 Exercises 25
1.11 References and Bibliography 27
Chapter 2 Electronic Medical Records Dr. Eugene Y. S. Lim, Prof. Michael Fulham,
and Prof. David Dagan Feng
29
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.2 Medical Data and Patient Records . . 31
2.3 Terminology Standards—Vocabulary and a Clinical Coding System . . . . . . . . . . . . . 34
2.4 Information Exchange Standards 38
2.5 Usability Issues in Electronic Medical Records 38
2.6 User Interface . . 40
2.7 Evaluation 42
2.8 Electronic Medical Records System—A Case Study: A Web-Based Electronic Record for Medical Imaging . . . . 42
2.9 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
2.10 Exercises 45
2.11 References and Bibliography 46
Chapter 3 Image Data Compression and Storage Prof. Hong Ren Wu, Dr. Damian M. Tan,
Dr. Tom Weidong Cai, and Prof. David Dagan Feng
51
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.2 Picture Compression 51
3.3 Compression in the DICOM Standard . . 69
3.4 Data Compression for Dynamic Functional Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
3.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.6 Exercises 78
3.7 References and Bibliography 78
v
Chapter 4 Content-Based Medical Image Retrieval Dr. Tom Weidong Cai, Dr. Jinman Kim,
and Prof. David Dagan Feng

83
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
4.2 Content-Based Medical Image Retrieval by Physical Visual Features 88
4.3 Content-Based Medical Image Retrieval by Geometric Spatial Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
4.4 Content-Based Medical Image Retrieval by Combination of Semantic and Visual Features . . . 100
4.5 Content-Based Medical Image Retrieval by Physiologically Functional Features . . . . . . . . . . . . . . . . . . . . . 107
4.6 Summary 107
4.7 Exercises 107
4.8 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Chapter 5 Data Modeling and Simulation Dr. Alessandra Bertoldo and Prof. Claudio Cobelli 115
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.2 Compartment Models 115
5.3 Model Identification . . . 118
5.4 Model Validation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
5.5 Simulation 127
5.6 Case Study 128
5.7 Quantification of Medical Images 130
5.8 Exercises 135
5.9 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Chapter 6 Techniques for Parametric Imaging Prof. David Dagan Feng, Dr. Lingfeng Wen,
and Dr. Stefan Eberl
137
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
6.2 Parametric Image Estimation Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
6.3 Noninvasive Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.4 Clinical Applications of Parametric Images 152
6.5 Summary 158
6.6 Exercises 159
6.7 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Chapter 7 Data Processing and Analysis Prof. Yue Wang, Prof. Chris Wyatt, Prof. Yu-Ping Wang,

Prof. Matthew T. Freedman, and Prof. Murray Loew
165
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
7.2 Medical Image Enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
7.3 Medical Image Segmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
7.4 Medical Image Feature Extraction 174
7.5 Medical Image Interpretation 177
7.6 Summary 182
7.7 Exercises 183
7.8 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Chapter 8 Data Registration and Fusion Dr. Xiu Ying Wang, Dr. Stefan Eberl,
Prof. Michael Fulham, Dr. Seu Som, and Prof. David Dagan Feng
187
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
8.2 Fundamentals of Biomedical Image Registration and Fusion . . . 188
8.3 Feature-Based Medical Image Registration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
8.4 Intensity-Based Registration . . 195
vi
8.5 Hybrid Registration and Hierarchical Registration 198
8.6 Hardware Registration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
8.7 Assessment of Registration Accuracy . . . . . . . . 201
8.8 Applications of Biomedical Image Registration and Fusion . . 203
8.9 Summary 205
8.10 Exercises . . . 205
8.11 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Chapter 9 Data Visualization and Display Dr. Jinman Kim, Dr. Tom Weidong Cai,
Prof. Michael Fulham, Dr. Stefan Eberl, and Prof. David Dagan Feng
211
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
9.2 Two-Dimensional Visualization Techniques 212

9.3 Three-Dimensional Visualization Techniques 213
9.4 Volume Navigation Interface 215
9.5 Volume Enhancement and Manipulation . . . 216
9.6 Large Data Visualization and Optimization . . . 218
9.7 Dual-Modality Positron Emission Tomography–Computed Tomography Visualization 219
9.8 Data Display Devices 222
9.9 Applications of Biomedical Visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
9.10 Summary 224
9.11 Exercises . . . 224
9.12 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Chapter 10 Data Communication and Network Infrastructure Prof. Doan B. Hoang and
Dr. Andrew J. Simmonds
229
10.1 Introduction . . 229
10.2 Transmission and Communication Technologies 230
10.3 The Internet and World Wide Web 233
10.4 Wireless and Mobile Technologies in M-Health 238
10.5 Sensor Networks for Health Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
10.6 Applications of Wireless Technologies in Telemedicine . . . 245
10.7 Summary 247
10.8 Exercises . . . 247
10.9 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Chapter 11 Data Security and Protection for Medical Images Dr. Eugene Y. S. Lim 249
11.1 Introduction . . 249
11.2 Overview of Cryptographic System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
11.3 Digital Watermarking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
11.4 Medical Image Watermarking . . . . . 252
11.5 Region-Based Reversible Watermarking for Secure Positron Emission Tomography Image Management 254
11.6 Summary 255
11.7 Exercises . . . 255

11.8 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Chapter 12 Biologic Computing Prof. Eric P. Hoffman, Erica Reeves, Dr. Javad Nazarian, Dr. Yetrib Hathout,
Dr. Zuyi Wang, and Josephine Chen
259
12.1 Introduction . . 259
12.2 Overview of Genomic Methods . . . . . . . . 259
12.3 Overview of Proteomic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
12.4 Bioinformatics and Information Infrastructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
vii
12.5 Data Mining and Large-Scale Biologic Databases 270
12.6 Biologic Event-Driven, Time-Driven and Hybrid Simulation Techniques 271
12.7 Summary . 274
12.8 Exercises . . 275
12.9 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Section II: Integrated Applications
Chapter 13 PACS and Medical Imaging Informatics for Filmless Hospitals Prof. Brent J. Liu
and Prof. H. K. Huang
279
13.1 Introduction 279
13.2 PACS Infrastructure . . 280
13.3 PACS Components and Workflow 286
13.4 PACS Controller and Image Archive . . . 291
13.5 Large-Scale PACS Implementation . . . . . . . . . . . . . . 295
13.6 PACS Clinical Experiences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
13.7 Summary 304
13.8 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
13.9 References and Bibliography 305
Chapter 14 KMeX: A Knowledge-Based Digital Library for Retrieving Scenario-Specific
Medical Text Documents
Prof. Wesley W. Chu, Dr. Zhenyu Liu, Dr. Wenlei Mao,

and Dr. Qinghua Zou
307
14.1 Introduction 307
14.2 Extracting Key Concepts From Documents . . 308
14.3 Transforming Similar Queries into Query Templates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
14.4 Topic-Oriented Directory . . 313
14.5 Phrase-Based Vector Space Model for Automatic Document Retrieval 317
14.6 Knowledge-Based Scenario-Specific Query Expansion 325
14.7 The KMeX System Architecture for Retrieving Scenario-Specific Free-Text Documents . . . 338
14.8 Summary 338
14.9 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
14.10 References and Bibliography . . 340
Chapter 15 Integrated Multimedia Patient Record Systems Dr. Ruth E. Dayhoff, Mr. Peter M. Kuzmak,
and Mr. Kevin Meldrum
343
15.1 Introduction 343
15.2 Multimedia Patient Record . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
15.3 Components of the Multimedia Patient Record System Architecture 346
15.4 Electronic Medical Chart Components 348
15.5 Objects Comprising the Multimedia Patient Record . . . 352
15.6 Capturing Multimedia Data with a Clinical Workstation . . 352
15.7 DICOM Image Acquisition . . 352
15.8 Remote Data and Image Viewing Across the Health Care Network 354
15.9 Impact on Patient Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
15.10 Summary . . . 356
15.11 References and Bibliography . . 357
Chapter 16 Computer-Aided Diagnosis Prof. Maryellen L. Giger and Dr. Kenji Suzuki 359
16.1 Introduction 359
16.2 Computer-Aided Diagnosis 359
16.3 Computer-Aided Diagnosis for Cancer Screening 362

viii
16.4 Computer-Aided Diagnosis for Differential Diagnosis . . . . . . . 366
16.5 Intelligent Computer-Aided Diagnosis Workstations: Indices of Similarity and Human/Computer Interfaces 367
16.6 Summary . 370
16.7 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
16.8 References and Bibliography 370
Chapter 17 Clinical Decision Support Systems Dr. Peter Weller, Dr. Abdul Roudsari, and Prof. Ewart Carson 375
17.1 Introduction 375
17.2 Overview of Clinical Decision Support Systems . 376
17.3 Human Diagnostic Reasoning 377
17.4 A Structure for Characterizing Clinical Decision Support Systems . 379
17.5 Decision Support Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
17.6 Decision Support Systems in the Hospital and Other Health Care Settings . 385
17.7 Health Care Education Applications 386
17.8 Verification, Validation, and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
17.9 Summary . 389
17.10 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
17.11 References and Bibliography 390
Chapter 18 Medical Robotics and Computer-Integrated Interventional Medicine Prof. Russell H. Taylor
and Prof. Peter Kazanzides
393
18.1 Introduction 393
18.2 Technology and Techniques 394
18.3 Surgical CAD/CAM . . . . . . . . . . . 403
18.4 Surgical Assistance 406
18.5 Summary . 410
18.6 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
18.7 References and Bibliography 411
Chapter 19 Functional Techniques for Brain Magnetic Resonance Imaging Dr. Sirong Chen,
Dr. Kai-Ming Au Yeung, and Dr. Gladys Goh Lo

417
19.1 Introduction 417
19.2 Diffusion-Weighted Magnetic Resonance Imaging in Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418
19.3 Magnetic Resonance Perfusion Imaging in Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
19.4 Functional Magnetic Resonance Imaging Using BOLD Techniques . . . 424
19.5 Clinical Magnetic Resonance Spectroscopy in Brain 425
19.6 Summary . 428
19.7 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
19.8 References and Bibliography 428
Chapter 20 Molecular Imaging in Cancer Prof. Kristine Glunde, Dr. Catherine A. Foss,
and Prof. Zaver M. Bhujwalla
431
20.1 Introduction 431
20.2 Imaging of Gene Expression . . . 432
20.3 Receptor Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
20.4 Enzyme-Activated Probes 443
20.5 Metabolic Imaging . . 445
20.6 Imaging of Permeability, Perfusion, and Blood Flow 447
20.7 Imaging of the Tumor Microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
20.8 Multimodality Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
20.9 Summary . 452
20.10 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452
20.11 References and Bibliography 453
ix
Chapter 21 Molecular Imaging in Biology and Pharmacology Prof. Sung-Cheng Huang,
Prof. Anna M. Wu, and Prof. Jorge R. Barrio
457
21.1 Introduction and Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
21.2 Considerations for Quantitative Molecular Imaging 460
21.3 Design/Development of Molecular Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

21.4 Molecular Imaging of Beta-Amyloid and Neurofibrillary Tangles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
21.5 Molecular Imaging Using Antibody Probes . . 468
21.6 Some Other Molecular Imaging Applications 470
21.7 Summary and Future Perspectives 471
21.8 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475
21.9 References and Bibliography 475
Chapter 22 From Telemedicine to Ubiquitous M-Health: The Evolution of E-Health Systems
Dr. Dejan Ras
ˇ
kovic
´
, Dr. Aleksandar Milenkovic
´
, Prof. Piet C. De Groen, and Dr. Emil Jovanov 479
22.1 Introduction 479
22.2 Overview of M-Health Systems . . . 480
22.3 M-Health Based on Wireless Body Area Networks . . 484
22.4 Wireless Intelligent Sensors for M-Health 487
22.5 Wireless Mobile Devices for M-Health 491
22.6 Next-Generation M-Health Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492
22.7 Summary 494
22.8 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
22.9 References and Bibliography 495
Chapter 23 Multimedia for Future Health—Smart Medical Home Dr. Jinman Kim, Dr. Zhiyong Wang,
Dr. Tom Weidong Cai, and Prof. David Dagan Feng
497
23.1 Introduction 497
23.2 Multimedia for Human-Computer Interaction 499
23.3 Multimedia Content Management . . 500
23.4 Multimedia Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501

23.5 Smart Medical Home 503
23.6 Telemedicine in the Smart Medical Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
23.7 Sensory Devices and Health Monitoring 505
23.8 Speech Recognition and Conversational Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
23.9 Multimedia Technologies for Patient Education and Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
23.10 Multimedia Operating Theater and Virtual Reality 507
23.11 Summary . . . 508
23.12 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508
23.13 References and Bibliography . . 508
Index 513
x
Acknowledgments
The editor would like to take the opportunity to express his sincerely appreci-
ation to all of the contributors of this book for making it possible to have such a
comprehensive coverage of the most current information in this very dynamic
field, to Dr. Fu for helping with formatting this book, to the support from the
University of Sydney and Hong Kong Polytechnic University, and to the support
from ARC and PolyU/UGC grants.
xi
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About the Editor
(David) Dagan Feng received his
M.E. in Electrical Engineering &
Computing Science (EECS) from
Shanghai Jiao Tong University in
1982, M.Sc. in Biocybernetics and
Ph.D. in Computer Science from
the University of California, Los
Angeles (UCLA) in 1985 and
1988, respectively. After briefly

working as an Assistant Professor
at the University of California,
Riverside, he joined the University
of Sydney at the end of 1988 as a Lecturer, Senior Lecturer,
Reader, Professor, Head of Department of Computer Science,
and the Head of School of Information Technologies. He is
currently an Associate Dean (International IT) of Faculty of
Science at the University of Sydney; Honorary Research Con-
sultant, Royal Prince Alfred Hospital, the largest hospital in
Australia; Chair-Professor of Information Technology, Hong
Kong Polytechnic University; Advisory Professor and Chief
Scientist of Med-X, Shanghai Jiao Tong University; Guest
Professor, Northwestern Polytechnic University, Northeastern
University and Tsinghua University. His research area is
Biomedical & Multimedia Information Technology (BMIT).
He is the Founder and Director the BMIT Research Group. He
has published over 400 scholarly research papers, pioneered
several new research directions, made a number of landmark
contributions in his field with significant scientific impact and
social benefit, and received the Crump Prize for Excellence in
Medical Engineering. More importantly, however, is that many
of his research results have been translated into solutions for
real-life problems and have made tremendous improvements
to the quality of life for those involved. He is a Fellow of the
Australian Academy of Technological Sciences and Engineer-
ing, ACS, HKIE, IEE, and IEEE. Professor Feng is a Special
Area Editor of IEEE Transactions on Information Technology
in Biomedicine, Editorial Board Advisor or member for The
Visual Computer (International Journal of Computer Graphics),
Biomedical Signal Processing and Control, Control Engineering

Practice, Computer Methods and Programs in Biomedic ine, The
International Journal of Image and Graphics (IJIG), and is the
current Chairman of IFAC-TC-BIOMED.
xiii
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Contributors
Professor Jorge R. Barrio, Ph.D.
Department of Molecular and Medical
Pharmacology,
David Geffen School of Medicine,
University of California, Los Angeles (UCLA)
Dr. Alessandra Bertoldo, Ph.D.
Department of Information Engineering,
University of Padova
Professor Zaver M. Bhujwalla, Ph.D.
Director of the JHU In Vivo Cellular and
Molecular Imaging Center,
Director of the Cancer Imaging Resource,
Departments of Radiology and Oncology,
The Johns Hopkins University School of Medicine
Dr. Tom Weidong Cai, Ph.D.
Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Professor Ewart Carson, D.Sc., Ph.D, CEng,
FIET, FIEEE, FAIMBE, FIAMBE
Professor of Systems Science,
Centre for Health Informatics,
City University, London, UK

Josephine Chen
Research Center for Genetic Medicine,
Children’s National Medical Center
Dr. Sirong Chen, Ph.D.
Department of Diagnostic Radiology,
Hong Kong Sanatorium & Hospital, and
Honorary Associate,
Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Professor Wesley W. Chu, Ph.D., FIEEE
Distinguished Professor,
Computer Science Department,
University of California, Los Angeles (UCLA)
Professor Claudio Cobelli, Ph.D., FIEEE
Department of Information Engineering,
University of Padova
Dr. Ruth E. Dayhoff, M.D.
Director, VistA Imaging System Project,
Health Provider Systems, VA Office of Information,
Los Angeles (UCLA)
U.S. Department of Veterans Affairs (VA)
Professor Piet C. De Groen, M.D.
Mayo Clinic
Dr. Stefan Eberl, Ph.D.
Principal Scientist, Department of PET and
Nuclear Medicine,
Royal Prince Alfred Hospital, and
Adjunct Associate Professor,

Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Professor David Dagan Feng, Ph.D., FACS,
FATSE, FHKIE, FIEE, FIEEE
Director, Biomedical & Multimedia
Information Technology (BMIT)
Research Group,
Professor, School of Information Technologies,
University of Sydney,
Honorary Research Consultant,
Royal Prince Alfred Hospital, Sydney, and
Chair-Professor of Information Technology,
Centre for Multimedia Signal Processing,
Department of Electronic & Information
Engineering,
Hong Kong Polytechnic University
Dr. Catherine A. Foss, Ph.D.
Departments of Radiology and Oncology,
The Johns Hopkins University School of Medicine
Professor Matthew T. Freedman, Ph.D.
Department of Oncology and Lombardi
Cancer Center,
Georgetown University
Professor Michael Fulham, M.D.
Director, Department of PET and Nuclear
Medicine,
Royal Prince Alfred Hospital, Sydney,
Adjunct Professor,

Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney, and
Clinical Professor,
Faculty of Medicine,
University of Sydney
Professor Maryellen L. Giger, Ph.D., SMIEEE,
FAAPM, FAIMBE
Professor of Radiology, the Committee on
Medical Physics, and College,
Chair, Committee on Medical Physics
Vice-Chair for Basic Science Research, and
Section Chief, Radiological Sciences,
Department of Radiology,
University of Chicago
Professor Kristine Glunde, Ph.D.
Departments of Radiology and Oncology,
The Johns Hopkins University School of Medicine
Dr. Yetrib Hathout, Ph.D.
Assistant Professor, Research Center for Genetic
Medicine,
Children’s National Medical Center
Professor Doan B. Hoang, Ph.D.
Director, ARN Networking Research Laboratory,
Faculty of Information Technology,
University of Technology, and
Honorary Associate,
Biomedical & Multimedia Information Technology
(BMIT) Research Group,

School of Information Technologies,
University of Sydney
Professor Eric P. Hoffman, Ph.D.
Clark Professor of Pediatrics, Biochemistry and
Molecular Biology, Neuroscience, & Genetics,
School of Medicine and Health Sciences,
George Washington University, and
Director, Research Center for Genetic Medicine,
Children’s National Medical Center
Professor H. K. Huang, D.Sc., FRCR(Hon.)
Professor and Director of Imaging Informatics,
Department of Radiology,
Keck School of Medicine,
University of Southern California,
Chair Professor of Medical Informatics
The Hong Kong Polytechnic University, and
Honorary Professor,
Shanghai Institute of Technical Physics,
The Chinese Academy of Sciences,
Professor Sung-Cheng Huang, D.Sc.
Department of Molecular and Medical
Pharmacology,
David Geffen School of Medicine,
University of California, Los Angeles (UCLA)
Dr. Emil Jovanov, Ph.D.
Electrical and Computer Engineering Department,
University of Alabama, Huntsville
Professor Peter Kazanzides, Ph.D.
Assistant Research Professor of Computer
Science,

The Johns Hopkins University
Dr. Jinman Kim, Ph.D.
Biomedical & Multimedia Information Technology
(BMIT) Research Group,
School of Information Technologies,
University of Sydney
xv
Mr. Peter M. Kuzmak, M.S.B.M.E.
Biomedical Engineer and Senior VistA Imaging
System Developer,
Health Provider Systems, VA Office of Information,
U.S. Department of Veterans Affairs (VA)
Dr. Eugene Y. S. Lim, Ph.D.
Hospital Scientist, Departments of PET and
Nuclear Medicine,
Royal Prince Alfred Hospital, Sydney, and
Honorary Associate,
Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Professor Brent J. Liu, Ph.D.
Deputy Director of Imaging Informatics,
Departments of Radiology and Biomedical Engineering,
Keck School of Medicine and Viterbi School
of Engineering,
University of Southern California
Dr. Zhenyu Liu, Ph.D.
Computer Science Department,
University of California, Los Angeles (UCLA)

Dr. Gladys Goh Lo, M.D.
Department of Diagnostic Radiology,
Hong Kong Sanatorium & Hospital
Professor Murray Loew, Ph.D.
Department of Electrical and Computer
Engineering,
George Washington University
Dr. Wenlei Mao, Ph.D.
Computer Science Department,
University of California, Los Angeles (UCLA)
Mr. Kevin Meldrum
Senior Architect and Computerized Patient
Record System Developer
Health Provider Systems, VA Office of Information
U.S. Department of Veterans Affairs (VA)
Dr. Aleksandar Milenkovic
´
, Ph.D.
Electrical and Computer Engineering Department,
University of Alabama, Huntsville
Dr. Javad Nazarian, Ph.D.
Research Center for Genetic Medicine,
Children’s National Medical Center
Dr. Dejan Ras
ˇ
kovic
´
, Ph.D.
Electrical and Computer Engineering Department,
University of Alaska

Erica Reeves
Research Center for Genetic Medicine,
Children’s National Medical Center
Dr. Abdul Roudsari, Ph.D.
Director, Centre for Health Informatics,
City University, London, UK
Dr. Andrew J. Simmonds, Ph.D.
Assistant Director, ARN Networking Research
Laboratory,
Faculty of Information Technology,
University of Technology, Sydney
Professor Nadine Smith, Ph.D.
Department of Bioengineering,
Penn State University
Dr. Seu Som, Ph.D.
Principal Medical Physicist
Department of Nuclear Medicine & PET,
Liverpool Hospital
Dr. Kenji Suzuki, Ph.D., SMIEEE
Assistant Professor of Radiology,
Department of Radiology,
University of Chicago
Dr. Damian M. Tan, Ph.D.
School of Electrical and Computer Engineering,
Science, Engineering & Technology Portfolio,
RMIT University
Professor Russell H. Taylor, Ph.D. FIEEE
Director, NSF Engineering Research Center
for CISST
Professor of Computer Science, with joint

appointments in Mechanical Engineering,
Radiology, and Surgery,
The Johns Hopkins University
Dr. Xiu Ying Wang, Ph.D.
Biomedical & Multimedia Information Technology
(BMIT) Research Group,
School of Information Technologies,
University of Sydney, and
School of Computer Science,
Heilongjiang University
Professor Yue Wang
, Ph.D.
Director, Computational Bioinformatics
and Bio-imaging Lab
Departments of Electrical, Computer,
and Biomedical Engineering,
Virginia Polytechnic Institute and State University
Professor Yu-Ping Wang, Ph.D.
Department of Computer Science and
Electrical Engineering,
University of Missouri—Kansas City
Dr. Zhiyong Wang, Ph.D.
Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Dr. Zuyi Wang, Ph.D.
Research Center for Genetic Medicine,
Children’s National Medical Center
Professor Andrew Webb, Ph.D., FIMBE

Director, Huck Institute Magnetic Resonance
Centre,
Department of Bioengineering,
Penn State University
Dr. Peter Weller, Ph.D.
Senior Lecturer in Medical Informatics,
Centre for Health Informatics,
City University, London, UK
Dr. Lingfeng Wen, Ph.D
Biomedical & Multimedia Information
Technology (BMIT) Research Group,
School of Information Technologies,
University of Sydney
Professor Anna M. Wu, Ph.D.
Department of Molecular and Medical
Pharmacology,
David Geffen School of Medicine,
University of California, Los Angeles (UCLA)
Professor Hong Ren Wu, Ph.D.
Professor of Visual Communications
Engineering,
Discipline Head, Computer and Network
Engineering,
School of Electrical and Computer Engineering,
Science, Engineering & Technology Portfolio,
RMIT University
Professor Chris Wyatt, Ph.D.
Departments of Electrical, Computer,
and Biomedical Engineering,
Virginia Polytechnic Institute and

State University
Dr. Kai-Ming Au Yeung,FRCR
Department of Diagnostic Radiology,
Hong Kong Sanatorium & Hospital
Dr. Xiaofeng Zhang, Ph.D.
Department of Bioengineering,
Penn State University
Dr. Qinghua Zou, Ph.D.
Computer Science Department,
University of California, Los Angeles (UCLA)
xvi
Introduction
We have all witnessed the revolutionary changes in recent years
brought about by the development of information technology.
These changes have been key to modernizing many disciplines
and industries, and biomedicine is no exception. The import-
ance of biomedical information technology has been widely
recognized and its application has expanded beyond the
boundary of health services, leading to the discovery of new
knowledge in life sciences and medicine. In the meantime, life
sciences and medicine are becoming an important driving
force for the further development of information technology
and related disciplines. Many emerging areas have recently
been developed, including health informatics, bioinformatics,
imaging informatics (or even medical imaging informatics; see
Chapter 13 of this book), medical biometrics, systems physi-
ology, systems biology, and biocybernetics. This book aims to
provide readers with a comprehensive and up-to-date overall
picture of information technology in biomedicine.
This book is divided into two major parts: technological

fundamentals and integrated clinical applications. The techno-
logical fundamentals cover key medical imaging systems: Elec-
tronic Medical Record (EMR) standards and systems; image
data compression; content-based medical image retrieval;
modeling and simulation; techniques for parametric imaging;
data processing and analysis; image registration and fusion;
visualization and display; data communication and transmis-
sion; security and protection for medical image data; and
biological computing. The integrated clinical applications
include picture archiving and communication systems (PACS)
and medical imaging informatics (MII) for filmless hospitals;
a knowledge-based digital library for retrieving scenario-
specific medical text documents; integrated multimedia
patient record systems; computer-aided diagnosis (CAD); clin-
ical decision support systems (CDSS); medical robotics and
computer-integrated interventional medicine; functional tech-
niques for brain magnetic resonance imaging; molecular
imaging in biology and pharmacology; the evolution of e-health
systems; and smart medical home. Most of the chapters include
over 100 references and comprehensively summarize the most
recent cutting-edge research in these areas.
This book is a well-designed research handbook instead of a
collection of research papers, and is intended for scientific and
clinical researchers and practitioners. It is also well-suited for
use as a textbook for senior undergraduate and junior post-
graduate students with exercises at the end of each chapter to
facilitate a better understanding of the comprehensive know-
ledge covered by this book. Ten chapters are contributed from
our Biomedical & Multimedia Information Technology
(BMIT) Research Group, School of Information Technologies,

University of Sydney and Centre for Multimedia Signal Pro-
cessing, Department of Electronic and Information Engineer-
ing, Hong Kong Polytechnic University, including from our
BMIT Group senior members Professor Michael Fulham, who
is an Adjunct Professor in the School of Information Tech-
nologies and Clinic Professor in the Faculty of Medicine,
University of Sydney, Director of PET and Nuclear Medicine
Departments, Royal Prince Alfred (RPA) Hospital, Clinical
Director for Medical Imaging Service Central Sydney Area
Health Services, Chairman of RPA PACS Steering Committee,
and the winner of the U.S. NIH Outstanding Performance in
Research Award and Australian Eccles Lectureship Award; and
Professor Doan B. Hoang, who is an Honorary Associate of the
School of Information Technologies, University of Sydney,
Professor of Computer Networks and Director of the ARN
Networking Research Laboratory, Faculty of Information
Technology, University of Technology, Sydney; as well as our
BMIT regular research collaborator and Chapter 3 co-author,
Professor Henry Wu, who is a Professor of Visual Communi-
cations Engineering and Discipline Head of Computer and
Network Engineering at the School of Electrical and Computer
Engineering, RMIT University, Melbourne, Australia. The fol-
lowing 13 chapters are purposely reserved for contributions
from other external international top-leading research groups
headed by the world’s authorities in their respective areas.
These international research leaders who contributed to
the remaining 13 chapters are introduced in the following
paragraphs.
Chapter 1: ‘‘Medical Imaging’’ is contributed by Professor
Andrew Webb, Director of Huck Institute Magnetic Resonance

Centre, and his team in the Department of Bioengineering at
Penn State University. Professor Webb’s main research pro-
gram is in high field applications of magnetic resonance
imaging and spectroscopy, with an emphasis on applications
to small animal imaging and microimaging. He has been a full
professor since 2003 and has published over 130 journal
articles in peer-reviewed publications. He is also the author
of a widely used textbook Introduction to Biomedical Imaging
(Wiley, 2003). Professor Webb is a Fellow of the American
Institute for Medical and Biological Engineering, as well as
having been awarded a Wolfgang Paul Prize from the
Humboldt Foundation from 2001 to 2004.
Chapter 5: ‘‘Data Modeling and Simulation’’ is contributed
by Professor Claudio Cobelli and his colleague Dr. Alessandra
Bertoldo at the Department of Information Engineering,
University of Padova, Italy. Professor Cobelli’s main research
subject, the field of modeling of endocrine-metabolic
systems, has received competitive research grants from
xvii
MIUR-MURST, EU and the U.S. National Institutes of Health.
He has been a full professor in bioengineering since 1981, and
has published over 228 papers in well-established internation-
ally refereed journals. He has also published a number of
international leading books in his area and is co-author
of Carbohydrate Metabolism: Quantitative Physiolog y and
Mathematical Modeling (Wiley, 1981), The Mathematical
Modeling of Metabolic and Endocrine Systems (Wiley, 1983),
Modeling and Control of Biomedical Systems (Pergamon Press,
1989), Modeling Methodology for Physiology and Medicine
(Academic Press, 2000), Tracer Kinetics in Bio medical Research:

from Data to Model (Kluwer Academic/Plenum Publishers,
2001), etc. Professor Cobelli, Fellow of IEEE, is an active
research leader, the founding Chairman of the International
Federation of Automatic Control (IFAC), Technical Commit-
tee on Modeling and Control for Biomedical Systems (includ-
ing Biological Systems), and is currently an Associate Editor of
IEEE Transactions on Biomedical Engineering and of Mathemat-
ical Biosciences and on the Editorial Board of the American
Journal of Physiology: Endocrinology and Metabolism.
Chapter 7: ‘‘Data Processing and Analysis’’ is contributed by
Professor Yue Wang’s group and his collaborators at the Vir-
ginia Polytechnic Institute and State University, University of
Missouri, Georgetown University, and George Washington
University. Professor Wang has also worked closely with the
Johns Hopkins Medical Institutions. His research focuses on
computational bioinformatics and bio-imaging for diagnosis
and molecular analysis of human diseases, with an emphasis
on the strategic frontier between statistical machine learning
and systems biomedical science. He leads a multidisciplinary
and multi-institutional research effort to improve the outcome
for patients with cancers, muscular dystrophies, and cardio-
vascular diseases, an initiative supported by the U.S. National
Institutes of Health and Department of Defense. His work has
also advanced the broad scientific fields of pattern recognition,
signal processing, statistical information visualization, and
machine learning. Professor Wang is an elected Fellow of the
American Institute for Medical and Biological Engineering
(AIMBE), and is currently an Associate Editor for the Inter-
national Journal of Biomedical Imaging, EURASIP Journal on
Bioinformatics and Systems Biology, and IEEE Signal Processing

Letters. Professor Wang is on the ISI (Web of Knowledge) list
of highly cited authors in the Category of Engineering.
Chapter 12: ‘‘Biologic Computing’’ is contributed by Pro-
fessor Eric P. Hoffman and his team at the Research Center for
Genetic Medicine, Children’s Medical Center, Washington
D.C. Dr. Hoffman is a Professor of Pediatrics, Biochemistry
and Molecular Biology, Neuroscience, and Genetics at the
George Washington University School of Medicine and Health
Sciences, and the Director of the Research Center for Genetic
Medicine, Children’s National Medical Center, Washington
D.C. He received his Ph.D. degree in biology (genetics) from
Johns Hopkins University in 1986 and subsequently worked as a
post-doctoral research fellow at the Harvard Medical School
and Children’s Hospital for two years. His laboratory is the top
contributor of Affymetrix microarray data in the public
domain, and he has focused bioinformatics methods develop-
ments on quality control and standard operating procedures,
signal/noise balance, and public access databases, including the
popular PEPR resource (). His
laboratory has enjoyed an impressive research grant track
record from NIH and Department of Defense, as well as
outstanding publication track record in the area of biological
computing in well-recognized journals, for example, Nature,
Cell, Nature Medicine, Neuron, Neurology, Brain, Journal of Cell
Biology, Journal of Biological Chemistry, and Bioinformatics.
Dr. Hoffman is among the most highly cited scientists (more
than 12,000 citations to date).
Chapter 13: ‘‘PACS and Medical Informatics for Filmless
Hospitals’’ is contributed by Professor H. K. (Bernie) Huang,
Director, and Professor Brent J. Liu, Deputy Director of In-

formatics, Department of Radiology, Keck School of Medicine,
University of Southern California. He is also the Chair Profes-
sor of Medical Informatics at Hong Kong Polytechnic Univer-
sity and an Honorary Professor at the Shanghai Institute
of Technical Physics and at the Chinese Academy of Sciences.
Professor Huang has pioneered PACS research, developed
the PACS at UCLA in 1991, and developed the hospital-inte-
grated PACS at UCSF in 1995. He has authored and co-
authored seven books, published over 200 peer-reviewed art-
icles, and received several patents. His book: PACS and Imaging
Informatics, published by John Wiley & Sons in 2004, is the
only textbook in this field. During the past 25 years, Professor
Huang has received over 21 million U.S. dollars in PACS,
medical imaging informatics, tele-imaging, and image-pro-
cessing–related research grants and contracts. He has mentored
22 Ph.D. students and over 30 post-doctoral fellows
from around the world. Professor Huang has been a consultant
for many national and international hospitals, imaging
manufacturers in the design and implementation of PAC sys-
tems, and enterprise level EPR with image distribution. He has
been a Visiting Professor in many leading universities around
the world and Board Member in leading medical imaging
manufacturers.
Chapter 14: ‘‘KMeX: A Knowledge-Based Digital Library for
Retrieving Scenario-Specific Medical Text Documents’’ is con-
tributed by Professor Welsey W. Chu and his team in the
Computer Science Department, University of California
(UCLA), Los Angeles. Professor Chu is a UCLA Distinguished
Professor and former chairman of the department. He received
his Ph.D. from Stanford University in 1966, worked with IBM

and Bell Laboratories from 1964 to 1966 and 1966 to 1969,
respectively, and has joined UCLA since 1969. During the first
two decades, he has made fundamental contributions to the
understanding of statistical multiplexing and did pioneering
work in file allocation, as well as directory design for distributed
databases and task partitioning in real-time distributive sys-
tems, for which he was elected as an IEEE Fellow. During the
xviii
past decade, his research interests have evolved to include intel-
ligent information systems and knowledge acquisition for large
information systems. Professor Chu led the development of
CoBase, a cooperative database system for structured data,
and KMed, a knowledge-based multimedia medical image sys-
tem. CoBase has been successfully used in logistic applications
to provide approximate matching of objects. Together with the
medical school staff, the KMed project has been extended to the
development of a medical digital library, which consists of
structured data, text documents, and images. The system pro-
vides approximate content-matching and navigation and serves
as a cornerstone for future paperless hospitals. In addition,
Professor Chu conducts research on data mining of large infor-
mation sources, knowledge-based text retrieval, and extending
the relaxation methodology to XML (CoXML) for information
exchange and approximate XML query answering in the Web
environment. In recent years, he also researches in the areas of
using inference techniques for data security and privacy protec-
tion (ISP). Professor Chu has received best paper awards at the
19th International Conference on Conceptual Modeling in 2000
for his work on XML/Relational schema transformation. He
and his students have received best paper awards at the Ameri-

can Medical Information Association Congress in 2002 and
2003 for indexing and retrieval of medical free text, and have
also been awarded a Certificate of Merit for the Medical Digital
Library Demo System at the 89th Annual Meeting of the Radio-
logical Society of North America in 2003. He is also the recipient
of the IEEE Computer Society 2003 Technical Achievement
Award for his contributions to intelligent information systems.
Chapter 15: ‘‘Integrated Multimedia Patient Record Sys-
tems’’ is contributed by Dr. Ruth E. Dayhoff and her Multi-
media Medical Record group, which is part of the Office of
Information of the U.S. Department of Veterans Affairs (VA).
This organization is responsible for the software and systems
used by the clinicians and staff at 156 VA hospitals and almost
900 clinics, the largest health care network in the United States.
The VA’s software, called Veterans Health Information System
& Technology Architecture (VistA) is developed by the VA’s
Office of Information. Initial work started over 25 years ago,
and over 60 different hospital information system modules are
in use. VistA Imaging, the multimedia patient record compon-
ent, has grown and evolved over the past 16 years. Dr. Ruth
Dayhoff, M.D., is a physician and early pioneer in medical
informatics. She directs the VistA Imaging development
team. The team participates in integrating the Healthcare
Enterprise initiatives and other major health care standards.
The VistA System is undergoing a major data standardization
effort necessitated by the new capabilities to view and filter a
patient’s entire record, including information stored at remote
sites. This work involves domains such as orders, progress note
titles, problems, and imaging procedures. Another major focus
within the VA is monitoring the quality of health care that is

provided. Software plays a major role in this effort, and is
constantly enhanced to provide additional reminders to clini-
cians and monitoring tools for the organization. As a result,
the Department of Veterans Affairs has recently been recog-
nized by multiple authorities as providing the highest quality
health care in the United States.
Chapter 16: ‘‘Computer-Aided Diagnosis’’ is contributed by
Professor Maryellen L. Giger and her colleague Kenji Suzuki
at the University of Chicago. Dr. Giger is a Professor of
Radiology and resides on the Committee on Medical Physics
at the University of Chicago, is the Director of the Graduate
Programs in Medical Physics, and oversees her research lab of
12 members, including post-doctoral trainees, research asso-
ciates, and graduate students. She also serves as Chief of the
Radiological Sciences Section and Vice Chair for Basic Science
Research in the Department of Radiology, University of Chi-
cago. Dr. Giger received her Ph.D. in medical physics from
the University of Chicago in 1985. Dr. Giger is recognized as
one of the pioneers in the development of computer-aided
diagnosis. She has authored or co-authored more than 240
scientific manuscripts (including 120 peer-reviewed journal
articles), is inventor/co-inventor on approximately 25 patents,
and serves as a reviewer for various granting agencies, includ-
ing the NIH and the U.S. Army. Dr. Giger is an Associate
Editor for Medical Physics and IEEE Transactions on Medical
Imaging. She is an elected fellow of the American Institute for
Medical and Biological Engineering (AIMBE) and the Ameri-
can Association of Physicists in Medicine (AAPM), and serves
on various scientific program committees. During recent
years, she has been invited to give presentations on CAD

at SPIE, BIROW, SCAR, IWDM, CARS, AAPM, and RSNA,
as well as presentations at various workshops and conferences
of the NCI. Her research interests include digital radio-
graphy and computer-aided diagnosis in multi-modality
breast imaging, chest/CT imaging, cardiac imaging, and
bone radiography.
Chapter 17: ‘‘Clinical Decision Support Systems’’ is contrib-
uted by Professor Ewart Carson and his colleagues, Dr. Abdul
Roudsari, and Dr. Peter Weller at the Centre for Health In-
formatics, City University, London, UK. Professor Carson is a
Professor of Systems Science, and for many years was the
Director of the Centre for Measurement and Information in
Medicine at City University, which has now been restructured
as the Centre for Health Informatics. He served as the Director
of the Institute of Health Sciences from 1993 to 1999. His areas
of research interest and expertise include modeling in
physiology and medicine; modeling methodology for health
resource management; clinical decision support systems;
development and evaluation of model-based decision support
systems; evaluation methodologies with particular application
in telemedicine; and integrated policy modeling for ICT
enhanced public health care. He has led a range of major
research projects funded by UK and European agencies, and
has successfully supervised some 40 Ph.D. students. Publica-
tions include some 13 authored and edited books and more
than 300 journal papers and book chapters. Dr. Carson is a
xix
member of the Executive Team of the Healthcare Technologies
Professional Network of the IEEE, Associate Editor of Com-
puter Methods and Programs in Biomedicine, a Technical

Board member of the International Federation of Automatic
Control (IFAC), and Chairman of the IFAC Coordinating
Committee for Biological and Ecological Systems. He is an
Honorary Member of the Royal College of Physicians (Lon-
don), Fellow of IEEE, Fellow of the American Institute of
Medical and Biological Engineers, and Fellow of the Inter-
national Academy of Medical and Biological Engineering.
Due to his exceptional outstanding contributions in his field,
he received the 2005 IEEE Engineering in Medicine and Biol-
ogy Career Achievement Award.
Chapter 18: ‘‘Medical Robotics and Computer-Integrated
Interventional Medicine’’ is contributed by Professor Russell
H. Taylor and Dr. Peter Kazanzides from Johns Hopkins
University. Professor Taylor received a B.E.S. degree from
The Johns Hopkins University in 1970 and a Ph.D. in Com-
puter Science from Stanford in 1976. He joined IBM Research
in 1976, where he developed the AML robot language and
various other projects, managed robotics and automation
technology research activities from 1982 to 1988, led the
team that developed the first prototype for the Robodoc
1
system for robotic hip replacement surgery from 1988 to
1989, and served as the Manager of Computer Assisted Sur-
gery from 1990 to 1995. In September 1995, Dr. Taylor moved
to Johns Hopkins University as a Professor of Computer
Science, with joint appointments in Radiology, Surgery, and
Mechanical Engineering. He is the Director of the NSF En-
gineering Research Center for Computer-Integrated Surgical
Systems and Technology and is also currently on the Scientific
Advisory Board of Integrated Surgical Systems for IBM, where

he subsequently developed novel systems for computer-
assisted craniofacial surgery and robotically-augmented endo-
scopic surgery. At Johns Hopkins, he has worked on all
aspects of CIIM systems, including modeling, registration,
and robotics in areas including percutaneous local therapy,
microsurgery, and minimally-invasive robotic surgery. He is
Editor Emeritus of the IEEE Transactions on Robotics and
Automation, Fellow of IEEE and AIMBE. In February, 2000
he received the Maurice Mu
¨
ller award for excellence in com-
puter-assisted orthopaedic surgery. Dr. Kazanzides received a
Ph.D. in electrical engineering from Brown University in
1988, and began work on surgical robotics in March 1989 at
IBM Research with Dr. Russell Taylor. Dr. Kazanzides co-
founded Integrated Surgical Systems (ISS) in November,
1990 to commercialize the robotic hip replacement research
performed at IBM and the University of California, Davis. As
Director of Robotics and Software, he was responsible for the
design, implementation, validation, and support of the
ROBODOC1 hardware and software. In 2002, Dr. Kazan-
zides joined the NSF Engineering Research Center for Com-
puter-Integrated Surgical Systems and Technology (CISST
ERC) at Johns Hopkins University.
Chapter 20: ‘‘Molecular Imaging in Cancer’’ is contrib-
uted by Professor Zaver M. Bhujwalla and her colleagues,
Dr. Kristine Glunde and Dr. Catherine A. Foss in the Depart-
ments of Radiology and Oncology at the Johns Hopkins
University School of Medicine. Professor Bhujwalla joined
the Department of Radiology at the Johns Hopkins University

School of Medicine in 1989 after completing her Ph.D. from
the University of London and has built an internationally-
recognized cancer functional and molecular imaging program
at Johns Hopkins. She is currently the Director of the JHU
In Vivo Cellular and Molecular Imaging Center (JHU ICMIC
Program), and Director of the Cancer Imaging Resource of
the Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins. Over the past decade, Dr. Bhujwalla’s work has
focused on the application of imaging technology to promote
the understanding of cancer. These studies encompass study-
ing cancer from the sub-cellular to the clinical stage with
imaging, with a strong impact on both basic scientific research
and clinical applications.
Chapter 21: ‘‘Molecular Imaging in Biology and Pharma-
cology’’ is contributed by Professor Henry Sung-Cheng Huang
and his colleagues in the Department of Molecular and Med-
ical Pharmacology, David Geffen School of Medicine, UCLA.
Professor Huang has pioneered the quantification of PET
images and was involved in the tomography reconstruction
of early PET scanners in the early 1970s. He has investigated a
series of radioactivity quantification issues in PET imaging,
including photon attenuation correction scheme for PET, that
have had a lasting impact on all biomedical imaging fields. He
is a pioneer in using compartmental models to model the
kinetic behavior of positron-labeled tracers (started in the
late 1970s). His modeling papers on FDG in 1979 and 1980
have shaped the way glucose utilization rates in local tissue are
currently measured in vivo. He has expanded its application
from brain tissue to myocardium and to tumors, and from
research to the clinical setting. His early papers are still fre-

quently quoted in the literature, and the model continues to be
used in the field. In addition to the FDG modeling, Dr. Huang
has developed models and study methodologies for many
other PET tracers as well, including O-15 water/oxygen, N-13
ammonia, C-11 Palmitate, C-11 acetate, FESP, and FDOPA. In
conjunction with biologists/physicians, Professor Huang has
demonstrated the value of quantitative biomedical imaging
and has advanced our understanding of the biological/physio-
logical changes in diseases. He has also made exceptional out-
standing contributions in many related areas and has over 800
peer-reviewed publications (including 293 full journal papers
in well-established journals, 488 peer-reviewed short papers/
abstracts in well-established journals and keynote/invited/spe-
cial presentation articles, 22 book chapters, and three U.S.
patents and software copyrights) with frequent citations. He
has served as Deputy Chief Editor, Associate Editor or editorial
board consultant for major journals in his areas, for example,
Cerebral Blood Flow and Metabolism, Molecular Imaging
xx
and Biology, and Journal of Nuclear Medicine. He has received
numerous prestigious awards, such as George Von Hevesy
Prize, Award of Excellence for Best Paper, and Outstanding
Scientist Award.
Chapter 22: ‘‘From Telemedicine to Ubiquitous M-Health:
The Evolution of E-Health Systems’’ is contributed by Dr. Dejan
Ras
ˇ
kovic
´
from the University of Alaska, Fairbanks, who leads

the DIA-sponsored Laboratory for Energy and Performance
Profiling of Wireless Sensor Networks and performs research
in wireless sensor networks, battery-aware processing, and em-
bedded systems architecture. Contributing authors include Dr.
Piet C. De Groen from the Mayo Clinic, who is a Professor of
Medicine and former Program Director of Mayo Clinic/IBM
Computational Biology Collaboration at the Mayo Clinic,
Rochester, and Drs. Aleksandar Milenkovic
´
and Emil Jovanov
from the University of Alabama in Huntsville. The wearable
health monitoring group at the University of Alabama has
been developing wireless intelligent sensors and wearable
health sensors for more than seven years (.
edu/$jovanov/whrms/). The group has pioneered the concept of
the wireless body area network of intelligent sensors (WBAN) for
ambulatory health monitoring, and developed a few dozens
different sensors and systems for wearable health monitoring.
Their wireless distributed system for stress monitoring has been
used at the Navy Aviation Medical Research Lab at Pensacola,
Florida for more than four years. They have established a collab-
oration with the Mayo Clinic in Rochester, MN, and currently
work on wearable ambulatory monitoring.
Professor David Dagan Feng
Professor, School of Information Technologies,
University of Sydney, and
Chair-Professor of Information Technology,
Hong Kong Polytechnic University
xxi
I

Technological
Fundamentals
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1
Medical Imaging
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Digital Radiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.1 Formation and Characteristics of X-rays
:
1.2.2 Scatter and Attenuation of
X-rays in Tissue
:
1.2.3 Instrumentation for Digital Radiography
1.3 Computed Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.1 Principles of Computed Tomography
:
1.3.2 Spiral and Multislice Computed
Tomography
1.4 Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.4.1 Radioactive Nuclides in Nuclear Medicine
:
1.4.2 Nuclear Medicine
Detectors
:
1.4.3 Single Photon Emission Computed Tomography
:
1.4.4 Positron
Emission Tomography
:
1.4.5 Combined Positron Emission Tomography/Computed

Tomography Scanners
1.5 Ultrasonic Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.5.1 Fundamentals of Ultrasound
:
1.5.2 Transducers and Beam
Characteristics
:
1.5.3 Image Acquisition and Display
1.6 Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.6.1 Basis of Magnetic Resonance
:
1.6.2 Magnetic Field Gradients
:
1.6.3 Fourier
Imaging Techniques
:
1.6.4 Magnetic Resonance Imaging Contrast Agents
1.7 Diffuse Optical Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.7.1 Propagation of Light Through Tissue
:
1.7.2 Measurement of Blood
Oxygenation
:
1.7.3 Image Reconstruction
:
1.7.4 Measurement Techniques
1.8 Biosignals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.8.1 Electroencephalography
:
1.8.2 Electrocardiograms

1.9 Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
A.1 Fourier Transforms
:
A.2 Filtered Backprojection
:
A.3 Iterative Image
Reconstruction
1.10 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
1.11 References and Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
1.1 Introduction
Medical imaging forms a key part of clinical diagnosis, and
improvements in the quality and type of information available
from such images have extended the diagnostic accuracy and
range of new applications in health care. Previously seen as the
domain of hospital radiology departments, recent techno-
logical advances have expanded medical imaging into neurol-
ogy, cardiology, and cancer centers, to name a few. The past
decade, in particular, has seen many significant advances in
each of the imaging methods covered in this chapter. Since
there are a large number of texts (see Bibliography) that deal in
great detail with the basic physics, instrumentation, and clin-
ical applications of each imaging modality, this chapter sum-
marizes these aspects in a succinct fashion and emphasizes
recent technological advances. State-of-the-art instrumenta-
tion for clinical imaging now comprises, for example, 64-slice
spiral computed tomography (CT); multi-element, multidi-
mensional phased arrays in ultrasound; combined positron
emission tomography (PET) and CT scanners; and rapid par-
allel imaging techniques in magnetic resonance imaging (MRI)
using large multidimensional coil arrays. Furthermore, on the

horizon are developments such as integrated diffuse optical
tomography (DOT)/MRI. Considered together with signifi-
cant developments in new imaging contrast agents—so-called
‘‘molecular imaging agents’’—the role of medical imaging
looks likely to continue to expand in modern-day health
care.
Dr. Xiaofeng Zhang,
Prof. Nadine Smith, and
Prof. Andrew Webb
Penn State University
3
Copyright ß 2008 by Elsevier, Inc.
All rights of reproduction in any form reserved.