From Signals to Image A Basic Course on Medical Imaging

for Engineers

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Preface

Over the past three decades, we have developed and taught an introductory medical
imaging course at the Technion-IIT for senior engineering students and graduate
students. Within the limiting timeline of a single university course, we attempted to
lay the foundations needed for working and conducting research in this fascinating
field of medical imaging. The goal has been to introduce the students to the most
prominent modalities in current medical imaging, present the principles of image
reconstruction and convey the very basic physical, engineering, and mathematical
methods that underlie each one of them or are common to all. Consequently, the
topics range from the physical phenomena used for data acquisition, the constraints
posed to imaging device design, and the elementary mathematics of image recon-
struction. Given this broad scope, the course provides the essential basics for further
self-study or for advanced courses specializing in particular modalities. No less
important, was the goal of conveying an enthusiasm for working with medical
scanners, since our local industry has made substantial contributions to the field.
This textbook is a summary of our introductory medical imaging course for
engineers. The authors are grateful to those who have produced excellent texts on
various topics in medical imaging which are referenced throughout the text for
students who need a more comprehensive understanding. By introducing the prin-
ciples used in medical imaging scanners, this textbook provides students with a
context for new developments in the field. The chapters dealing with X-ray and
X-ray CT, gamma cameras, positron emission tomography, ultrasound, and mag-
netic resonance imaging (MRI) are generally structured to address the physical
phenomena, signal sources, data acquisition, and image formation. Some clinical
examples and examples of quality control are also provided. General concepts are
presented in an introductory chapter and a chapter on image reconstruction. Exem-
plary questions for each chapter and final exams with their solutions provide a tool
for evaluating the students’ ability to apply the principles, with many questions

vii
viii Preface

based on practical issues with device design or operation in the clinic. We believe
this textbook can greatly aid both instructors and engineering students in an intro-
ductory course on medical imaging.
We are grateful to all our friends and colleagues in academia, in the clinic, and in
the industry who have contributed to our course development throughout these many
years and for sharing images and knowledge which eventually led to this textbook.
We trust that readers will enjoy it and find it useful.

Haifa, Israel Haim Azhari

p.s.
Although we did our best, there are probably quite a number of things to correct and improve. We
would highly appreciate any comments sent to me or John by E-mail. Kindly indicate: “Medical
Imaging book - Comments” in the subject. Thank you in advance.
John: [email protected]
Haim: [email protected]
Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Historical Background and Motivation . . . . . . . . . . . . . . . . . . . . 1
1.1.1 X-Rays and CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.2 Nuclear Medicine: Gamma Camera, SPECT, and PET . . 3
1.1.3 Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.4 MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.1.5 Other Imaging Modalities . . . . . . . . . . . . . . . . . . . . . . . 5
1.2 Basic Definitions of Medical Imaging . . . . . . . . . . . . . . . . . . . . . 6
1.2.1 What Is a Medical Image? . . . . . . . . . . . . . . . . . . . . . . 6
1.2.2 Mapping of an Object into Image Domain . . . . . . . . . . . 8
1.2.3 What Are the Required Stages for Developing
an Imaging Modality? . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.3 Basic Features of an Image . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.1 Gray Levels and Dynamic Range . . . . . . . . . . . . . . . . . 12
1.3.2 Point Spread Function and Line Spread Function . . . . . . 16
1.3.3 Image Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.3.4 Spatial Frequencies . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
1.3.5 Modulation Transfer Function (MTF) . . . . . . . . . . . . . . 29
1.3.6 Contrast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
1.3.7 Image Noise and Artifacts . . . . . . . . . . . . . . . . . . . . . . 33
1.3.8 Signal-to-Noise Ratio (SNR) and Contrast-to-Noise
Ratio (CNR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
1.3.9 Detectability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.3.10 The Receiver Operator Curve (ROC) . . . . . . . . . . . . . . . 39
1.4 Standard Views in Radiology . . . . . . . . . . . . . . . . . . . . . . . . . . 42
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2 Basic Principles of Tomographic Reconstruction . . . . . . . . . . . . . . . . 45
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
2.2 Part I: Basic Principles of Tomography . . . . . . . . . . . . . . . . . . . 47
2.2.1 Projections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
ix
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2.2.2 Tomographic Data Acquisition: The “Sinogram”

and the Radon Transform . . . . . . . . . . . . . . . . . . . . . . . 52
2.2.3 Back Projection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2.2.4 Algebraic Reconstruction Tomography (ART):
The Projection Differences Method . . . . . . . . . . . . . . . . 58
2.2.5 Algebraic Reconstruction Tomography (ART):
The Projection Ratio Method . . . . . . . . . . . . . . . . . . . . 63
2.2.6 The Weight Matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.2.7 The Tomographic Slice Theorem . . . . . . . . . . . . . . . . . 66
2.2.8 “Filtered Back Projection” (FBP) . . . . . . . . . . . . . . . . . 69
2.2.9 The Needed Number of Projections . . . . . . . . . . . . . . . . 75
2.2.10 Spiral CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
2.2.11 Fan Beam Reconstruction . . . . . . . . . . . . . . . . . . . . . . . 78
2.3 Part II: Advanced Reconstruction Algorithms . . . . . . . . . . . . . . . 80
2.3.1 Difference ART Convergence . . . . . . . . . . . . . . . . . . . . 80
2.3.2 Advanced Multiplicative ART . . . . . . . . . . . . . . . . . . . 83
2.3.3 Statistical Reconstruction Approaches . . . . . . . . . . . . . . 84
2.3.4 Other Image Reconstruction Approaches . . . . . . . . . . . . 92
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
3 X-Ray Imaging and Computed Tomography . . . . . . . . . . . . . . . . . . 95
3.1 X-Rays: Physical Phenomena . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.1.1 X-Ray Tubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.1.2 X-Ray Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
3.1.3 X-Ray Interaction with Body Tissues . . . . . . . . . . . . . . 101
3.2 Projectional Radiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
3.2.1 Detection and Data Acquisition . . . . . . . . . . . . . . . . . . . 106
3.2.2 Image Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
3.2.3 Projectional X-Ray Types and Modalities . . . . . . . . . . . 115
3.2.4 X-Ray Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . 119
3.3 X-Ray CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
3.3.1 Basic Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
3.3.2 CT Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
3.3.3 Detection and Signal Sources . . . . . . . . . . . . . . . . . . . . 128
3.3.4 Image Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
3.3.5 Axial Scans and Helical Scans . . . . . . . . . . . . . . . . . . . 134
3.3.6 Image Manipulation and Clinical Examples . . . . . . . . . . 137
3.4 Dosimetry and Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
3.4.1 Ionizing Radiation and Health Risks . . . . . . . . . . . . . . . 143
3.4.2 The ALARA Concept . . . . . . . . . . . . . . . . . . . . . . . . . 149
3.4.3 Quality Versus Safety . . . . . . . . . . . . . . . . . . . . . . . . . . 150
3.5 Emerging Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
3.5.1 Dual-Energy CT (DECT) . . . . . . . . . . . . . . . . . . . . . . . 152
3.5.2 Multi-energy CT and Photon Counting . . . . . . . . . . . . . 154
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
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4 Nuclear Medicine: Planar and SPECT Imaging . . . . . . . . . . . . . . . . 159

4.1 Physical Phenomena . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
4.1.1 Physics of Radioisotopes and Radioactive Decay . . . . . . 160
4.1.2 Propagation and Attenuation of Ionizing Radiation . . . . . 165
4.1.3 Radiation Safety with Open Sources . . . . . . . . . . . . . . . 167
4.2 Signal Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
4.2.1 Emission Versus Transmission Scanning . . . . . . . . . . . . 170
4.2.2 Concept of a Radiopharmaceutical . . . . . . . . . . . . . . . . 171
4.2.3 Gamma Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
4.2.4 Bremsstrahlung Sources . . . . . . . . . . . . . . . . . . . . . . . . 175
4.2.5 Radiotracer Production . . . . . . . . . . . . . . . . . . . . . . . . . 176
4.3 Data Acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
4.3.1 Collimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
4.3.2 Scintillation Crystals . . . . . . . . . . . . . . . . . . . . . . . . . . 181
4.3.3 Photomultiplier Tubes . . . . . . . . . . . . . . . . . . . . . . . . . 182
4.3.4 Positioning Circuits . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
4.3.5 Solid-State Detectors . . . . . . . . . . . . . . . . . . . . . . . . . . 187
4.3.6 SPECT Rotating Gantry Methods . . . . . . . . . . . . . . . . . 189
4.3.7 SPECT Stationary Gantry Methods . . . . . . . . . . . . . . . . 190
4.3.8 Gating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
4.3.9 Hybrid SPECT/CT Systems . . . . . . . . . . . . . . . . . . . . . 192
4.4 Image Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
4.4.1 Planar Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
4.4.2 Dynamic Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
4.4.3 Image Digitization, Storage, and Display . . . . . . . . . . . . 195
4.4.4 SPECT Image Reconstruction . . . . . . . . . . . . . . . . . . . . 197
4.4.5 Attenuation Correction . . . . . . . . . . . . . . . . . . . . . . . . . 198
4.4.6 Scatter Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
4.4.7 Resolution Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . 203
4.4.8 Post-Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
4.4.9 Hybrid Image Fusion . . . . . . . . . . . . . . . . . . . . . . . . . . 206
4.4.10 Quality Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
4.5 Clinical Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
4.6 Challenges and Emerging Directions . . . . . . . . . . . . . . . . . . . . . 211
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
5 Positron Emission Tomography (PET) . . . . . . . . . . . . . . . . . . . . . . . 217
5.1 Physical Phenomena . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
5.1.1 Radioactive Decay and Positron Emission . . . . . . . . . . . 218
5.1.2 Particle/Anti-particle Annihilation . . . . . . . . . . . . . . . . . 218
5.1.3 Coincident Photon Pairs . . . . . . . . . . . . . . . . . . . . . . . . 220
5.2 Signal Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
5.2.1 Emission Versus Transmission Scanning . . . . . . . . . . . . 220
5.2.2 F-18 FDG: [18F]-2-Fluoro-2-deoxy-D-glucose . . . . . . . . 221
5.2.3 Other Positron Emission Radiotracers . . . . . . . . . . . . . . 221
xii Contents

5.3 Data Acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

5.3.1 Physical Collimation: Septa . . . . . . . . . . . . . . . . . . . . . 225
5.3.2 Electronic Collimation: Coincident Photon Detection . . . 225
5.3.3 3D Acquisition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
5.3.4 Time-of-Flight Acquisitions . . . . . . . . . . . . . . . . . . . . . 229
5.3.5 Calibration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
5.3.6 Noise Equivalent Count Rate . . . . . . . . . . . . . . . . . . . . 232
5.3.7 Solid-State Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
5.3.8 Hybrid PET/CT Systems . . . . . . . . . . . . . . . . . . . . . . . 234
5.4 Image Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
5.4.1 Tomographic Principle . . . . . . . . . . . . . . . . . . . . . . . . . 235
5.4.2 Image Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . 235
5.4.3 Attenuation Correction . . . . . . . . . . . . . . . . . . . . . . . . . 236
5.4.4 Scatter Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
5.4.5 Point Spread Function Modelling . . . . . . . . . . . . . . . . . 240
5.4.6 Post-Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
5.4.7 Quantitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
5.4.8 Hybrid Image Fusion . . . . . . . . . . . . . . . . . . . . . . . . . . 243
5.4.9 Quality Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
5.5 Clinical Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
5.6 Challenges and Emerging Directions . . . . . . . . . . . . . . . . . . . . . 247
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
6 Magnetic Resonance Imaging (MRI) . . . . . . . . . . . . . . . . . . . . . . . . . 253
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
6.2 The Nuclear Magnetic Resonance (NMR) Phenomenon . . . . . . . . 254
6.3 Associated Physical Phenomena . . . . . . . . . . . . . . . . . . . . . . . . 256
6.3.1 Magnetic Fields . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
6.3.2 Magnetic Susceptibility: The Response of Matter
to Magnetic Fields . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
6.3.3 Magnetization of the Hydrogen Nucleus . . . . . . . . . . . . 259
6.3.4 The Magnetic Moment and Its Response
to an External Magnetic Field . . . . . . . . . . . . . . . . . . . . 263
6.3.5 Precession . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
6.3.6 The Rotating Reference Frame . . . . . . . . . . . . . . . . . . . 266
6.3.7 The Magnetic Field B1 . . . . . . . . . . . . . . . . . . . . . . . . . 267
6.3.8 Off-Resonance and the Effective Field B1
(For Advanced Reading) . . . . . . . . . . . . . . . . . . . . . . . . 269
6.3.9 The MRI Signal Source . . . . . . . . . . . . . . . . . . . . . . . . 271
6.3.10 The Spin-Lattice and Spin-Spin Relaxation Processes . . . 273
6.3.11 The Bloch Equations . . . . . . . . . . . . . . . . . . . . . . . . . . 276
6.4 MRI Contrast Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
6.5 Spatial Mapping: The Field Gradients . . . . . . . . . . . . . . . . . . . . 279
6.6 Spatial Mapping: Slice Selection . . . . . . . . . . . . . . . . . . . . . . . . 282
Contents xiii

6.7 K-Space Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

6.7.1 Traveling in K-Space . . . . . . . . . . . . . . . . . . . . . . . . . . 289
6.8 Imaging Protocols and Pulse Sequences . . . . . . . . . . . . . . . . . . . 293
6.9 Some Important Pulse Sequences (Advanced Reading) . . . . . . . . 298
6.9.1 Inversion Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
6.9.2 Spin Echo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
6.9.3 Fast or Turbo Spin Echo . . . . . . . . . . . . . . . . . . . . . . . . 305
6.9.4 Echo Planar Imaging (EPI) . . . . . . . . . . . . . . . . . . . . . . 307
6.9.5 Steady State . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
6.9.6 Advanced Rapid Imaging Methods . . . . . . . . . . . . . . . . 312
6.10 Three-Dimensional (3D) Imaging . . . . . . . . . . . . . . . . . . . . . . . . 312
6.11 Magnetic Resonance Angiography (MRA) . . . . . . . . . . . . . . . . . 313
6.11.1 MRA Using Contrast-Enhancing Material (CEM) . . . . . . 314
6.11.2 Time-of-Flight (TOF) MRA . . . . . . . . . . . . . . . . . . . . . 315
6.11.3 Phase Contrast MRA . . . . . . . . . . . . . . . . . . . . . . . . . . 317
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
7 Ultrasound Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
7.2 Physical Phenomena . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
7.2.1 Speed of Sound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
7.2.2 Attenuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
7.2.3 The Acoustic Impedance . . . . . . . . . . . . . . . . . . . . . . . 326
7.2.4 Reflection Refraction and Transmission . . . . . . . . . . . . . 328
7.2.5 The Doppler Shift Effect . . . . . . . . . . . . . . . . . . . . . . . 330
7.3 Ultrasonic Transducers and Acoustic Fields . . . . . . . . . . . . . . . . 331
7.3.1 Piezoelectric Transducers . . . . . . . . . . . . . . . . . . . . . . . 331
7.3.2 Single Element Transducers . . . . . . . . . . . . . . . . . . . . . 333
7.3.3 Linear Phased Array Transducers . . . . . . . . . . . . . . . . . 335
7.3.4 Implications on Image Resolution . . . . . . . . . . . . . . . . . 336
7.4 Imaging Modes and Image Formation . . . . . . . . . . . . . . . . . . . . 338
7.4.1 The Signal Source . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
7.4.2 The A-Line (A-Mode) . . . . . . . . . . . . . . . . . . . . . . . . . . 341
7.4.3 The Time Gain Correction (TGC) . . . . . . . . . . . . . . . . . 344
7.4.4 The M-Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
7.4.5 The B-Scan (2D Imaging) . . . . . . . . . . . . . . . . . . . . . . . 347
7.4.6 Three-Dimensional (3D) and Four-Dimensional (4D)
Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
7.4.7 Through-Transmission Imaging . . . . . . . . . . . . . . . . . . . 351
7.5 Doppler Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
7.5.1 Single Zone Velocity Imaging . . . . . . . . . . . . . . . . . . . . 354
7.5.2 Two-Dimensional (2D) Doppler and Color
Flow Mapping (CFM) . . . . . . . . . . . . . . . . . . . . . . . . . 357
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7.6 Advanced Imaging Techniques . . . . . . . . . . . . . . . . . . . . . . . . . 359

7.6.1 Contrast-Enhanced Ultrasound (CEUS) Imaging . . . . . . 359
7.6.2 Elastography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
7.6.3 Ultrafast Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

Exemplary Questions for Chap. 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365

Solutions to Exemplary Questions for Chap. 1 . . . . . . . . . . . . . . . . . . . . 369

Exemplary Questions for Chap. 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

Solutions to Exemplary Questions for Chap. 2 . . . . . . . . . . . . . . . . . . . . 379

Exemplary Questions for Chap. 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387

Solutions to Exemplary Questions for Chap. 3 . . . . . . . . . . . . . . . . . . . . 393

Exemplary Questions for Chap. 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399

Solutions to Exemplary Questions for Chap. 4 . . . . . . . . . . . . . . . . . . . . 403

Exemplary Questions for Chap. 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409

Solutions to Exemplary Questions for Chap. 5 . . . . . . . . . . . . . . . . . . . . 413

Exemplary Questions for Chap. 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

Solutions to Exemplary Questions for Chap. 6 . . . . . . . . . . . . . . . . . . . . 427

Exemplary Questions for Chap. 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433

Solutions to Exemplary Questions for Chap. 7 . . . . . . . . . . . . . . . . . . . . 439

Medical Imaging: Final Exam A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441

Solutions to Exemplary Exam A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449

Medical Imaging: Final Exam B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453

Solutions to Exemplary Exam B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
Chapter 1
Introduction

Synopsis: In this chapter the reader is introduced to the basic concepts and
useful terms applied in medical imaging.
The learning outcomes are: The reader will know what is expected from a
medical image, will comprehend the issues involved in generating and
assessing the quality of a medical image, and will be able to implement
(conceptually) this knowledge in the development of a new imaging modality.

1.1 Historical Background and Motivation

1.1.1 X-Rays and CT

The saying “A picture is worth a thousand words” is well accepted as true in many
fields of life. This statement is particularly valid in the context of medicine. For
thousands of years, medicine lacked the ability to implement, for diagnosis purposes,
our most efficient sense, i.e., vision, in examining the internal structure of the human
body. Palpation was the most commonly implemented tool. However, palpation can
hardly reveal a small fraction of the numerous existing pathologies. Hence, physi-
cians were as helpless as “The blind gropeth in darkness” [1].
The major breakthrough occurred on November 8, 1895, when Wilhelm Conrad
Röntgen found that when activating a cathode ray tube enclosed in a sealed thick
black carton in a dark room, a paper plate covered on one side with barium
platinocyanide placed near the tube became fluorescent, indicating a new type of
ray. These invisible rays, later termed x-rays, passed through matter that was opaque
to visible light rays. Soon after, grasping the potential of his discovery, he produced

© Springer Nature Switzerland AG 2020 1

H. Azhari et al., From Signals to Image,
https://doi.org/10.1007/978-3-030-35326-1_1
2 1 Introduction

Fig. 1.1 The first x-ray

image produced by
Roentgen depicting his
wife’s hand and ring. (From
Wikimedia)

the very first medical image of his wife’s hand [2], showing its internal structure.
This famous roentgenogram is depicted in Fig. 1.1.
Within several months after publication of the discovery [3], roentgenograms
were produced in battlefields to help locate bullets in soldiers who had been injured
[4]. However, the need for using very high voltage created difficulty in its medical
use. This changed in 1913, when Coolidge introduced a more practical design of
high vacuum x-ray tube with a heated cathode that produced reliably high-intensity
beams. Ever since, the application of x-rays in medicine has increased exponentially
with improved equipment and with the more recent use of digital systems and
displays. Several billions of planar x-ray images are currently produced annually
worldwide.
A quantum leap in this area occurred on October 1, 1971, when the first computed
tomography (CT) clinical image was produced by Godfrey Hounsfield and his
colleagues [5]. The system which collected information via the rotation of an x-ray
imaging system about a patient and applied computer reconstruction was able to
produce a new kind of image. For the first time, cross-sectional images of the intact
brain depicting its anatomy were available in a noninvasive manner. This event best
designates the “Bagel Era,” when scanners with a circular structure became domi-
nant in the field of medical imaging. The progress and improvements continuously
introduced into scanning technology have been strongly tied to the rapid advances in
electronics and computing.
1.1 Historical Background and Motivation 3

1.1.2 Nuclear Medicine: Gamma Camera, SPECT, and PET

Nuclear medicine was a relative latecomer as a medical specialty, for example, not
having gained this designation until 1971 by the American Medical Association.
Arguably, the first practical nuclear medicine procedure was developed by Saul
Hertz at the Massachusetts General Hospital in the early 1940s: the treatment of
Grave’s disease by radioactive iodine (radioiodine) using a protocol that remains
largely unchanged today [6].
The foundation of nuclear medicine was laid with the discovery of emissions
from certain heavy metals by Henri Becquerel in 1896 and advanced by Pierre Curie
and Marie Curie, the latter of whom coined the term “radioactivity.” They recog-
nized that some of these emissions were similar to Roentgen’s x-rays and these three
received the Nobel Prize in Physics in 1903 for their discoveries. George de Hevesy
is credited with the radiotracer concept, now used in nuclear medicine, by using
radioactivity to track small quantities of materials for plant physiology studies
[7]. Technological advancements after 1930 enabled the controlled production of
synthetic radioactive materials. Ernest Lawrence built the first cyclotron in 1934 at
the University of California in Berkeley [8], and Enrico Fermi completed the
construction of the first nuclear reactor at the University of Chicago in 1942
[9]. Ironically, while both of these technologies were rapidly advanced for the
development of a weapon of mass destruction during the Manhattan Project, they
both remain crucial for the production of radioactive material essential in nuclear
medicine for the diagnosis and treatment of diseases. Although the use of radioactive
substances to study human physiology or treat disease had been tried before, Hertz’s
radioiodine conception was rapidly accepted by the medical community leading to
the seminal work by Samuel Seidlin in 1946 concerning the use of radioiodine in the
treatment of thyroid cancer [10].
While gamma counters provided rough qualitative estimation of radioactive
material within the human body, relative quantitation and mapping was first pro-
vided by images produced from Benedict Cassen’s rectilinear scanner in 1951. This
device made point-by-point measurements of radioactive uptake in, for example, the
anterior plane of a patient lying flat on a table [11]. Hal Anger’s gamma camera
(1958) provided nuclear medicine clinics with a practical means of planar imaging of
radioactive uptake, greatly improving image quality and reducing scan time [12]. By
rotating an Anger camera about a patient, David Kuhl used the tomographic princi-
ple to image the three-dimensional distribution of radiotracers within a body in a
process now known as SPECT (single photon emission computed tomography)
[13]. Michael Phelps had previously used this tomographic concept on the coinci-
dence detection of pairs of high-energy photons produced by positron emitters
giving positron emission tomography (PET) images with clinically higher-quality
images than SPECT for many applications [14].
4 1 Introduction

Hybrid scanners, enabling the imaging of physiology combining nuclear medi-

cine techniques and anatomy from radiological techniques like CT, are now common
in clinics. This is typically accomplished using united coaxial back-to-back scanners.
The anatomical information can be used to provide improved localization for the
radiotracer uptake or to correct image artifacts caused by the attenuation of emission
photons in SPECT or PET. In the 1990s, SPECT/CT was pioneered by Bruce
Hasegawa [15], and PET/CT was developed by David Townsend [16]. These
devices became commercially available around the turn of the millennium. Current
developments include organ-specific cameras [17], solid-state detection, hybridiza-
tion with magnetic resonance (MR-PET) imaging [18], and sophisticated computer
hardware and software advances that greatly improve diagnostic image quality.

1.1.3 Ultrasound

The military arena has also contributed to the development of ultrasonic imaging.
During World War I, the SONAR (Sound Navigation and Ranging) system was
developed in order to detect underwater submarines. The first ultrasonic imaging
system was probably introduced by Dussik [19] in 1942. He used through-
transmission waves. Ironically, this system attempted to image the brain, a task
which has remained a challenge to this very day for ultrasound.
Many related technical developments contributed to the progress of ultrasonic
imaging in the years that followed. Some noteworthy works are that of George
Ludwig, who used the pulse echo technique (known now as A-mode scanning) to
examine animal tissues (his works were considered classified until 1949). John
Julian Wild and John Reid were probably the first to build an ultrasonic scanner
that produced real-time images (called B-scan) of the breast in 1953 [19]. Ultrasonic
Doppler techniques for medical application were implemented by Shigeo Satomura
and Yasuhara Nimura in 1955 for the study of cardiac valvular motion and pulsa-
tions of peripheral blood vessels [19]. George Kossoff et al. developed phased-array
transducers in 1974. James J Greenleaf et al. were the first to introduce in 1974 an
ultrasonic computed tomography (UCT) system [20]. The use of ultrasound for
evaluating the elastic properties of tissues was suggested by Ophir et al. in 1991
[21, 22]. This has created a new diagnostic field titled “elastography.” A major
development was more recently established by a group including Mathias Fink and
colleagues. They have implemented a planar imaging technique which can provide
images with a rate of several thousand images per second [23]. The combination of
ultrasonic imaging with laser has led to the development of “optoacoustic” imaging,
where excitation of the tissue by a strong laser beam produces sound waves which
are detectible and from which an image can be generated [24]. Ultrasonic imaging is
still continuously progressing along with the general progress achieved in the fields
of electronics and computer science.
1.1 Historical Background and Motivation 5

1.1.4 MRI

The first measurement based on the nuclear magnetic resonance (NMR) phenomena
(see Chap. 6) is attributed to Isidor Rabi in 1938, who received in 1944 the Nobel
Prize in Physics for his work. His research was followed by the work of Felix Bloch
and Edward Purcell (Nobel Prize in Physics 1952), whose research on NMR paved
the road for the development of magnetic resonance imaging (MRI) [25].
Although Raymond V. Damadian was probably the first inventor of the MRI
scanner (received a patent on 1974), he was not awarded the Nobel Prize. The prize
was awarded instead to Paul Lauterbur and Peter Mansfield in 2003. This created a
controversy in the scientific community and outside of it as well [26]. Regardless of
this issue, the first MR image was produced by Paul Lauterbur in 1973. He used
reconstruction algorithms similar to those implemented in CT (such as back projec-
tion methods and iterative reconstruction techniques (see Chap. 2)). In 1975 Richard
Ernst proposed the use of phase and frequency encoding and the Fourier transform
[27] which revolutionized the acquisition and reconstruction methodology of MR
imaging. The first MR image in a living human was produced on July 3, 1977, by
Damadian and colleagues.
The field of MRI has grown exponentially since then with continuous improve-
ments. The progress is both in terms of hardware with scanners having higher
magnetic fields, better gradients, and better coils to improve image acquisition
quality and in software with pulse sequencing to generate better images and establish
new contrast sources. Some notable improvements (among numerous others) are the
development of echo planar imaging (EPI) by Peter Mansfield et al. [28]. This fast
imaging technique enabled functional MR imaging of the living brain and provided a
basis for a new branch of MRI called functional MRI (fMRI). Also, the introduction
of diffusion imaging by Le Bihan et al. [29] in 1985, the first parallel imaging by
Daniel Sodickson et al. [30] in 1997, and the introduction of compressed sensing to
MR image reconstruction by Michael Lustig et al. [31] in 2006 are some notable
contributions made to this field.
MRI is a fascinating field which is probably the most interdisciplinary imaging
modality combining physics, mathematics, engineering, computer science, and of
course medicine. It is considered hazardless and extremely versatile with numerous
methods of distinguishing tissues with details down to the millimeter scale and with
very-high-quality images. However, it is still rather expensive, slow, and cumber-
some in terms of patient handling and accessibility for frequent clinical use.

1.1.5 Other Imaging Modalities

Apart from the major imaging modalities listed above, there was, and still is, a
continuous research effort to expand the field. Some ideas were eventually devel-
oped into clinical tools, and many are still considered immature for practical daily