Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . III
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V
CHAPTER 1
Boundarics in Biomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Concept and Significance of Boundaries . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Boundarics in Biomedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.1 Scales in Boundarics in Biomedicine . . . . . . . . . . . . . . . . . . . . . 4
1.2.2 Future Development of Boundarics in Biomedicine . . . . . . . . . . 9
1.3 Tumor Boundarics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
1.3.1 Molecular Events in Tumor Boundarics . . . . . . . . . . . . . . . . . . 14
1.3.2 Cellular Boundaries in Tumor Boundarics . . . . . . . . . . . . . . . . 16
1.3.3 Tissue Boundaries in Tumor Boundarics. . . . . . . . . . . . . . . . . . 19
1.3.4 Tumor Boundarics In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
CHAPTER 2
Tumor Boundary and Its Evolution Mechanisms . . . . . . . . . . . . . . . . . . . . . . 27
2.1 Early Formation of the Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . 27
2.1.1 Gene Mutation at the Tumor Boundaries . . . . . . . . . . . . . . . . . 27
2.1.2 Epigenetic Changes at the Tumor Boundaries . . . . . . . . . . . . . 31
2.1.3 Heterogeneity at the Tumor Boundaries . . . . . . . . . . . . . . . . . . 34
2.2 Evolution of the Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.2.1 Cellular Interactions and Information Transmission at the Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.2.2 Remodeling of Microenvironment at the Tumor Boundaries . . . 42
2.3 Mechanisms of Tumor Boundary Infiltration and Metastasis . . . . . . . . 50
2.3.1 Mechanism of Tumor Boundary Infiltration . . . . . . . . . . . . . . . 50
2.3.2 Mechanisms of Tumor Metastasis . . . . . . . . . . . . . . . . . . . . . . . 55
2.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
CHAPTER 3
Tumor Boundary Imaging Technologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3.1 Magnetic Imaging Technologies for Tumor Boundaries . . . . . . . . . . . . 69
3.1.1 Magnetic Resonance Spectroscopic Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 70
3.1.2 Chemical Exchange Saturation Transfer Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . 72
3.1.3 Heteronuclear Magnetic Resonance Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 75
3.1.4 Diffusion-Weighted Imaging Technique for Tumor Boundaries . 76
3.1.5 Diffusion Tensor Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.1.6 Dynamic Contrast-Enhanced Magnetic Resonance Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . 79
3.1.7 Functional Magnetic Resonance Imaging Technique for Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
3.1.8 Multi-Parameter Magnetic Resonance Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 82
3.1.9 Contrast-Enhanced Magnetic Resonance Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 84
3.1.10 T1-Weighted Imaging and T2-Weighted Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . 85
3.2 Optical Imaging Technologies for Tumor Boundaries . . . . . . . . . . . . . . 87
3.2.1 Characteristics of Optical Imaging Technologies . . . . . . . . . . . . 87
3.2.2 Principles of Optical Imaging Technologies . . . . . . . . . . . . . . . . 88
3.2.3 Fluorescence and Phosphorescence Imaging Techniques for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 92
3.2.4 Raman Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
3.3 Computed Tomography Imaging Technologies for Tumor Boundaries . 108
3.3.1 Traditional Computed Tomography Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 108
3.3.2 Dual-Energy Computed Tomography Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 111
3.3.3 Single-Photon Emission Computed Tomography Imaging Technique for Delineating of Tumor Boundaries . . . . . 114
3.3.4 Photon-Counting Computed Tomography Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . 115
3.3.5 Phase-Contrast Tomography with Layered Imaging Technique for Delineating of Tumor Boundaries . . . . . 115
3.3.6 AI-Assisted Computed Tomography Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 116
3.4 Acoustic Imaging Technologies for Tumor Boundaries . . . . . . . . . . . . . 119
3.4.1 Ultrasound Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
3.4.2 Super-Resolution Ultrasound Imaging Technique for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 122
3.4.3 Photoacoustic Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
3.4.4 Ultrasound-Excited Optical Imaging Technique for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . 130
3.5 Multimodal Imaging Technologies for Tumor Boundaries. . . . . . . . . . . 132
3.5.1 Principles of Multimodal Imaging Technologies . . . . . . . . . . . . 133
3.5.2 Multimodal Imaging Technologies for Delineation of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
3.5.3 Future Directions for Multimodal Imaging Technologies for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 139
3.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
CHAPTER 4
Tumor Boundary Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
4.1 Magnetic Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
4.1.1 T1-Weighted Magnetic Resonance Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 154
4.1.2 T2-Weighted Magnetic Resonance Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 161
4.1.3 Dual-Modal Magnetic Resonance Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 164
4.1.4 Organic Magnetic Resonance Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
4.2 Optical Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
4.2.1 Fluorescence Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
4.2.2 Phosphorescent Imaging Probes for Delineating of Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
4.2.3 Raman Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
4.3 Acoustic Imaging Probes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
4.3.1 Ultrasound Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
4.3.2 Photoacoustic Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
4.3.3 Acoustic Therapy Visualization Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . 213
4.4 Radionuclide Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
4.4.1 Advantages of Radionuclide Imaging Probes . . . . . . . . . . . . . . 216
4.4.2 Types of Radionuclide Imaging Probes . . . . . . . . . . . . . . . . . . . 217
4.4.3 Radionuclide Imaging Probes for Delineating Tumor Boundaries . . . .. . . 222
4.5 Multimodal Imaging Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
4.5.1 Advantages of Multimodal Imaging Probes . . . . . . . . . . . . . . . 228
4.5.2 Optical and Magnetic Resonance Multimodal Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . 230
4.5.3 Optical Imaging and Positron Emission Tomography Multimodal Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
4.5.4 Magnetic Resonance and X-ray Computed Tomography Multimodal Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
4.5.5 Magnetic Resonance and Photoacoustic Multimodal Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . 244
4.5.6 Magnetic Resonance and Positron Emission Tomography Multimodal Imaging Probes for Delineating Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
4.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
CHAPTER 5
Tumor Boundary Imaging Equipment and Algorithm . . . . . . . . . . . . . . . . . . 263
5.1 Magnetic Resonance Imaging Equipment and Algorithm . . . . . . . . . . . 263
5.1.1 Magnetic Resonance Imaging Equipment . . . . . . . . . . . . . . . . . 264
5.1.2 Magnetic Resonance Imaging Algorithms . . . . . . . . . . . . . . . . . 274
5.1.3 Magnetic Resonance Imaging Algorithms for Tumor Boundaries . . . . . . .. . . . . . . . . 276
5.2 Optical Imaging Equipment and Algorithms . . . . . . . . . . . . . . . . . . . . 286
5.2.1 Super-Resolution Fluorescence Microscopy Imaging Equipment and Algorithms . . . .. . . . 287
5.2.2 Coherent Raman Scattering Microscopy Imaging Equipment and Algorithms . . . . .. . . . . 294
5.2.3 Multiphoton Microscopy Imaging Equipment and Algorithms. . 298
5.2.4 Harmonic Microscopy Imaging Equipment and Algorithms . . . . 302
5.2.5 Near-Infrared In Vivo Fluorescence Imaging Equipment and Algorithms . . . .. . . . 305
5.3 Acoustic Imaging Equipment and Algorithms . . . . . . . . . . . . . . . . . . . 308
5.3.1 Acoustic Imaging Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . 308
5.3.2 Acoustic Imaging Algorithm. . . . . . . . . . . . . . . . . . . . . . . . . . . 319
5.4 Nuclear Medicine Imaging Equipment and Algorithms . . . . . . . . . . . . 329
5.4.1 Nuclear Medicine Imaging Equipment and Algorithms . . . . . . . 330
5.4.2 Nuclear Medicine Imaging Equipment for Delineating
Tumor Boundaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
5.4.3 Nuclear Medicine Imaging Algorithms for Delineating Tumor Boundaries . . . .. . . . . 337
5.5 Multimodal Imaging Equipment and Algorithms . . . . . . . . . . . . . . . . . 343
5.5.1 Multimodal Imaging Equipment . . . . . . . . . . . . . . . . . . . . . . . . 344
5.5.2 Multimodal Imaging Algorithms. . . . . . . . . . . . . . . . . . . . . . . . 351
5.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
CHAPTER 6
Summary and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
6.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
6.1.1 Multidimensional Understanding of Biological Boundaries . . . . 377
6.1.2 Tumor Boundaries in Biomedicine and Key Events
in Boundary Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
6.1.3 Imaging Technologies for Tumor Boundaries . . . . . . . . . . . . . . 378
6.1.4 Imaging Probes for Tumor Boundaries . . . . . . . . . . . . . . . . . . . 379
6.1.5 Imaging Equipment and Algorithms for Tumor Boundaries . . . 379
6.2 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
6.2.1 Future Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
6.2.2 Proposed Solutions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
