This book is written by Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, focusing on tumor boundary, evolution mechanism, imaging technology, probes and equipment, and summarizing relevant scientific and technological papers at home and abroad over the years. This book is mainly divided into six chapters. The first chapter introduces the concept and significance of boundaries, as well as the biomedical aspects of biological boundaries and tumor boundaries; Chapter 2 introduces the tumor boundary and its evolution mechanism, including tumor cell interaction and information transmission, tumor microenvironment analysis, tumor infiltration and distant metastasis mechanisms, etc; Chapters 3 to 5 introduce tumor boundary imaging technologies such as magnetism, optics, and acoustics, imaging probes, imaging equipment, and algorithms. They systematically explain the imaging principles, performance, and practical applications; Chapter 6 summarizes and look

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1994.09-1998.07 南昌大学，分析化学，学士 1998.09-2003.12 中国科学院长春应用化学研究所，电分析化学，博士2004.02-2005.05 德国马尔堡大学，博士后 2005.05-2006.04 美国加州理工学院，博士后 2006.05-2009.06 美国西北大学，助理研究员 2009.06-至 今 中国科学院宁波材料技术与工程研究所，研究员 2015.01-2016.01 德国马尔堡大学，访问教授化学生物学国家杰出青年科学基金 中国分析测试协会科学技术奖特等奖（2014，排名第2）

Contents
Foreword
Preface
CHAPTER 1 Boundaries in Biomedicine 1
1.1 Concept and Significance of Boundaries 1
1.2 Boundaries in Biomedicine 3
1.2.1 Scales in Boundaries in Biomedicine 4
1.2.2 Future Development of Boundaries in Biomedicine 9
1.3 Tumor Boundaries 13
1.3.1 Molecular Events in Tumor Boundaries 14
1.3.2 Cellular Boundaries in Tumor Boundaries 16
1.3.3 Tissue Boundaries in Tumor Boundaries 19
1.3.4 Tumor Boundaries 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 T？-Weighted Imaging and T？-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 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 Techniques 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 T？-Weighted Magnetic Resonance Imaging Probes for Delineating Tumor Boundaries 154
4.1.2 T？-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