分子影像技术及其应用

2012-10  

浙江大学出版社  

田捷  

699  

1382000  

Preface As an effective information acquisition and processing methodology for biomedical study, molecular imaging has become a rapidly developing and very promising research area, in which conventional medical imaging technology and modern molecular biology are being combined to non-invasively delineate in vivo physiological and pathological processes directly, sensitively and specifically at cellular and molecular levels. The goals of this discipline are to develop imaging theories, technologies and instruments for studying biological and medical processes as well as diagnosing and managing diseases better, especially for tumorigenesis research, cancer diagnosis, metastasis detection, gene therapy, drug discovery and development. Discussing the problems and challenges in details and illustrating recent progress and future directions, this book introduces novel theories and algorithms, new molecular probes, imaging systems and experiments, final clinical or preclinical applications of recent years according to the traditional research guidelines from the theory, to the system to be probed and then to the application. This book is based on the published research results of our group and other scholars or experts in the area of molecular imaging. The contents can be divided into three sections. The first section presents the details of molecular imaging theory and the system for different modalities, including diffuse optical tomography (DOT), fluorescence molecular tomography (FMT), bioluminescence tomography (BLT), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI) and some other imaging technologies. For optical molecular imaging, the molecular optical simulation environment (MOSE) is presented for the simulation of light propagation both in tissues with complicated shapes and in free-space based on the Monte Carlo method. Furthermore, optical multi-modality molecular imaging, the algorithms and platforms of medical image processing and analysis are also described in this section. The next section starts with radiolabeled molecular probes and then covers oligonucleotide probes, quantum dots, and RGD-based molecular probes. The last section mainly illustrates the applications of molecular imaging in biomedical and life science research, such as clinical practice for tumors, protein-protein interactions, transgenic animals and diabetes-related studies. This book is supported by the National Basic Research Program of China (973 Program) under Grant Nos. 2006CB705700, 2011CB707700 and the Hundred Talents Program of the Chinese Academy of Sciences. In Part I we are grateful to Professor Jing Bai and her group for Chapter 4 and part of Chapter 10; Professor Shanglian Bao and his group for Chapters 7, 8 and part of Chapter 10; Professor Feng Gao and his group who contributed to Chapter 3; Professor Baoci Shan and his group for providing Chapter 6. We appreciate Professor Taiwei Chu, Professor Deming Kong, Professor Wenyou Li, Professor Fan Wang and their groups for writing Chapters 1, 2, 3 and 4 in Part II, respectively. In Part III we are thankful to Professor Yinghui Li and her group for Chapters 1 and 4; Professor Xiaopeng Zhang and his group for writing Chapter 2; Professor Liangyi Chen and his group for Chapters 3 and 5. Finally, we wish to thank our group, Dr. Karen von Deneen, Dr. Xin Yang, Dr. Chenghu Qin, Dr. Xiaochao Qu, Dr. Shouping Zhu and our students Ping Wu, Jinchao Feng, Kai Liu, Jianghong Zhong, Dong Han, Xibo Ma, Xiaoqian Dai, Xiuli Li, Kexin Deng, Dehui Xiang, Xing Zhang, Wei Jiang, Peng Zhao, Fei Yang and others for editing the text and proof-reading the book. We express our sincere thanks to all the authors for making this book possible and successful.Jie TianBeijing, ChinaJune 8, 2012

　　Jie Tian Editor《Molecular Imaging》 Fundamentals and
Applications is a comprehen-sive monograph which describes not only
the theory of the under-lying algorithms and key technologies but
also introduces a prototype system and its applications，bringing
together theory,technology and applications．

Contents 9
List of Contributors 15
Part I Molecular ImaginPart I Molecular Imaging Theory and
System
1 Introduction
1．1 Development ofMolecular Imaging
1．2 Advantages ofMolecular Imaging
1．3 Basic Pfinciples ofMolecular Imaging Modalities
1．4 Generous Development ofMolecular Imaging Probe
1．5 Application Involving Molecular Imaging
References
2 Molecular Optical Simulation Environment
2．1 Introduction
2．2 Review ofthe Current Simulation PlatforlTl
2．3 Introduction 0fMOSE
2．4 Introduction ofthe Algorithm
2．5 Validation ofthe Simulation Experiment Results．
References
3 Diffuse Optical Tomography
3．1 Outline
3．2 Medical Background and Optical Properties of Human Tissue
3．3 Photon Transport Model in Tissues and Image
Reconstruction
Algorithms
3．4 Simulative and Experimental Tomographic and Topographic
Imaging on a Phantom
References
4 Fluorescence Molecular Tomography
4．1 Overview
4．2 Fundamental Principles in Fluorescence Molecular
Tomography
4．3 Experimental System in Fluorescence Molecular Tomography．
4．4 The Reconstruction Algorithms in Fluorescence Molecular
Tomography
4．5 Experiment in Fluorescence Molecular Tomography
References
5 Bioluminescenee Tomography
5．I Introduction
5．2 The Forward Model for BLT
5．3 BLT Reconstruction Algorithms
5．4 Experiments and Applications
References
6 Positron Emission Tomography
6．1 Prologue
6．2 The Principle ofPET
6．3 Positron Emission Tomography Scanner
6．4 Reconstruction Algorithms and Correction Techniques in
PET
6．5 PET／CT Image Fusion
6．6 Experimental PET Imaging References
7 Radioisotope Labeled Molecular Imaging in SPECT
7．1 Outline ofMolecular Imaging in SPECT
7．2 Key Technologies ofAnimal Pinhole SPECT References
8 MRI Facility-Based Molecular Imaging．
8．1 Outline ofthe MIU Facility—Based Molecular Imaging
8．2 Main mMgI Contrasts．
References．
9 Other Molecular Imaging Technology
9．1 Photoacoustic Tomography
9．2 Optical Coherence Tomography
9．3 Confocal Laser Scanning Microscopy．
9．4 Ultrasound in Molecular Imaging．
9．5 X—Ray Micro-Computed Tomography．
References．
10 Optical Multi-Modality Molecular Imaging
10．1 Fusion ofBLT and Nicro-CT System
10．2 Fusion ofDOT and BLT Systems
10．3 Multi—Mod~ity Imaging ofFMT and CT
10．4 Image Registration and Fusion Between SPECT and CT．
References
11 Medical Image Processing and Analysis
11．1 Overview．
11．2 Medical Image Segmentation
11．3 Medical Image Registration
11．4 New Techniques ofImage Fusion
11．5 Medical Image Visualization．
Reference
PartII Molecular Probes
12 Opportunities and Challenges of Radiolabeled Molecular
Probes
12．1 Introduction
12．2 The Opportunities ofRadiolabeled Molecular Probes．
12．3 The Challenges ofRadiolabeled Molecular Probes
12．4 Summary．
References
13 oli20nucleotide Probes
13．1 Design Principle ofOligonucleotide Probes
13．2 Anti．Nuclease Modification ofOligonucleotide Probes
13．3 Delivery ofProbes into Cells
References
14 Quantum Dots for Biological Imaging
14．1 ODs Based on CdTe
14．2 ODs Based on CdSe
14．3 ODs Based on CdSe／ZnS
14．4 QDs Based on CdSe／CdS／ZnS
14．5 0Ds Based on InP／ZnS
14．6 QDs Based on CdHgTe
14．7 ODs Based on Lead Salts
14．8 Other QDs
References
15 RGD-Based Molecular Probes for Integr in αvβ3Imaging
15．1 Introduction
15．2 Multi—Modality RGD Probes Targeting Integrin αvβ3
15．3 Dual Functional RGD Probes for Integrin αvβ3 Targeting．
15．4 Optimizmion OfRGD Probes
15．5 Conclusions and Future Perspectives
References
Part III Applications of Molecular Imaging．
16 Basics of Molecular Biology
16．1 Introduction．
16．2 Techniques ofMolecular Biology．
16．3 Cells and Viruses
16．4 Transcription
16．5 Transcription and Translation in Eukaryotes
16．6 Post．Transcriptional Events
16．7 DNA Replication and Recombination
16．8 DNA Damage and Repair
16．9 Transiation
References．
17 Molecular Imaging Techniques in Clinical Practice of
Tumors
17．1 Application of Molecular Imaging Techniques in Tumor
Diagnosis and Differentiation
17．2 Application of Molecular Imaging Techniques in the
Clinical
Staging ofMalignancies
17．3 Application ofMolecular Imaging Techniques in Lymph
Nodes
Evaluation
17．4 Application of Molecular Imaging Techniques in Tumor
Therapeutic Monitoring and Efficacy Evaluation
17．5 Application ofMolecular Imaging Techniques in Other
Aspects
ofCancer Therapy
17．6 Conclusions and Prospects．
References
18 Using Molecular Imaging Techniques to Study
Protein-Protein
Interactions．
18．1 The Yeast Two—Hybrid System．
18．2 FRET
18．3 BRET
18．4 PCA
18．5 Concluding Remarks
References
19 Application of Molecular Imaging in Transgenic Animals
19．1 The Stem Cells
19．2 Molecular Imaging in Stem Cell Research for Heart Repair
19．3 Molecular Imaging in Stem Cell Research for Kidney
Repair
19．4 Molecular Imaging in Stem Cell Research for Liver Repair
19．5 Molecular Imaging in Neural Stem Cell Research
19．6 Conclusion
References．
20 Molecular Imaging Methods in Diabetes-Related Studies
20．1 Molecular Imaging Applications in Diabetes—Related
Fundamental
Research
20．2 Molecular Imaging Assists Diabetic—Related Therapeutic
Research
20．3 Recent Advances in Molecular Imaging．
20．4 Concluding Remarks
References
Index g Theory and System 18
1　Introduction 20
1.1 Development of Molecular Imaging 20
1.2 Advantages of Molecular Imaging 22
1.3 Basic Principles of Molecular Imaging Modalities 24
1.4 Generous Development of Molecular Imaging Probe 27
1.5 Application Involving Molecular Imaging 28
References 29
2　Molecular Optical Simulation Environment 32
2.1 Introduction 32
2.2 Review of the Current Simulation Platform 33
2.3 Introduction of MOSE 35
2.4 Introduction of the Algorithm 44
2.5 Validation of the Simulation Experiment Results 57
References 62
3　Diffuse Optical Tomography 64
3.1 Outline 64
3.2 Medical Background and Optical Properties of HumanTissue
94
3.3 Photon Transport Model in Tissues and Image
ReconstructionAlgorithms 110
3.4 Simulative and Experimental Tomographic and TopographicImaging
on a Phantom 153
References 193
4　Fluorescence Molecular Tomography 202
4.1 Overview 202
4.2 Fundamental Principles in Fluorescence Molecular Tomography
203
4.3 Experimental System in Fluorescence Molecular Tomography
206
4.4 The Reconstruction Algorithms in Fluorescence
MolecularTomography 208
4.5 Experiment in Fluorescence Molecular Tomography 218
References 228
5　Bioluminescence Tomography 234
5.1 Introduction 234
5.2 The Forward Model for BLT 236
5.3 BLT Reconstruction Algorithms 238
5.4 Experiments and Applications 250
References 255
6　Positron Emission Tomography 258
6.1 Prologue 258
6.2 The Principle of PET 260
6.3 Positron Emission Tomography Scanner 263
6.4 Reconstruction Algorithms and Correction Techniques inPET
272
6.5 PET/CT Image Fusion 306
6.6 Experimental PET Imaging 313
References 320
7　Radioisotope Labeled Molecular Imaging inSPECT 330
7.1 Outline of Molecular Imaging in SPECT 330
7.2 Key Technologies of Animal Pinhole SPECT 336
References 347
8　MRI Facility-Based Molecular Imaging 350
8.1 Outline of the MRI Facility-Based Molecular Imaging 350
8.2 Main mMRI Contrasts 354
References 376
9　Other Molecular Imaging Technology 378
9.1 Photoacoustic Tomography 378
9.2 Optical Coherence Tomography 384
9.3 Confocal Laser Scanning Microscopy 389
9.4 Ultrasound in Molecular Imaging 392
9.5 X-Ray Micro-Computed Tomography 395
References 399
10　Optical Multi-Modality Molecular Imaging 406
10.1 Fusion of BLT and Nicro-CT System 407
10.2 Fusion of DOT and BLT Systems 410
10.3 Multi-Modality Imaging of FMT and CT 412
10.4 Image Registration and Fusion Between SPECT and CT 417
References 427
11　Medical Image Processing and Analysis 432
11.1 Overview 432
11.2 Medical Image Segmentation 433
11.3 Medical Image Registration 440
11.4 New Techniques of Image Fusion 456
11.5 Medical Image Visualization 472
References 483
Part II Molecular Probes 488
12　Opportunities and Challenges of RadiolabeledMolecular Probes
490
12.1 Introduction 490
12.2 The Opportunities of Radiolabeled Molecular Probes 491
12.3 The Challenges of Radiolabeled Molecular Probes 493
12.4 Summary 497
References 497
13　Oligonucleotide Probes 500
13.1 Design Principle of Oligonucleotide Probes 500
13.2 Anti-Nuclease Modification of Oligonucleotide Probes 506
13.3 Delivery of Probes into Cells 508
References 511
14　Quantum Dots for Biological Imaging 518
14.1 QDs Based on CdTe 518
14.2 QDs Based on CdSe 519
14.3 QDs Based on CdSe/ZnS 520
14.4 QDs Based on CdSe/CdS/ZnS 520
14.5 QDs Based on InP/ZnS 522
14.6 QDs Based on CdHgTe 522
14.7 QDs Based on Lead Salts 523
14.8 Other QDs 523
References 525
15　RGD-Based Molecular Probes for Integrin αv β3Imaging 530
15.1 Introduction 530
15.2 Multi-Modality RGD Probes Targeting Integrin αv β3 533
15.3 Dual Functional RGD Probes for Integrin αv β3 Targeting
542
15.4 Optimization of RGD Probes 543
15.5 Conclusions and Future Perspectives 549
References 550
Part III Applications of Molecular Imaging 556
16　Basics of Molecular Biology 558
16.1 Introduction 558
16.2 Techniques of Molecular Biology 564
16.3 Cells and Viruses 569
16.4 Transcription 573
16.5 Transcription and Translation in Eukaryotes 576
16.6 Post-Transcriptional Events 585
16.7 DNA Replication and Recombination 590
16.8 DNA Damage and Repair 598
16.9 Translation 607
References 609
17　Molecular Imaging Techniques in Clinical Practiceof Tumors
620
17.1 Application of Molecular Imaging Techniques in TumorDiagnosis
and Differentiation 620
17.2 Application of Molecular Imaging Techniques in theClinical
Staging of Malignancies 625
17.3 Application of Molecular Imaging Techniques in LymphNodes
Evaluation 628
17.4 Application of Molecular Imaging Techniques in
TumorTherapeutic Monitoring and Efficacy Evaluation 633
17.5 Application of Molecular Imaging Techniques in OtherAspects of
Cancer Therapy 636
17.6 Conclusions and Prospects 639
References 639
18　Using Molecular Imaging Techniques to StudyProtein-Protein
Interactions 650
18.1 The Yeast Two-Hybrid System 650
18.2 FRET 656
18.3 BRET 663
18.4 PCA 667
18.5 Concluding Remarks 670
References 671
19　Application of Molecular Imaging in TransgenicAnimals 678
19.1 The Stem Cells 678
19.2 Molecular Imaging in Stem Cell Research for Heart Repair
679
19.3 Molecular Imaging in Stem Cell Research for Kidney Repair
682
19.4 Molecular Imaging in Stem Cell Research for Liver Repair
683
19.5 Molecular Imaging in Neural Stem Cell Research 684
19.6 Conclusion 685
References 685
20　Molecular Imaging Methods in Diabetes-RelatedStudies 688
20.1 Molecular Imaging Applications in Diabetes-RelatedFundamental
Research 689
20.2 Molecular Imaging Assists Diabetic-Related TherapeuticResearch
696
20.3 Recent Advances in Molecular Imaging 704
20.4 Concluding Remarks 706
References 706
Index 712

《中国科技进展丛书:分子影像技术及其应用(英文版)》通过对分子影像学的基本概念、基本原理、成像方法、研究进展和及其在生物制药领域应用的介绍，为从事医学影像研究和生命科学研究的科研人员提供详尽的理论知识和技术方法。《中国科技进展丛书:分子影像技术及其应用(英文版)》既有理论算法，又有关键技术，既有原型系统，又有应用实例，是理论、技术与应用相结合的产物。

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