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List of Plates xiii About the Editors xix List of Contributors xxi Foreword xxv Preface xxvii Book Summary xxxi
Part I Enabling Magnetic Resonance Techniques for Tissue Engineering Applications 1 1 Stem Cell Tissue Engineering and Regenerative Medicine: Role of Imaging 3 Bo Chen, Caleb Liebman, Parisa Rabbani, and Michael Cho
1.1 Introduction 3
1.2 3D Biomimetics 5
1.3 Assessment of Stem Cell Differentiation and Tissue Development 8
1.4 Description of Imaging Modalities for Tissue Engineering 8
1.4.1 Optical Microscopy 9
1.4.2 Fluorescence Microscopy 9
1.4.3 Multiphoton Microscopy 11
1.4.4 Magnetic Resonance Imaging 14 Acknowledgments 15 References 15 2 Principles and Applications of Quantitative Parametric MRI in Tissue Engineering 21 Mrignayani Kotecha
2.1 Introduction 21
2.2 Basics of MRI 25
2.2.1 Nuclear Spins 25
2.2.2 Radio Frequency Pulse Excitation and Relaxation 28
2.2.3 From MRS to MRI 31
2.3 MRI Contrasts for Tissue Engineering Applications 32
2.3.1 Chemical Shift 33
2.3.2 Relaxation Times--T1 and T2 33
2.3.3 Water Apparent Diffusion Coefficient 36
2.3.4 Fractional Anisotropy 37
2.4 XNuclei MRI for Tissue Engineering Applications 38
2.5 Preparing Engineered Tissues for MRI Assessment 38
2.5.1 In Vitro Assessment 38
2.5.2 In Vivo Assessment 39
2.6 Limitations of MRI Assessment in Tissue Engineering 39
2.7 Future Directions 40
2.7.1 Biomolecular Nuclear Magnetic Resonance 40
2.7.2 Cell-ECM-Biomaterial Interaction 40
2.7.3 Quantitative MRI 40
2.7.4 Standardization of MRI Methods for In Vitro and In Vivo Assessment 40
2.7.5 SuperResolution MRI Techniques 41
2.7.6 Magnetic Resonance Elastography 41
2.7.7 Benchtop MRI 41
2.8 Conclusions 41 References 42 3 High Field Sodium MRS/MRI: Application to Cartilage Tissue Engineering 49 Mrignayani Kotecha
3.1 Introduction 49
3.2 Sodium as an MR Probe 50
3.3 Pulse Sequences 53
3.3.1 Pulse Sequences for Measuring TSC 53
3.3.2 TQC Pulse Sequences for Measuring Ï?Q and Ï?0Ï?c 54
3.4 Assessment of TissueEngineered Cartilage 55
3.4.1 Proteoglycan Assessment 57
3.4.2 Assessment of Tissue Anisotropy and Molecular Dynamics 60
3.4.3 Assessment of Osteochondral Tissue Engineering 61
3.5 Sodium Biomarkers for Engineered Tissue Assessment 63
3.5.1 Engineered Tissue Sodium Concentration (ETSC) 63
3.5.2 Average Quadrupolar Coupling (Ï?Q) 64
3.5.3 Motional Averaging Parameter (Ï?0Ï?c) 64
3.6 Future Directions 64
3.7 Summary 64 References 65 4 SPIOLabeled Cellular MRI in Tissue Engineering: A Case Study in Growing Valvular Tissues 71 Elnaz Pour Issa and Sharan Ramaswamy
4.1 Setting the Stage: A Clinical Problem Requiring a Tissue Engineering Solution 71
4.2 SPIO Labeling of Cells 72
4.2.1 Ferumoxides 72
4.2.2 Transfection Agents 73
4.2.3 Labeling Protocols 75
4.3 Applications 76
4.3.1 Traditional Usage of SPIOLabeled Cellular MRI 76
4.3.2 SPIOLabeled Cellular MRI in Tissue Engineering 76
4.4 Case Study: SPIOLabeled Cellular MRI for Heart Valve Tissue Engineering 77
4.4.1 Experimental Design 77
4.4.2 Potential Approaches--In Vitro 78
4.4.3 Potential Approaches--In Vivo 81
4.5 Conclusions and Future Outlook 83 Acknowledgment 84 References 84 5 Magnetic Resonance Elastography Applications in Tissue Engineering 91 Shadi F. Othman and Richard L. Magin
5.1 Introduction 91
5.2 Introduction to MRE 93
5.2.1 Theoretical Basis of MRE 94
5.2.2 The Inverse Problem and Direct Algebraic Inversion 96
5.2.3 Direct Algebraic Inversion Algorithm 101
5.3 Current Applications of MRE in Tissue Engineering and Regenerative Medicine 108
5.3.1 In Vitro TE μMRE 108
5.3.2 In Vivo TE μMRE 110
5.4 Conclusion 114 References 114 6 FiniteElement Method in MR Elastography: Application in Tissue Engineering 117 Yifei Liu and Thomas J. Royston
6.1 Introduction 117
6.2 FEA in MRE Inversion Algorithm Verification 118
6.3 FEM in Stiffness Estimation from MRE Data 120
6.4 FEA in Experimental Validation in Tissue Engineering Application 121
6.5 Conclusions and Discussion 124 Acknowledgment 125 References 125 7 In Vivo EPR Oxygen Imaging: A Case for Tissue Engineering 129 Boris Epel, Mrignayani Kotecha, and Howard J. Halpern
7.1 Introduction 129
7.2 History of EPROI 131
7.3 Principles of EPR Imaging 132
7.4 EPR Oxymetry 134
7.5 EPROI Instrumentation and Methodology 135
7.5.1 EPR Frequency 135
7.5.2 Resonators 135
7.5.3 Magnets 136
7.5.4 EPR Imagers 137
7.6 Spin Probes for Pulse EPR Oxymetry 138
7.7 Image Registration 139
7.8 Tissue Engineering Applications 140
7.8.1 EPROI in Scaffold Design 140
7.8.2 EPROI in Tissue Engineering 142
7.9 Summary and Future Outlook 142 Acknowledgment 142 References 143
Part II TissueSpecific Applications of Magnetic Resonance Imaging in Tissue Engineering 149 8 TissueEngineered Grafts for Bone and Meniscus Regeneration and Their Assessment Using MRI 151 Hanying Bai, Mo Chen, Yongxing Liu, Qimei Gong, Ling He, Juan Zhong, Guodong Yang, Jinxuan Zheng, Xuguang Nie, Yixiong Zhang, and Jeremy J. Mao
8.1 Overview of Tissue Engineering with MRI 151
8.2 Assessment of Bone Regeneration by Tissue Engineering with MRI 152
8.3 MRI for 3D Modeling and 3D Print Manufacturing in Tissue Engineering 157
8.4 Assessment of Menisci Repair and Regeneration by Tissue Engineering with MRI 161
8.5 Conclusion 168 Acknowledgments 168 References 169 9 MRI Assessment of Engineered Cartilage Tissue Growth 179 Mrignayani Kotecha and Richard L. Magin
9.1 Introduction 179
9.2 Cartilage 181
9.3 Cartilage Tissue Engineering 182
9.3.1 Cells 183
9.3.1.1 Chondrocytes 183
9.3.1.2 Stem Cells 183
9.3.2 Biomaterials 183
9.3.3 Growth Factors 184
9.3.4 Growth Conditions 184
9.4 Animal Models in Cartilage Tissue Engineering 184
9.5 Tissue Growth Assessment 186
9.6 MRI in the Assessment of TissueEngineered Cartilage 187
9.7 Periodic Assessment of TissueEngineered Cartilage Using MRI 187
9.7.1 Assessment of Tissue Growth In Vitro 187
9.7.1.1 Accounting for Scaffold in Tissue Assessment 191
9.7.2 Assessment of Tissue Growth In Vivo 191
9.7.3 Assessment of Tissue Anisotropy and Dynamics 193
9.7.3.1 Assessment of Macromolecule Composition 194
9.7.3.2 Assessment of Tissue Anisotropy 198
9.8 Summary and Future Directions 199 References 200 10 Emerging Techniques for Tendon and Ligament MRI 209 Braden C. Fleming, Alison M. Biercevicz, Martha M. Murray, Weiguo Li, and Vincent M. Wang
10.1 Tendon and Ligament Structure, Function, Injury, and Healing 209
10.2 MRI Studies of Tendon and Ligament Healing 211
10.3 MRI and Contrast Mechanisms 219
10.3.1 Conventional MRI Techniques 219
10.3.2 Advanced MR Techniques 222
10.4 Significance and Conclusion 228 Acknowledgments 228 References 228 11 MRI of Engineered Dental and Craniofacial Tissues 237 Anne George and Sriram Ravindran
11.1 Introduction 237
11.2 Scaffolds 238
11.3 Extracellular Matrix 238
11.4 Tissue Regeneration of Dental-Craniofacial Complex 239
11.4.1 Advantages of Using ECM Scaffolds with Stem Cells 240
11.4.2 Stem Cells 242
11.5 MRI in Tissue Engineering and Regeneration 243
11.5.1 MRI of Human DPSCs 243
11.5.2 MRI of TissueEngineered Osteogenic Scaffolds 244
11.5.3 MRI of Chondrogenic Scaffolds with Cells In Vitro 244
11.5.4 MRI of Chondrogenic Scaffolds with Cells In Vivo 245
11.5.5 MRI Can Differentiate Between Engineered Bone and Engineered Cartilage 246
11.5.6 MRI to Assess Angiogenesis 246
11.6 Challenges and Future Directions for MRI in Tissue Engineering 246 Acknowledgments 247 References 247 12 Osteochondral Tissue Engineering: Noninvasive Assessment of Tissue Regeneration 251 Tyler Stahl, Abeid Anslip, Ling Lei, Nilse Dos Santos, Emmanuel Nwachuku, Thomas DeBerardino, and Syam Nukavarapu
12.1 Introduction 251
12.2 Osteochondral Tissue Engineering 252
12.2.1 Osteochondral Tissue 252
12.2.2 Biomaterials/Scaffolds 252
12.2.3 Cells 255
12.2.4 Growth Factors 256
12.3 Clinical Methods for Osteochondral Defect Repair and Assessment 257
12.3.1 Diagnostic Modalities 257
12.3.2 Treatment Methods 260
12.3.2.1 Microfracture 260
12.3.2.2 Autografts and Allografts 260
12.3.2.3 Tissue Engineering Grafts 262
12.4 MRI Assessment of Tissue Engineered Osteochondral Grafts 262
12.4.1 In Vitro Assessment 263
12.4.2 In Vivo Assessment 264
12.5 MRI Assessment Correlation with Histology 264
12.6 Conclusions and Challenges 265 Acknowledgments 265 References 265 13 Advanced Liver Tissue Engineering Approaches and Their Me