Description
Book SynopsisMagnetic Resonance Imaging in Tissue Engineering provides a unique overview of the field of non-invasive MRI assessment of tissue engineering and regenerative medicine Establish a dialogue between the tissue-engineering scientists and imaging experts and serves as a guide for tissue engineers and biomaterial developers alikeProvides comprehensive details of magnetic resonance imaging (MRI) techniques used to assess a variety of engineered and regenerating tissues and organsCovers cell-based therapies, engineered cartilage, bone, meniscus, tendon, ligaments, cardiovascular, liver and bladder tissue engineering and regeneration assessed by MRIIncludes a chapter on oxygen imaging method that predominantly is used for assessing hypoxia in solid tumors for improving radiation therapy but has the ability to provide information on design strategies and cellular viability in tissue engineering regenerative medicine
Table of ContentsList 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 X‐Nuclei 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 Super‐Resolution 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 ωQ and ω0τc 54
3.4 Assessment of Tissue‐Engineered 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 (ωQ) 64
3.5.3 Motional Averaging Parameter (ω0τc) 64
3.6 Future Directions 64
3.7 Summary 64
References 65
4 SPIO‐Labeled 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 SPIO‐Labeled Cellular MRI 76
4.3.2 SPIO‐Labeled Cellular MRI in Tissue Engineering 76
4.4 Case Study: SPIO‐Labeled 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 Finite‐Element 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 Tissue‐Specific Applications of Magnetic Resonance Imaging in Tissue Engineering 149
8 Tissue‐Engineered 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 Tissue‐Engineered Cartilage 187
9.7 Periodic Assessment of Tissue‐Engineered 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 Tissue‐Engineered 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 Measure of Success Using NMR/MRI 273
Haakil Lee, Rex M. Jeffries, Andrey P. Tikunov, and Jeffrey M. Macdonald
13.1 Introduction 273
13.2 MRS and MRI Compatibilization—Building Compact RF MR Probes for BALs 278
13.3 Multinuclear MRS of a Hybrid Hollow Fiber–Microcarrier BAL 280
13.3.1 Viability by 31P MRS 282
13.3.2 Quantifying Drug Metabolic Activity and Oxygen Distribution by 19F MRS 284
13.4 1H MRI of a Hollow Fiber Multicoaxial BAL 286
13.4.1 BAL Integrity and Quality Assurance 286
13.4.2 Inoculation Efficiency and Prototype Redesign Iteration 288
13.4.3 Flow Dynamics 289
13.4.4 Diffusion‐Weighted and Functional Annotation Screening Technology (FAST) Dynamic Contrast MRI 291
13.5 Magnetic Contrast Agents Used in MRI of Liver Stem Cell Therapy 293
13.6 31P and 13C MRS of a Fluidized‐Bed BAL Containing Encapsulated Hepatocytes 294
13.6.1 31P MRS Resolution, SNR, Viability, and pH 296
13.6.2 13C MRS to Monitor Real‐Time Metabolism 296
13.7 Future Studies 298
13.7.1 Dynamic Nuclear Polarization 298
13.7.2 Constructing Artificial Organs 300
13.8 Discussion 301
Acknowledgment 303
References 303
14 MRI of Vascularized Tissue‐Engineered Organs 311
Hai‐Ling Margaret Cheng
14.1 Introduction 311
14.2 Importance of Vascularization in Tissue Engineering 312
14.3 Vessel Formation and Maturation: Implications for Imaging 314
14.4 Imaging Approaches to Assess Vascularization 317
14.5 Dynamic Contrast‐Enhanced MRI for Imaging Vascular Physiology 318
14.6 Complementary MRI Techniques to Study Vascularization 321
14.7 Considerations for Preclinical Models and Translation to Clinical Implementation 325
14.8 Future Directions 326
14.9 Conclusions 327
References 327
15 MRI Tools for Assessment of Cardiovascular Tissue Engineering 333
Laurence H. Jackson, Mark F. Lythgoe, and Daniel J. Stuckey
15.1 The Heart and Heart Failure 333
15.2 Cardiac Engineering and Cell Therapy 334
15.3 Imaging Heart Failure 336
15.3.1 Cine MRI 336
15.3.2 Regional Heart Function 338
15.3.3 Viability Imaging 340
15.3.4 Relaxometry and Parametric Imaging 342
15.3.5 Myocardial Perfusion Imaging 344
15.4 Imaging Cardiac Regeneration 346
15.5 Monitoring Cardiac Regeneration 348
15.5.1 MRI to Track Stem Cells 348
15.5.2 MRI to Track Engineered Tissues 353
15.6 Translational Potential and Future Directions 355
References 357
16 Peripheral Nerve Tissue Engineering and Regeneration Observed Using MRI 367
Shan‐Ho Chan and Shan‐hui Hsu
16.1 Introduction 367
16.2 Receiver Coils Commonly Applied in Nerve Tissue Engineering 368
16.3 Various Tools for Real‐Time Monitoring of the Nerve Regeneration 368
16.4 Current Materials, Methods, and Concepts in Peripheral Nerve Repair 368
16.5 MRI Parameters in Peripheral Nerve Tissue Engineering 371
16.6 Advantages of Real‐Time Monitoring of Nerve Regeneration Using MRI 373
16.7 Choosing Animal Models for MRI Studies of Peripheral Nerve Tissue Engineering 374
16.8 Imaging Ability Through Nerve Conduits of Peripheral Nerve Tissue Engineering 375
16.9 Further Imaging Functions of MRI in Peripheral Nerve Tissue Engineering 376
16.10 Tractography in Peripheral Nerve Tissue Engineering 376
16.11 Novel Contrast Agents 378
16.12 Conclusions 378
References 379
Index 383
