Magnetic Resonance Imaging in Tissue Engineering

MRIGNAYANI KOTECHA is currently a research professor of bioengineering at University of Illinois at Chicago and directs the Biomolecular Magnetic Resonance Spectroscopy and Imaging Laboratory (BMRSI). In this position, she is developing proton and sodium magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) techniques for monitoring the growth of musculoskeletal engineered tissues. Her broad research interests include the application of MRI-based techniques to cell and tissue-based regenerative medicine. RICHARD L. MAGIN is currently a professor of bioengineering at University of Illinois at Chicago and directs the Diagnostic NMR Systems Laboratory, USA. Professor Magin is a fellow of the IEEE and AIMBE and a former editor of Critical Reviews in Biomedical Engineering. In 2012 he was designated a "Distinguished" Professor of Bioengineering at UIC. His research interests focus on the applications of magnetic resonance imaging (MRI) in science and engineering. JEREMY J. MAO is currently professor at Columbia University, USA, and also Edwin S. Robinson Endowed Chair. Dr. Mao's research team has been at Columbia for the past 7 years and made several important discoveries including a cover article in The Lancet. In addition, Dr. Mao's work has been published in Nature Medicine, The Lancet, Cell Stem Cell, JCI, and so on. Altogether Dr. Mao has published over 260 scientific papers and proceedings and written 2 books. Dr. Mao's research has led to over 70 patents and establishment of 2 biotechnology companies. Dr. Mao has received a number of prestigious awards including Yasuda Award and Spanadel Award.

• List of Plates xiiiAbout the Editors xixList of Contributors xxiForeword xxvPreface xxviiBook Summary xxxiPart I Enabling Magnetic Resonance Techniques for Tissue Engineering Applications 11 Stem Cell Tissue Engineering and Regenerative Medicine: Role of Imaging 3Bo Chen, Caleb Liebman, Parisa Rabbani, and Michael Cho1.1 Introduction 31.2 3D Biomimetics 51.3 Assessment of Stem Cell Differentiation and Tissue Development 81.4 Description of Imaging Modalities for Tissue Engineering 81.4.1 Optical Microscopy 91.4.2 Fluorescence Microscopy 91.4.3 Multiphoton Microscopy 111.4.4 Magnetic Resonance Imaging 14Acknowledgments 15References 152 Principles and Applications of Quantitative Parametric MRI in Tissue Engineering 21Mrignayani Kotecha2.1 Introduction 212.2 Basics of MRI 252.2.1 Nuclear Spins 252.2.2 Radio Frequency Pulse Excitation and Relaxation 282.2.3 From MRS to MRI 312.3 MRI Contrasts for Tissue Engineering Applications 322.3.1 Chemical Shift 332.3.2 Relaxation Times—T1 and T2 332.3.3 Water Apparent Diffusion Coefficient 362.3.4 Fractional Anisotropy 372.4 X‐Nuclei MRI for Tissue Engineering Applications 382.5 Preparing Engineered Tissues for MRI Assessment 382.5.1 In Vitro Assessment 382.5.2 In Vivo Assessment 392.6 Limitations of MRI Assessment in Tissue Engineering 392.7 Future Directions 402.7.1 Biomolecular Nuclear Magnetic Resonance 402.7.2 Cell–ECM–Biomaterial Interaction 402.7.3 Quantitative MRI 402.7.4 Standardization of MRI Methods for In Vitro and In Vivo Assessment 402.7.5 Super‐Resolution MRI Techniques 412.7.6 Magnetic Resonance Elastography 412.7.7 Benchtop MRI 412.8 Conclusions 41References 423 High Field Sodium MRS/MRI: Application to Cartilage Tissue Engineering 49Mrignayani Kotecha3.1 Introduction 493.2 Sodium as an MR Probe 503.3 Pulse Sequences 533.3.1 Pulse Sequences for Measuring TSC 533.3.2 TQC Pulse Sequences for Measuring ωQ and ω0τc 543.4 Assessment of Tissue‐Engineered Cartilage 553.4.1 Proteoglycan Assessment 573.4.2 Assessment of Tissue Anisotropy and Molecular Dynamics 603.4.3 Assessment of Osteochondral Tissue Engineering 613.5 Sodium Biomarkers for Engineered Tissue Assessment 633.5.1 Engineered Tissue Sodium Concentration (ETSC) 633.5.2 Average Quadrupolar Coupling (ωQ) 643.5.3 Motional Averaging Parameter (ω0τc) 643.6 Future Directions 643.7 Summary 64References 654 SPIO‐Labeled Cellular MRI in Tissue Engineering: A Case Study in Growing Valvular Tissues 71Elnaz Pour Issa and Sharan Ramaswamy4.1 Setting the Stage: A Clinical Problem Requiring a Tissue Engineering Solution 714.2 SPIO Labeling of Cells 724.2.1 Ferumoxides 724.2.2 Transfection Agents 734.2.3 Labeling Protocols 754.3 Applications 764.3.1 Traditional Usage of SPIO‐Labeled Cellular MRI 764.3.2 SPIO‐Labeled Cellular MRI in Tissue Engineering 764.4 Case Study: SPIO‐Labeled Cellular MRI for Heart Valve Tissue Engineering 774.4.1 Experimental Design 774.4.2 Potential Approaches—In Vitro 784.4.3 Potential Approaches—In Vivo 814.5 Conclusions and Future Outlook 83Acknowledgment 84References 845 Magnetic Resonance Elastography Applications in Tissue Engineering 91Shadi F. Othman and Richard L. Magin5.1 Introduction 915.2 Introduction to MRE 935.2.1 Theoretical Basis of MRE 945.2.2 The Inverse Problem and Direct Algebraic Inversion 965.2.3 Direct Algebraic Inversion Algorithm 1015.3 Current Applications of MRE in Tissue Engineering and Regenerative Medicine 1085.3.1 In Vitro TE μMRE 1085.3.2 In Vivo TE μMRE 1105.4 Conclusion 114References 1146 Finite‐Element Method in MR Elastography: Application in Tissue Engineering 117Yifei Liu and Thomas J. Royston6.1 Introduction 1176.2 FEA in MRE Inversion Algorithm Verification 1186.3 FEM in Stiffness Estimation from MRE Data 1206.4 FEA in Experimental Validation in Tissue Engineering Application 1216.5 Conclusions and Discussion 124Acknowledgment 125References 1257 In Vivo EPR Oxygen Imaging: A Case for Tissue Engineering 129Boris Epel, Mrignayani Kotecha, and Howard J. Halpern7.1 Introduction 1297.2 History of EPROI 1317.3 Principles of EPR Imaging 1327.4 EPR Oxymetry 1347.5 EPROI Instrumentation and Methodology 1357.5.1 EPR Frequency 1357.5.2 Resonators 1357.5.3 Magnets 1367.5.4 EPR Imagers 1377.6 Spin Probes for Pulse EPR Oxymetry 1387.7 Image Registration 1397.8 Tissue Engineering Applications 1407.8.1 EPROI in Scaffold Design 1407.8.2 EPROI in Tissue Engineering 1427.9 Summary and Future Outlook 142Acknowledgment 142References 143Part II Tissue‐Specific Applications of Magnetic Resonance Imaging in Tissue Engineering 1498 Tissue‐Engineered Grafts for Bone and Meniscus Regeneration and Their Assessment Using MRI 151Hanying Bai, Mo Chen, Yongxing Liu, Qimei Gong, Ling He, Juan Zhong, Guodong Yang, Jinxuan Zheng, Xuguang Nie, Yixiong Zhang, and Jeremy J. Mao8.1 Overview of Tissue Engineering with MRI 1518.2 Assessment of Bone Regeneration by Tissue Engineering with MRI 1528.3 MRI for 3D Modeling and 3D Print Manufacturing in Tissue Engineering 1578.4 Assessment of Menisci Repair and Regeneration by Tissue Engineering with MRI 1618.5 Conclusion 168Acknowledgments 168References 1699 MRI Assessment of Engineered Cartilage Tissue Growth 179Mrignayani Kotecha and Richard L. Magin9.1 Introduction 1799.2 Cartilage 1819.3 Cartilage Tissue Engineering 1829.3.1 Cells 1839.3.1.1 Chondrocytes 1839.3.1.2 Stem Cells 1839.3.2 Biomaterials 1839.3.3 Growth Factors 1849.3.4 Growth Conditions 1849.4 Animal Models in Cartilage Tissue Engineering 1849.5 Tissue Growth Assessment 1869.6 MRI in the Assessment of Tissue‐Engineered Cartilage 1879.7 Periodic Assessment of Tissue‐Engineered Cartilage Using MRI 1879.7.1 Assessment of Tissue Growth In Vitro 1879.7.1.1 Accounting for Scaffold in Tissue Assessment 1919.7.2 Assessment of Tissue Growth In Vivo 1919.7.3 Assessment of Tissue Anisotropy and Dynamics 1939.7.3.1 Assessment of Macromolecule Composition 1949.7.3.2 Assessment of Tissue Anisotropy 1989.8 Summary and Future Directions 199References 20010 Emerging Techniques for Tendon and Ligament MRI 209Braden C. Fleming, Alison M. Biercevicz, Martha M. Murray, Weiguo Li, and Vincent M. Wang10.1 Tendon and Ligament Structure, Function, Injury, and Healing 20910.2 MRI Studies of Tendon and Ligament Healing 21110.3 MRI and Contrast Mechanisms 21910.3.1 Conventional MRI Techniques 21910.3.2 Advanced MR Techniques 22210.4 Significance and Conclusion 228Acknowledgments 228References 22811 MRI of Engineered Dental and Craniofacial Tissues 237Anne George and Sriram Ravindran11.1 Introduction 23711.2 Scaffolds 23811.3 Extracellular Matrix 23811.4 Tissue Regeneration of Dental–Craniofacial Complex 23911.4.1 Advantages of Using ECM Scaffolds with Stem Cells 24011.4.2 Stem Cells 24211.5 MRI in Tissue Engineering and Regeneration 24311.5.1 MRI of Human DPSCs 24311.5.2 MRI of Tissue‐Engineered Osteogenic Scaffolds 24411.5.3 MRI of Chondrogenic Scaffolds with Cells In Vitro 24411.5.4 MRI of Chondrogenic Scaffolds with Cells In Vivo 24511.5.5 MRI Can Differentiate Between Engineered Bone and Engineered Cartilage 24611.5.6 MRI to Assess Angiogenesis 24611.6 Challenges and Future Directions for MRI in Tissue Engineering 246Acknowledgments 247References 24712 Osteochondral Tissue Engineering: Noninvasive Assessment of Tissue Regeneration 251Tyler Stahl, Abeid Anslip, Ling Lei, Nilse Dos Santos, Emmanuel Nwachuku, Thomas DeBerardino, and Syam Nukavarapu12.1 Introduction 25112.2 Osteochondral Tissue Engineering 25212.2.1 Osteochondral Tissue 25212.2.2 Biomaterials/Scaffolds 25212.2.3 Cells 25512.2.4 Growth Factors 25612.3 Clinical Methods for Osteochondral Defect Repair and Assessment 25712.3.1 Diagnostic Modalities 25712.3.2 Treatment Methods 26012.3.2.1 Microfracture 26012.3.2.2 Autografts and Allografts 26012.3.2.3 Tissue Engineering Grafts 26212.4 MRI Assessment of Tissue Engineered Osteochondral Grafts 26212.4.1 In Vitro Assessment 26312.4.2 In Vivo Assessment 26412.5 MRI Assessment Correlation with Histology 26412.6 Conclusions and Challenges 265Acknowledgments 265References 26513 Advanced Liver Tissue Engineering Approaches and Their Measure of Success Using NMR/MRI 273Haakil Lee, Rex M. Jeffries, Andrey P. Tikunov, and Jeffrey M. Macdonald13.1 Introduction 27313.2 MRS and MRI Compatibilization—Building Compact RF MR Probes for BALs 27813.3 Multinuclear MRS of a Hybrid Hollow Fiber–Microcarrier BAL 28013.3.1 Viability by 31P MRS 28213.3.2 Quantifying Drug Metabolic Activity and Oxygen Distribution by 19F MRS 28413.4 1H MRI of a Hollow Fiber Multicoaxial BAL 28613.4.1 BAL Integrity and Quality Assurance 28613.4.2 Inoculation Efficiency and Prototype Redesign Iteration 28813.4.3 Flow Dynamics 28913.4.4 Diffusion‐Weighted and Functional Annotation Screening Technology (FAST) Dynamic Contrast MRI 29113.5 Magnetic Contrast Agents Used in MRI of Liver Stem Cell Therapy 29313.6 31P and 13C MRS of a Fluidized‐Bed BAL Containing Encapsulated Hepatocytes 29413.6.1 31P MRS Resolution, SNR, Viability, and pH 29613.6.2 13C MRS to Monitor Real‐Time Metabolism 29613.7 Future Studies 29813.7.1 Dynamic Nuclear Polarization 29813.7.2 Constructing Artificial Organs 30013.8 Discussion 301Acknowledgment 303References 30314 MRI of Vascularized Tissue‐Engineered Organs 311Hai‐Ling Margaret Cheng14.1 Introduction 31114.2 Importance of Vascularization in Tissue Engineering 31214.3 Vessel Formation and Maturation: Implications for Imaging 31414.4 Imaging Approaches to Assess Vascularization 31714.5 Dynamic Contrast‐Enhanced MRI for Imaging Vascular Physiology 31814.6 Complementary MRI Techniques to Study Vascularization 32114.7 Considerations for Preclinical Models and Translation to Clinical Implementation 32514.8 Future Directions 32614.9 Conclusions 327References 32715 MRI Tools for Assessment of Cardiovascular Tissue Engineering 333Laurence H. Jackson, Mark F. Lythgoe, and Daniel J. Stuckey15.1 The Heart and Heart Failure 33315.2 Cardiac Engineering and Cell Therapy 33415.3 Imaging Heart Failure 33615.3.1 Cine MRI 33615.3.2 Regional Heart Function 33815.3.3 Viability Imaging 34015.3.4 Relaxometry and Parametric Imaging 34215.3.5 Myocardial Perfusion Imaging 34415.4 Imaging Cardiac Regeneration 34615.5 Monitoring Cardiac Regeneration 34815.5.1 MRI to Track Stem Cells 34815.5.2 MRI to Track Engineered Tissues 35315.6 Translational Potential and Future Directions 355References 35716 Peripheral Nerve Tissue Engineering and Regeneration Observed Using MRI 367Shan‐Ho Chan and Shan‐hui Hsu16.1 Introduction 36716.2 Receiver Coils Commonly Applied in Nerve Tissue Engineering 36816.3 Various Tools for Real‐Time Monitoring of the Nerve Regeneration 36816.4 Current Materials, Methods, and Concepts in Peripheral Nerve Repair 36816.5 MRI Parameters in Peripheral Nerve Tissue Engineering 37116.6 Advantages of Real‐Time Monitoring of Nerve Regeneration Using MRI 37316.7 Choosing Animal Models for MRI Studies of Peripheral Nerve Tissue Engineering 37416.8 Imaging Ability Through Nerve Conduits of Peripheral Nerve Tissue Engineering 37516.9 Further Imaging Functions of MRI in Peripheral Nerve Tissue Engineering 37616.10 Tractography in Peripheral Nerve Tissue Engineering 37616.11 Novel Contrast Agents 37816.12 Conclusions 378References 379Index 383