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Book Details
Abstract
This unique book describes the latest information in the fundamental understanding of the biophysics and biochemistry of articular cartilage using the state-of-the-art practices in NMR and MRI. This is the first book of its kind, written by physicists and chemists on this important tissue, whose degradation contributes to osteoarthritis and related joint diseases. Connecting the fundamental science with the clinical imaging applications, the experts Editors provide an authoritative addition to the literature.
Ideal for practising physical scientists and radiologists with an interest in the fundamental science as well as instrument manufacturers and clinical researchers working with articular cartilage.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Biophysics and Biochemistry of Cartilage by NMR and MRI | i | ||
| Preface | v | ||
| Acknowledgements | ix | ||
| Contents | xiii | ||
| Part One - Introduction | 1 | ||
| Chapter 1 - Introduction to Cartilage | 3 | ||
| 1.1 Introduction | 3 | ||
| 1.2 Cartilage and the Joint | 4 | ||
| 1.2.1 Different Types of Cartilage | 4 | ||
| 1.2.2 Synovial Joints and Articular Cartilage | 5 | ||
| 1.3 Cellular Aspects of Articular Cartilage | 7 | ||
| 1.3.1 Cartilage Progenitor Cells | 8 | ||
| 1.3.2 Mature Chondrocytes in Cartilage | 8 | ||
| 1.3.3 Mesenchymal Stem Cells | 10 | ||
| 1.4 Extracellular Matrix of Articular Cartilage | 10 | ||
| 1.4.1 Collagen | 11 | ||
| 1.4.2 Proteoglycans and Glycosaminoglycans | 12 | ||
| 1.4.3 Water | 13 | ||
| 1.4.4 Other Components | 15 | ||
| 1.5 Histological Structure of Articular Cartilage | 16 | ||
| 1.5.1 The Zonal Structure of Articular Cartilage | 16 | ||
| 1.5.2 Depth-Dependent Physicochemical Properties | 17 | ||
| 1.6 Biomechanical Properties of Articular Cartilage | 18 | ||
| 1.6.1 The Uncompressed Equilibrium State | 18 | ||
| 1.6.2 Compression of Articular Cartilage | 20 | ||
| 1.7 Joint and Gross Morphology of Articular Cartilage | 25 | ||
| 1.7.1 Development of Synovial Joint | 25 | ||
| 1.7.2 Topographic Distributions in the Knee | 26 | ||
| 1.7.3 Topographic Distributions in the Shoulder | 27 | ||
| 1.7.4 The Split-Line Pattern | 28 | ||
| 1.8 The Diseases of Cartilage and Joints | 29 | ||
| 1.8.1 Classification and Etiology of Osteoarthritis | 29 | ||
| 1.8.2 Pathogenesis | 29 | ||
| 1.8.3 The Role of Subchondral Bone | 30 | ||
| 1.8.4 Biomarkers | 30 | ||
| 1.8.5 Treatment | 31 | ||
| 1.9 Osteoarthritis Research | 31 | ||
| 1.9.1 In vivo Models of Osteoarthritis | 32 | ||
| 1.9.2 In vitro Models of Cartilage Degeneration | 33 | ||
| Acknowledgements | 34 | ||
| References | 35 | ||
| Chapter 2 - Osmotic Properties of Cartilage | 44 | ||
| 2.1 Introduction | 44 | ||
| 2.2 Cartilage Molecular Architecture, Gross Appearance, and Morphology | 46 | ||
| 2.3 Osmotic Swelling Pressure of Cartilage | 48 | ||
| 2.4 Molecular Interactions of Cartilage Polymers | 51 | ||
| 2.4.1 Osmotic Observations | 51 | ||
| 2.4.2 Small-Angle Scattering Measurements | 53 | ||
| 2.4.3 Dynamic Properties of Proteoglycan Assemblies | 55 | ||
| 2.5 Conclusions | 58 | ||
| Acknowledgements | 59 | ||
| References | 59 | ||
| Chapter 3 - Introduction to NMR and MRI | 62 | ||
| 3.1 Introduction | 62 | ||
| 3.2 Semiclassical Description of NMR | 63 | ||
| 3.2.1 NMR-Active Nuclei | 63 | ||
| 3.2.2 Vector Description of NMR | 66 | ||
| 3.2.3 Excitation | 68 | ||
| 3.2.4 Precession and the Bloch Equation | 69 | ||
| 3.2.5 Rotating Frame | 70 | ||
| 3.2.6 Chemical Shielding and Chemical Shift | 71 | ||
| 3.2.7 Spin Relaxation | 73 | ||
| 3.2.8 NMR Signal Detection | 77 | ||
| 3.2.9 Spin Echo and NMR Pulse Sequences | 78 | ||
| 3.3 Quantum Description of NMR | 80 | ||
| 3.3.1 Spin and Angular Momentum | 81 | ||
| 3.3.2 Conceptual Points | 82 | ||
| 3.3.3 Matrix Representation of Spin Operators | 82 | ||
| 3.3.4 Zeeman Hamiltonian | 83 | ||
| 3.3.5 Nuclear Magnetisation | 83 | ||
| 3.3.6 Evolution of the Spin Density Matrix | 85 | ||
| 3.3.7 NMR Observables and Coherence Order | 88 | ||
| 3.3.8 Spin Relaxation | 89 | ||
| 3.3.9 Anisotropic Spin Hamiltonians and NMR Spectra | 91 | ||
| 3.4 MRI | 92 | ||
| 3.4.1 Fourier MRI | 92 | ||
| 3.4.2 Implementation of Fourier Imaging | 95 | ||
| 3.4.3 Image Contrast | 98 | ||
| 3.4.4 Spatial Resolution and the SNR | 99 | ||
| 3.4.5 Parameter Mapping Versus Weighted Imaging | 99 | ||
| 3.5 Conclusion | 100 | ||
| Abbreviations and Symbols | 101 | ||
| Acknowledgements | 101 | ||
| References | 102 | ||
| Chapter 4 - The Magic Angle Effect in NMR and MRI of Cartilage | 109 | ||
| 4.1 Introduction | 109 | ||
| 4.2 Basic Physics and Physical Chemistry | 112 | ||
| 4.2.1 Electronegativity and Partial Charges | 112 | ||
| 4.2.2 Role of Hydrogen Bonds | 112 | ||
| 4.2.3 Protein: Polar Solutes | 113 | ||
| 4.2.4 Bound Water | 114 | ||
| 4.3 Basic Concepts of NMR Relaxation | 115 | ||
| 4.3.1 NMR Spin-Lattice Relaxation and Molecular Motion | 115 | ||
| 4.3.2 Proton Fast Exchange | 117 | ||
| 4.3.3 NMR Titration Study of Protein Solutions | 117 | ||
| 4.3.4 NMR Titration of Native Bovine Tendon | 118 | ||
| 4.3.5 Bound Water Equivalence to Water Bridges | 119 | ||
| 4.3.6 Double Water Bridges | 121 | ||
| 4.4 Formation of a Molecular Model | 122 | ||
| 4.4.1 Stoichiometric Hydration Model | 122 | ||
| 4.4.2 SHM Applied to Collagen | 125 | ||
| 4.4.3 SHM Water Bridge Binding Energy Predictions | 127 | ||
| 4.4.4 Anisotropic Rotation of Water Bridges | 129 | ||
| 4.4.5 Water Bridge Source for Magic Angle Effects | 131 | ||
| 4.4.6 SHM Explanation of Biphasic and Monophasic T2 | 133 | ||
| 4.5 Cartilage and the Magic Angle Effect | 134 | ||
| 4.5.1 Collagen in Cartilage | 134 | ||
| 4.5.2 Magic Angle Effect in Cartilage | 135 | ||
| 4.5.3 Multi-Exponential Versus Mono-Exponential T2 Relaxation | 136 | ||
| 4.6 Revisiting the 1985 Tendon Relaxation Report | 139 | ||
| 4.7 The T2 Versus T2* Conundrum | 139 | ||
| 4.8 Conclusions and Discussion | 141 | ||
| References | 142 | ||
| Part Two - Cartilage Research by Experimental NMR and MRI Techniques | 145 | ||
| Chapter 5 - Physical Properties of Cartilage by Relaxation Anisotropy | 147 | ||
| 5.1 Introduction | 147 | ||
| 5.1.1 Relaxation Anisotropy | 148 | ||
| 5.1.2 Physical Properties of Cartilage | 148 | ||
| 5.1.3 Relaxation Anisotropy in Cartilage | 149 | ||
| 5.1.4 Relaxation Anisotropy in Other Tissues | 150 | ||
| 5.1.5 Theoretical and Simulation Work on Articular Cartilage | 151 | ||
| 5.2 Anisotropy of T2 Relaxation Time in Cartilage | 151 | ||
| 5.2.1 Dependence of T2 Relaxation on Collagen Orientation | 151 | ||
| 5.2.2 Dependence of T2 Relaxation on Collagen Content and Tissue Hydration | 153 | ||
| 5.2.3 Spatial and Topographical Variation of T2 Relaxation Time | 153 | ||
| 5.2.4 T2 Relaxation in Detection of Anisotropy-Related Cartilage Maturation | 154 | ||
| 5.2.5 T2 Relaxation in Detection of Cartilage Repair | 156 | ||
| 5.3 Anisotropy of T1ρ Relaxation in Cartilage | 156 | ||
| 5.4 Different Relaxation Mechanisms in T1ρ | 161 | ||
| 5.5 Anisotropy of T1 Relaxation in Cartilage | 163 | ||
| 5.5.1 Pre-contrast T1 Relaxation Time | 163 | ||
| 5.5.2 Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) | 164 | ||
| 5.6 Sensitivities in Practical Relaxation Measurement | 167 | ||
| 5.7 Conclusions | 168 | ||
| Acknowledgement | 169 | ||
| References | 169 | ||
| Chapter 6 - Chemical Properties of Cartilage Studied Using Charged Ions | 176 | ||
| 6.1 Introduction | 176 | ||
| 6.2 The dGEMRIC Method | 178 | ||
| 6.2.1 The Basis of the dGEMRIC Method | 178 | ||
| 6.2.2 Clinical Applications of dGEMRIC | 186 | ||
| 6.3 Concluding Remarks and Future Prospects | 188 | ||
| References | 189 | ||
| Chapter 7 - Quantification of Articular Cartilage Microstructure by the Analysis of the Diffusion Tensor | 191 | ||
| 7.1 Introduction | 191 | ||
| 7.2 Diffusion Magnetic Resonance | 192 | ||
| 7.2.1 Diffusion NMR Spectroscopy | 193 | ||
| 7.2.2 General Treatment and the Diffusion Propagator | 195 | ||
| 7.2.3 Diffusion Imaging | 196 | ||
| 7.2.3.1 Diffusion Tensor Imaging | 196 | ||
| 7.3 Diffusion Magnetic Resonance of Articular Cartilage | 199 | ||
| 7.4 Diffusion Simulations in Articular Cartilage | 200 | ||
| 7.4.1 Constructing Idealised Fibre Networks | 200 | ||
| 7.4.1.1 Networks of Aligned Cylinders | 201 | ||
| 7.4.1.2 Adding Orientational Disorder | 202 | ||
| 7.4.1.3 Controlling the Fibre Volume Fraction | 203 | ||
| 7.4.1.4 Cross-Linked Fibre Networks | 203 | ||
| 7.4.2 Diffusion of Water in Model Networks | 204 | ||
| 7.4.2.1 Monte Carlo Simulations | 204 | ||
| 7.4.2.2 Langevin Dynamics | 206 | ||
| 7.4.3 Reconstructing the Diffusion Tensor | 208 | ||
| 7.4.4 Simulation Parameters and Considerations | 210 | ||
| 7.4.4.1 Diffusion Coefficient and Implicitly Modelling Proteoglycans | 210 | ||
| 7.4.4.2 Modelling the Long Diffusion Time Limit | 210 | ||
| 7.4.4.3 Simulation Boundary Conditions | 211 | ||
| 7.4.4.4 Artefacts in Disordered Networks and Networks of a Finite Size | 211 | ||
| 7.4.4.5 Simulation Noise and Systematic Errors | 212 | ||
| 7.4.5 Diffusion Trends Through Model Networks | 212 | ||
| 7.4.5.1 Aligned Networks | 213 | ||
| 7.4.5.2 Partially Aligned and Disordered Networks | 215 | ||
| 7.5 Combining Experiments and Simulations | 215 | ||
| 7.6 Post-DTI Approaches to Cartilage Diffusion Imaging | 216 | ||
| 7.7 Conclusions | 218 | ||
| Acknowledgements | 219 | ||
| References | 219 | ||
| Chapter 8 - Sodium and Other Exotic Methods in NMR and MRI of Cartilage | 225 | ||
| 8.1 Clinical Need | 225 | ||
| 8.1.1 Current Methods of Detecting Cartilage Degeneration with Imaging | 226 | ||
| 8.2 Sodium NMR | 227 | ||
| 8.2.1 Sodium MRI of Cartilage | 227 | ||
| 8.2.2 Advantage of Sodium MRI | 227 | ||
| 8.2.3 Limitations of Sodium MRI | 229 | ||
| 8.3 T1ρ MRI | 229 | ||
| 8.3.1 Mechanism of T1ρ Relaxation in Tissues | 231 | ||
| 8.3.2 T1ρ MRI Methods | 231 | ||
| 8.3.3 T1ρ MRI Pulse Sequences | 232 | ||
| 8.3.4 T1ρ MRI as a Biomarker of Cartilage | 235 | ||
| 8.4 Chemical Exchange Saturation Transfer | 238 | ||
| 8.4.1 CEST MRI of Cartilage | 238 | ||
| 8.5 Summary | 240 | ||
| Acknowledgements | 241 | ||
| References | 242 | ||
| Chapter 9 - Multi-Quantum Filtered NMR and MRI of Cartilage | 246 | ||
| 9.1 Introduction | 246 | ||
| 9.2 Theoretical Background | 248 | ||
| 9.3 2H and 23Na DQF NMR of Nasal Cartilage | 253 | ||
| 9.4 Mapping the Orientation of the Collagen Fibers in Articular Cartilage | 256 | ||
| 9.5 The Effect of the Detachment from the Bone | 258 | ||
| 9.6 Comparison of the Effects of Mechanical Load and Osmotic Pressure on Articular Cartilage | 260 | ||
| 9.7 The Effect of Decalcification | 263 | ||
| 9.8 Maturation of Pig Articular Cartilage | 266 | ||
| 9.9 23Na Spectroscopy and Imaging of Intact and Proteoglycan-Depleted Articular Cartilage | 270 | ||
| 9.10 23Na and 2H Studies of Osteoarthritic and Osteoporotic Articular Cartilage | 270 | ||
| 9.11 Sodium Triple Quantum Imaging | 272 | ||
| 9.12 1H DQF Imaging of Connective Tissues | 273 | ||
| 9.13 Conclusions | 275 | ||
| References | 275 | ||
| Chapter 10 - Solid-State NMR Techniques to Study the Molecular Dynamics in Cartilage | 279 | ||
| 10.1 Introduction | 279 | ||
| 10.2 Methodological Concepts of Studying Cartilage by Solid-State NMR Spectroscopy | 281 | ||
| 10.2.1 Static Solid-State NMR Techniques | 281 | ||
| 10.2.2 Magic-Angle Spinning Solid-State NMR Techniques | 284 | ||
| 10.3 Molecular Dynamics of GAGs and Collagen in Cartilage Tissue | 285 | ||
| 10.3.1 GAG Dynamics in Native Cartilage Tissue | 285 | ||
| 10.3.2 Collagen Dynamics in Native Cartilage Tissue | 287 | ||
| 10.4 Hydration of Cartilage | 290 | ||
| 10.5 Solid-State NMR as a Tool to Study the Quality of Tissue-Engineered Cartilage | 292 | ||
| 10.6 Conclusions | 295 | ||
| References | 296 | ||
| Chapter 11 - Ultrashort Echo Time Imaging of Articular Cartilage | 299 | ||
| 11.1 Introduction | 299 | ||
| 11.2 Morphological UTE Imaging of Articular Cartilage | 301 | ||
| 11.2.1 Multi-Echo UTE Imaging of Articular Cartilage | 301 | ||
| 11.2.2 DIR-UTE Imaging of Articular Cartilage | 302 | ||
| 11.2.3 AWSOS Imaging of Articular Cartilage | 304 | ||
| 11.2.4 SWIFT Imaging of Articular Cartilage | 305 | ||
| 11.3 Quantitative UTE Imaging of Articular Cartilage | 308 | ||
| 11.3.1 T1 Quantification of Calcified Cartilage | 308 | ||
| 11.3.2 T2* Quantification of Calcified Cartilage | 309 | ||
| 11.3.3 T1ρ Quantification of Calcified Cartilage | 310 | ||
| 11.3.4 UTE T2* Bi-Component Analysis of Articular Cartilage | 311 | ||
| 11.3.5 AWSOS T2* Multi-Component Analysis of Articular Cartilage | 315 | ||
| 11.4 Conclusions | 317 | ||
| References | 317 | ||
| Chapter 12 - Low-Field and Field-Cycling NMR and MRI of Cartilage | 320 | ||
| 12.1 Introduction: Low Field vs. Variable Field | 320 | ||
| 12.2 Theoretical Background | 321 | ||
| 12.3 Hardware Considerations | 326 | ||
| 12.3.1 Low-Field Studies: The Single-Sided Scanner | 326 | ||
| 12.3.2 Variable Magnetic Field Strengths by Field Variation | 329 | ||
| 12.3.3 Field-Cycling MRI | 330 | ||
| 12.4 Low-Field Investigations of Cartilage | 331 | ||
| 12.4.1 Relaxation Profiles | 331 | ||
| 12.4.2 Diffusion Profiles | 333 | ||
| 12.4.3 Influence of Sample Curvature and Resolution Limit | 334 | ||
| 12.4.4 Contrast Agents and Enzymes | 334 | ||
| 12.4.5 Cartilage Under Loading | 336 | ||
| 12.5 Variable-Field Studies of Cartilage | 337 | ||
| 12.5.1 Relaxometry Studies | 337 | ||
| 12.5.2 Field-Cycling Imaging | 341 | ||
| 12.6 Summary and Outlook | 343 | ||
| References | 344 | ||
| Chapter 13 - The Influence of Specimen and Experimental Conditions on NMR and MRI of Cartilage | 347 | ||
| 13.1 Introduction | 347 | ||
| 13.2 Pre-Experiment Specimen Preparation and Storage | 348 | ||
| 13.2.1 Specimen Harvesting | 348 | ||
| 13.2.2 Specimen Storage | 350 | ||
| 13.2.3 Alternative Specimens for Articular Cartilage | 352 | ||
| 13.3 Specimen Solutions During NMR and MRI Experiments | 356 | ||
| 13.3.1 NMR/MRI of Cartilage in H2O, Simple Salt and Phosphate-Buffered Solutions | 356 | ||
| 13.3.2 NMR/MRI of Cartilage in Phosphate Salt Solutions | 357 | ||
| 13.3.3 NMR/MRI of Cartilage in Commercial Buffers at Different pH Values | 359 | ||
| 13.3.4 NMR/MRI of Cartilage in Fixation Solutions | 361 | ||
| 13.4 Experimental Issues in NMR and MRI Measurement of Cartilage | 361 | ||
| 13.4.1 Basic Optimization in Experimental Setup and Data Analysis | 362 | ||
| 13.4.2 Effect of the Repetition Time on Cartilage Laminae in MRI | 362 | ||
| 13.4.3 Effect of the Echo Time in Cartilage MRI | 363 | ||
| 13.4.4 Strength of the Spin-Lock Field in Cartilage T1ρ Experiments | 364 | ||
| 13.4.5 Pulse Sequences in Quantitative MRI | 364 | ||
| 13.4.6 Considerations in Multi-Component Relaxation Measurements | 366 | ||
| 13.5 Final Remarks | 367 | ||
| Acknowledgements | 367 | ||
| References | 367 | ||
| Part Three - Biomechanical Properties of Cartilageby NMR and MRI | 373 | ||
| Chapter 14 - Diffusion MRI and Poroelastic Biomechanics of Articular Cartilage | 375 | ||
| 14.1 Introduction | 375 | ||
| 14.2 Cartilage as a Poroelastic Material | 377 | ||
| 14.3 Mechanisms of Cartilage Lubrication | 379 | ||
| 14.4 Microscopic Structure of the Collagen Network | 380 | ||
| 14.5 MRI Methods for Mapping Fluid Translational Motion | 383 | ||
| 14.6 MRI Studies of Cartilage Poroelastic Biomechanics | 386 | ||
| 14.7 Conclusions and Outlook | 390 | ||
| References | 390 | ||
| Chapter 15 - Combining Multi-Modal MRI and Biomechanical Modeling to Investigate the Response of Cartilage and Chondrocytes to Mechanical Stimuli | 395 | ||
| 15.1 Introduction | 395 | ||
| 15.2 Cartilage Architecture and MRI | 397 | ||
| 15.2.1 Cartilage Composition and MRI Morphology | 397 | ||
| 15.2.2 Cartilage Composition and Diffusion | 398 | ||
| 15.2.3 Cartilage Composition and MRI Relaxivity | 399 | ||
| 15.3 Chondrocytes and Mechanical Stimuli | 401 | ||
| 15.3.1 Force Transfer from Global to Cellular Scales | 401 | ||
| 15.3.2 Response of Chondrocytes to Global Stimuli | 402 | ||
| 15.3.3 MRI and Single Chondrocytes | 402 | ||
| 15.4 MRI Measures of Mechanical Behavior | 403 | ||
| 15.4.1 Correlation Between Quantitative MRI and Mechanical Properties | 403 | ||
| 15.4.2 Measurement of Zonal Mechanics by MRI | 403 | ||
| 15.4.3 Measurement of Zonal Mechanics by Magnetic Resonance Elastography | 406 | ||
| 15.4.4 Multi-Modal MRI | 407 | ||
| 15.5 Image-Based Modeling | 409 | ||
| 15.5.1 2D Constitutive Models | 410 | ||
| 15.5.2 3D Constitutive Models | 411 | ||
| 15.5.2.1 Single-Phase Modeling Example | 412 | ||
| 15.5.2.2 Biphasic Modeling Example | 414 | ||
| 15.6 Applications of Image-Based Modeling | 416 | ||
| 15.6.1 Modeling Applications in 2D | 416 | ||
| 15.6.2 Modeling Applications in 3D | 418 | ||
| 15.6.2.1 DTI Experiment | 418 | ||
| 15.6.2.2 Determination of Geometry and Input Data for the Model | 418 | ||
| 15.6.2.3 Single-Phase Modeling Example | 419 | ||
| 15.6.2.4 Bi-Phasic Modeling Example | 420 | ||
| 15.7 Outlook | 421 | ||
| Acknowledgements | 423 | ||
| References | 423 | ||
| Chapter 16 - Loading-Induced Changes in Cartilage Studied by NMR and MRI | 433 | ||
| 16.1 Introduction | 433 | ||
| 16.2 Loading of Articular Cartilage | 434 | ||
| 16.2.1 Mechanical Properties of Articular Cartilage | 434 | ||
| 16.2.2 MRI Study of Cartilage Loading | 436 | ||
| 16.3 Effect of Tissue Loading on T1 Relaxation and GAG Quantification | 437 | ||
| 16.3.1 Strain- and Depth-Dependent Deformation of Articular Cartilage | 437 | ||
| 16.3.2 Critical Point Phenomenon in Compressed Articular Cartilage | 441 | ||
| 16.3.3 Quantification of Gd and GAG Concentrations in Compressed Cartilage | 442 | ||
| 16.4 Effect of Tissue Loading on T2 and T1ρ Relaxation Times | 443 | ||
| 16.4.1 Articular Cartilage Deformation by Proton Images | 443 | ||
| 16.4.2 Articular Cartilage Deformation by T2 and T1ρ Relaxation Times | 444 | ||
| 16.4.3 A Model of Collagen Deformation in Healthy and Lesioned Cartilage | 445 | ||
| 16.5 Functional Study of Human Cartilage using Clinical MRI | 446 | ||
| 16.6 Final Remarks | 448 | ||
| Acknowledgements | 449 | ||
| References | 449 | ||
| Part Four - Applications and the Future of Cartilage Research by NMR and MRI | 455 | ||
| Chapter 17 - The Critical Role of High Imaging Resolution in MRI of Cartilage—The MRI Microscope | 457 | ||
| 17.1 Introduction | 457 | ||
| 17.2 High Resolution in MRI | 458 | ||
| 17.3 Complex Interplay of Imaging Resolution in MRI of Cartilage | 459 | ||
| 17.3.1 Depth-Dependent Zonal Structure of Articular Cartilage | 459 | ||
| 17.3.2 Topographical Distribution of Cartilage Properties | 460 | ||
| 17.3.3 Long Degradation Process with Diverse Early Characteristics | 462 | ||
| 17.3.4 Orientation of the Specimen in the Magnet | 463 | ||
| 17.3.5 Orientation of a Pencil-Shaped Imaging Voxel in MRI | 463 | ||
| 17.3.6 Boundary Tissue Averaging in MRI | 464 | ||
| 17.4 Resolution Scaling Law in MRI of Cartilage | 465 | ||
| 17.5 A Sweet Spot—µMRI of Animal Models of Osteoarthritis | 467 | ||
| 17.6 Final Remarks | 467 | ||
| Acknowledgement | 468 | ||
| References | 468 | ||
| Chapter 18 - Multicomponent Relaxation in NMR and MRI of Cartilage | 471 | ||
| 18.1 Introduction | 471 | ||
| 18.2 Methodological Considerations in Relaxometry | 473 | ||
| 18.2.1 Tissue Heterogeneity and Dipolar Interaction | 473 | ||
| 18.2.2 Ex vivo Sample Handling | 475 | ||
| 18.2.3 NMR and MRI Acquisition Parameters | 476 | ||
| 18.2.4 Multicomponent Analysis | 477 | ||
| 18.2.5 Additional Considerations in Clinical MRI | 479 | ||
| 18.3 Multicomponent NMR Relaxation Studies | 479 | ||
| 18.3.1 Model Systems | 479 | ||
| 18.3.2 Tissue-Engineered Cartilage | 481 | ||
| 18.3.3 Bovine Nasal Cartilage | 483 | ||
| 18.3.4 Articular Cartilage | 485 | ||
| 18.4 Multicomponent MRI Relaxation Studies | 487 | ||
| 18.4.1 Spin Echo Imaging | 487 | ||
| 18.4.2 Gradient Echo Imaging | 488 | ||
| 18.5 Conclusions | 491 | ||
| Acknowledgement | 491 | ||
| References | 491 | ||
| Chapter 19 - Uni- and Multi-Parametric Magnetic Resonance Analysis of Cartilage | 494 | ||
| 19.1 Introduction to Cartilage MRI Classification | 494 | ||
| 19.2 Classification | 497 | ||
| 19.2.1 Sensitivity and Specificity | 497 | ||
| 19.3 Empirical Studies of Univariate Classification of Cartilage | 497 | ||
| 19.3.1 Assignment Based on Euclidean Distance | 498 | ||
| 19.3.2 Assignment Based on Mahalanobis Distance | 499 | ||
| 19.3.3 Limitations to Univariate Classification | 508 | ||
| 19.4 Empirical Studies of Multivariate Classification of Cartilage | 508 | ||
| 19.4.1 Multivariate Classification of Cartilage Using Cluster Analysis | 508 | ||
| 19.4.2 Multivariate Classification of Cartilage Using Support Vector Machine Analysis | 514 | ||
| 19.4.3 Multiexponential and Multivariate Analysis | 516 | ||
| 19.4.4 Application of Machine Learning to Sodium MRI Data | 522 | ||
| 19.4.5 Pattern Recognition and Machine Learning Classification | 524 | ||
| 19.5 Conclusion | 525 | ||
| References | 526 | ||
| Chapter 20 - Magnetic Resonance in the Assessment of Tissue Engineered Cartilage | 529 | ||
| 20.1 Introduction | 529 | ||
| 20.2 Cartilage | 530 | ||
| 20.3 Cartilage Tissue Engineering | 531 | ||
| 20.3.1 Cells | 531 | ||
| 20.3.1.1 Chondrocytes | 531 | ||
| 20.3.1.2 Stem Cells | 532 | ||
| 20.3.2 Scaffolds | 532 | ||
| 20.3.3 Growth Factors and Growth Strategies | 532 | ||
| 20.3.4 Tissue Growth Assessment | 533 | ||
| 20.4 MRS and MRI in Cartilage Tissue Engineering | 533 | ||
| 20.5 Magnetic Resonance Accessible Components of Tissue Engineered and Regenerating Cartilage | 535 | ||
| 20.5.1 Assessment of Tissue Growth | 535 | ||
| 20.5.1.1 Water Proton MRI | 535 | ||
| 20.5.2 Assessment of Tissue Anisotropy and Dynamics | 539 | ||
| 20.5.2.1 Proton NMR Spectroscopy | 540 | ||
| 20.5.2.2 Sodium TQ NMR | 541 | ||
| 20.5.2.3 Diffusion Tensor Imaging | 544 | ||
| 20.5.3 Assessment of GAG Amount | 545 | ||
| 20.5.3.1 Sodium MRI | 545 | ||
| 20.6 Future Directions | 547 | ||
| 20.6.1 New Biomaterials | 547 | ||
| 20.6.2 Magnetic Resonance Standards | 547 | ||
| 20.6.3 ECM-Specific Techniques | 547 | ||
| 20.7 Summary | 548 | ||
| References | 548 | ||
| Chapter 21 - Complementary Imaging in MRI of Cartilage | 552 | ||
| 21.1 Introduction | 552 | ||
| 21.2 Polarized Light Microscopy | 553 | ||
| 21.3 Fourier-Transform Infrared Imaging (FTIRI) | 558 | ||
| 21.4 Electron Microscopy | 561 | ||
| 21.5 Microscopic Computed Tomography | 563 | ||
| 21.6 Additional Imaging Techniques in Cartilage Research | 564 | ||
| 21.7 Final Remarks | 567 | ||
| Acknowledgement | 569 | ||
| References | 569 | ||
| Chapter 22 - Quantitative MRI for Detection of Cartilage Damage | 575 | ||
| 22.1 Introduction | 575 | ||
| 22.2 MRI Biomarkers | 577 | ||
| 22.2.1 Quantitative Morphology | 577 | ||
| 22.2.2 Sodium (Na) Imaging | 577 | ||
| 22.2.3 Delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) | 578 | ||
| 22.2.4 T2 Relaxation Time | 578 | ||
| 22.2.5 Spin-Lattice Relaxation Time in the Rotating Frame (T1ρ) | 578 | ||
| 22.2.6 Magnetization Transfer | 579 | ||
| 22.2.7 Diffusion-Weighted MRI | 579 | ||
| 22.3 Validation of MRI Biomarkers | 580 | ||
| 22.3.1 Techniques Used in the Validation of MRI Biomarkers | 581 | ||
| 22.3.1.1 Cartilage Morphology | 581 | ||
| 22.3.1.2 Methods for Artificial Degradation | 581 | ||
| 22.3.1.3 Histology | 583 | ||
| 22.3.1.4 Cartilage Composition | 585 | ||
| 22.3.2 Clinical MRI | 586 | ||
| 22.3.3 Quantitative Morphology | 590 | ||
| 22.3.4 Biomarkers for Cartilage Composition | 598 | ||
| 22.3.4.1 Differences in MRI Parameters in Healthy and Degraded Cartilage | 598 | ||
| 22.3.4.2 Correlation with Measures of Cartilage Composition and Cartilage Damage | 602 | ||
| 22.3.4.3 Diagnostic Accuracy | 603 | ||
| 22.3.4.4 Limitations of this Comparative Study | 604 | ||
| 22.3.5 Summary | 607 | ||
| 22.4 Validation of Diffusion-Weighted Imaging of Articular Cartilage | 608 | ||
| 22.4.1 Value of DTI for the Detection of Change of Cartilage After Mechanical Injury | 608 | ||
| 22.4.1.1 Study Design | 609 | ||
| 22.4.1.2 MRI Protocol and Image Processing | 609 | ||
| 22.4.1.3 Results and Discussion | 610 | ||
| 22.4.2 Validation of a Clinical Protocol for DTI of Articular Cartilage with Histology | 611 | ||
| 22.4.2.1 MRI Protocol | 613 | ||
| 22.4.2.2 Histology and Image Processing | 614 | ||
| 22.4.2.3 Results and Discussion | 616 | ||
| Acknowledgement | 617 | ||
| References | 617 | ||
| Chapter 23 - Challenges for the Early Detection of Degenerative Cartilage Changes Using Magnetic Resonance Imaging In vivo in Humans | 628 | ||
| 23.1 Introduction | 628 | ||
| 23.2 Morphologic MRI Techniques | 629 | ||
| 23.2.1 Field Strength and Coil | 629 | ||
| 23.2.2 Pulse Sequences | 630 | ||
| 23.2.2.1 2D Spin Echo and Fast Spin-Echo | 631 | ||
| 23.2.2.2 3D Fast Spin-Echo | 632 | ||
| 23.2.2.3 3D Gradient Echo | 632 | ||
| 23.2.2.4 3D Dual-Echo Steady-State | 633 | ||
| 23.2.2.5 Ultrashort Echo-Time | 634 | ||
| 23.3 Quantitative Morphological Measurements of Cartilage | 634 | ||
| 23.3.1 Magnetic Resonance Considerations | 634 | ||
| 23.3.2 Segmentation and Quantification | 635 | ||
| 23.3.3 Semi-Quantitative vs. Quantitative Measurements | 635 | ||
| 23.3.4 Assessment in Osteoarthritis | 637 | ||
| 23.3.5 Assessment After Injury | 639 | ||
| 23.3.6 Assessment After Loading | 639 | ||
| 23.3.7 Measurement Variability | 640 | ||
| 23.4 Quantitative MRI Techniques for Assessment of Cartilage Composition | 640 | ||
| 23.4.1 T2 Relaxation Time Mapping | 641 | ||
| 23.4.1.1 Sequence Considerations | 643 | ||
| 23.4.1.2 Hardware and Software Considerations | 643 | ||
| 23.4.1.3 Segmentation | 644 | ||
| 23.4.1.4 Other Factors | 644 | ||
| 23.4.1.5 Reproducibility and Repeatability | 645 | ||
| 23.4.2 Delayed Gadolinium-Enhanced MRI of Cartilage | 645 | ||
| 23.4.2.1 Sequence Considerations, Reproducibility, and Repeatability | 647 | ||
| 23.4.2.2 Assumptions of GAG Calculation | 648 | ||
| 23.4.2.3 Other Factors | 648 | ||
| 23.4.3 T1ρ Relaxation Time Mapping | 649 | ||
| 23.4.3.1 Sequence Considerations | 650 | ||
| 23.4.3.2 Hardware and Software Considerations | 651 | ||
| 23.4.3.3 Other Factors | 651 | ||
| 23.4.3.4 Reproducibility and Repeatability | 652 | ||
| 23.4.4 Sodium (23Na) Imaging | 652 | ||
| 23.4.4.1 Sequence Considerations | 654 | ||
| 23.4.4.2 Hardware and Software Considerations | 654 | ||
| 23.4.4.3 Other Factors | 654 | ||
| 23.4.4.4 Reproducibility and Repeatability | 654 | ||
| 23.4.5 Diffusion-Weighted Imaging and Diffusion Tensor Imaging | 655 | ||
| 23.4.6 Magnetization Transfer and Chemical Exchange-Dependent Saturation Transfer | 656 | ||
| 23.5 Conclusion | 656 | ||
| References | 657 | ||
| Chapter 24 - Ultrahigh-Field Whole-Body MRI for Cartilage Imaging: Technical Challenges | 671 | ||
| 24.1 Introduction | 671 | ||
| 24.2 Technical Solutions | 674 | ||
| 24.2.1 Overview | 674 | ||
| 24.2.2 Radiofrequency Coil Technology | 675 | ||
| 24.2.3 B1+ Shimming and Parallel Transmission | 681 | ||
| 24.2.4 B1+-Insensitive Radiofrequency Pulse Design | 686 | ||
| 24.2.5 SAR Monitoring and Modeling of Radiofrequency Heating | 686 | ||
| 24.2.6 Field Monitoring and B0 Shimming | 687 | ||
| 24.2.7 Image Acceleration Strategies | 688 | ||
| 24.2.8 Summary | 690 | ||
| 24.3 Emerging Applications | 691 | ||
| 24.3.1 High-Resolution Anatomical Imaging of Cartilage | 691 | ||
| 24.3.2 Quantitative Mapping of Cartilage Damage and Repair | 691 | ||
| 24.3.3 Susceptibility-Weighted Imaging of Cartilage Vascular Canals | 693 | ||
| 24.3.4 UTE Imaging of the Osteochondral Junction | 694 | ||
| 24.3.5 Quantitative Sodium Imaging of Proteoglycan Content | 695 | ||
| 24.4 Outlook | 695 | ||
| References | 697 | ||
| Subject Index | 706 |