Table of Contents
Cover
eMagRes Books
Title Page
Copyright
eMagRes
International Advisory Board
Contributors
Series Preface
Preface
Abbreviations and Acronyms
Part A: Methodology
Basics
Chapter 1: Basics of NMR
1.1 Nuclear Magnetic Resonance
1.2 Relaxation
1.3 Fourier Transform NMR
1.4 NMR Spectroscopy
1.5 Signal-to-Noise Ratio (SNR)
Related Articles in eMagRes
References
Chapter 2: Magnetic Resonance Spectroscopy Instrumentation
2.1 Introduction
2.2 The Magnetic Field
2.3 Radio-Frequency Engineering
2.4 Conclusion
Related Articles in eMagRes
References
Further Reading
Chapter 3: Detection Coils for MRS
3.1 Introduction
3.2 Surface Coils
3.3 Volume Coils
3.4 Transmission Line Coils
3.5 Antennas
References
Chapter 4: A Practical Guide to In Vivo MRS
4.1 Introduction
4.2 The Magnetic Resonance Unit
4.3 The Scanning Procedure
4.4 Post-scan Procedures
Related Articles in eMagRes
References
Localization
Chapter 5: Adiabatic Excitation Pulses for MRS
5.1 Introduction
5.2 Theory
5.3 Applications
Related Articles in eMagRes
References
Chapter 6: Localized MRS Employing Radiofrequency Field (
B
1
) Gradients
6.1 Introduction
6.2 Basics
6.3 The Depth Pulse Method
6.4 Rotating Frame Zeugmatography
6.5 Practical Implementations
6.6 Discussion
6.7 Acknowledgments
References
Chapter 7: Single Voxel MRS
7.1 Introduction
7.2 Single-Voxel Localization Methods
7.3 Practical Considerations
Related Articles in eMagRes
References
Further Reading
Chapter 8: Chemical Shift Imaging with Phase and Sensitivity Encoding
8.1 Introduction
8.2 Basic CSI
8.3 Acquisition-Weighted CSI
8.4
B
0
Correction Methods
8.5 Water and Lipid Suppression Methods
8.6 CSI with Phased Arrays
8.7 Parallel Imaging in CSI
8.8 Clinical Example of CSI
Related Articles in eMagRes
References
Chapter 9: Encoding and Decoding with Prior Knowledge: From SLIM to SPICE
9.1 Introduction
9.2 SLIM: Spectral Localization with Boundary Constraints
9.3 SPICE: High-resolution MRSI with Subspace Constraints
Acknowledgments
References
Chapter 10: Accurate Localized Spectroscopy from Anatomically Matched Regions with Optimal Spatial Response Function
10.1 Introduction
10.2 The Spatial Frontier of In Vivo MR Spectroscopy
10.3 Localization of Anatomically Matched Regions
10.4 Spatial Response Function: The Optimal Experiment
10.5 Biological Applications in Kidney, Eye, and Heart
10.6 Beyond
K
-Space: Nonlinear Gradients
10.7 Discussion and Conclusions
Acknowledgments
References
Further Reading
Chapter 11: Accelerated Spatially-Encoded MRS of Arbitrarily-Shaped Compartments Using Linear Algebraic Modeling
11.1 Introduction
11.2 Localized Spectroscopy with SLAM
11.3 SLAM and Sensitivity Encoding in Higher Dimensions
11.4 Summary of SENSE SLAM Implementation
11.5 An Exemplary Application: Brain
1
H MRS
11.6 Discussion
Acknowledgments
Related Articles in eMagRes
References
Chapter 12: High-Speed Spatial–Spectral Encoding with Echo-Planar and Spiral Spectroscopic Imaging
12.1 Introduction
12.2 Spatial–Spectral Encoding and Reconstruction
12.3 Advanced Topics
12.4 Selected Applications
12.5 Conclusions
Acknowledgments
References
Chapter 13: Direct Water–Fat Imaging Methods: Chemical Shift-Selective and Chemical Shift-Encoded MRI
13.1 Introduction
13.2 Chemical Shift-Selective Imaging
13.3 Chemical Shift-Encoded Water–Fat Imaging
13.4 Conclusion
Acknowledgments
Related Articles in eMagRes
References
Further Reading
Chapter 14: Physiological Maintenance in Animal Experiments
14.1 Introduction
14.2 Pre-scanning Animal Maintenance
14.3 Anesthesia and Immobilization
14.4 Temperature Monitoring and Control
14.5 Animal Jigs and Coils
14.6 Post-scanning Maintenance
Acknowledgments
References
Physiological Monitoring
Chapter 15: Physiological Maintenance in MRI and MRS of Large Animals
15.1 Introduction
15.2 Equipment
15.3 The MRS/MRI Animal Environment
15.4 Anesthesia
15.5 Inherent Risk Factors
15.6 Conclusion
References
Further Reading
Chapter 16: Physiological Monitoring in Human MRS
16.1 Introduction
16.2 General Safety Considerations of Monitoring in the MR Environment
16.3 Selection of Parameters to Monitor
16.4 Other Considerations for Subject Comfort
16.5 Commonly Used Monitoring Equipment
16.6 Special Circumstances
16.7 Conclusions
References
Chapter 17: Physiologic Motion: Dealing with Cardiac, Respiratory, and Other Sporadic Motion in MRS
17.1 Introduction
17.2 Types of Physiologic Motion
17.3 Impact of Motion on MRS
17.4 Techniques to Compensate for Physiologic Motion in MRS
Related Articles in eMagRes
References
Data Analysis
Chapter 18: Quantifying Spectra in the Frequency Domain
18.1 Introduction
18.2 Frequency-domain Analysis Methods
18.3 Data Acquisition Considerations
18.4 Summary
Acknowledgments
List of Abbreviations
References
Chapter 19: Quantifying Spectra in the Time Domain
19.1 Introduction
19.2 Parametric vs Semiparametric Estimation
19.3 Estimating Errors Using the Cramér–Rao Bounds
19.4 Prior Knowledge and Metabolite Quantification Algorithms
19.5 Practical Examples of Processing Using jMRUI
19.6 Conclusions
Acknowledgments
References
Chapter 20: Advanced Spectral Quantification: Parameter Handling, Nonparametric Pattern Modeling, and Multidimensional Fitting
20.1 Introduction
20.2 Modeling: Line Shapes, Baselines, and Unknown Peaks
20.3 Optimization Algorithms
20.4 Multidimensional Spectral Fitting
20.5 Accuracy and Precision of Spectral Fitting Methods
Acknowledgments
List of Abbreviations
References
Chapter 21:
1
H-NMR Chemical Shifts and Coupling Constants for Brain Metabolites
21.1 Introduction
21.2 Experimental Conditions
21.3 Spectral Parameters of Brain Metabolites
21.4 Conclusions
21.5 Acknowledgments
References
Chapter 22: Pattern Recognition Analysis of MR Spectra
22.1 Introduction
22.2 Data
22.3 Lessons Learned from Previous Studies
22.4 Acknowledgments
References
Chapter 23: Quantifying Metabolite Ratios and Concentrations by
1
H MRS
23.1 Introduction
23.2 Peak Identification
23.3 Peak Referencing
23.4 Relaxation Correction
23.5 Tissue Analysis
23.6 CSI Quantification
23.7 Chemical Shift Displacement (CSD)
23.8 Interpretation
Related Articles in eMagRes
References
Chapter 24: Quantifying Metabolite Ratios and Concentrations by Non-
1
H MRS
24.1 Introduction
24.2 NMR Signal, Nuclear Density, and Concentration
24.3 Metabolite Ratios
24.4 Absolute Metabolite Concentrations
24.5 Examples
24.6 Conclusion
Related Articles in eMagRes
References
Parametry
Chapter 25: Measuring Intra- and Extracellular pH by MRS
25.1 Introduction
25.2 A Brief Survey of Non-MRS-Based pH Measurements
25.3 MRS-Based pH Measurements
25.4 Conclusions and Predictions
Related Articles in eMagRes
References
Chapter 26: Temperature Monitoring Using Chemical Shift
26.1 Introduction
26.2 Principles
26.3 Comparison of the Acquisition Techniques
26.4 Absolute Temperature Measurement
26.5 Concluding Remarks
Acknowledgments
References
Chapter 27: Diffusion-Weighted MRS
27.1 Introduction
27.2 Diffusion of Metabolites: Specific Probes of the Intracellular Space
27.3 Methods for Measuring Metabolite Diffusion
27.4 Applications of DW-MRS: Insights, Diseases, Microstructures, and Physiology
27.5 Conclusion
Related Articles in eMagRes
References
Chapter 28: Measuring Biochemical Reaction Rates In Vivo with Magnetization Transfer
28.1 Introduction
28.2 Theory
28.3 Acquisition Methods
28.4 Conclusions
Related Articles in eMagRes
References
Chapter 29: Proton Chemical Exchange Saturation Transfer MRS and MRI
29.1 Introduction
29.2 MRS of Exchangeable Protons
29.3 Chemical Exchange Saturation Transfer (CEST)
29.4 Pulse Sequences for MTC and CEST MRI
29.5 Data Analysis for CEST Spectra
29.6 Potential and Clinical Translation of CEST Methods
29.7 Conclusions
Acknowledgments
List of Abbreviations
References
Chapter 30: Two-Dimensional NMR Spectroscopy Plus Spatial Encoding
30.1 Introduction
30.2 Single-voxel-based 2D MRS
30.3 Echo-planar Correlated and
J
-resolved MRSI
30.4 Accelerated Echo-planar
J
-resolved MRSI with Nonuniform Undersampling and Compressed Sensing
30.5 Prior-knowledge Fitting for Metabolite Quantitation
30.6 Future Directions: Clinical Applications
Acknowledgments
References
Chapter 31: Spectral Editing
31.1 Introduction
31.2 Theory
31.3 Practical Considerations
31.4 Summary and Conclusions
Related Articles in eMagRes
References
Chapter 32: Multiple Quantum MRS
32.1 Introduction and Theoretical Background
32.2 Deuteron (
2
H;
I
= 1) Interactions
32.3 Sodium (
23
Na;
I
= 3/2) Interactions
32.4 Brain
32.5 Optic and Sciatic Nerves
32.6
23
Na
32.7 Cartilage
32.8
2
H
32.9
23
Na
32.10 Tendon
32.11 Intervertebral Discs (IVDs)
32.12 Red Blood Cells (RBCs)
32.13 Muscles
32.14 Heart
Related Articles in eMagRes
References
Hyperpolarization
Chapter 33: Hyperpolarization Methods for MRS
33.1 Introduction
33.2 Dynamic Nuclear Polarization (DNP)
33.3
para
-Hydrogen (
para
-H
2
) Production
33.4
para
-Hydrogen-Induced Polarization (PHIP)
33.5 Signal Amplification by Reversible Exchange (SABRE)
33.6 Spin-exchange Optical Pumping (SEOP)
33.7 Conclusions
Acknowledgments
References
Chapter 34: Pulse Sequences for Hyperpolarized MRS
34.1 Introduction
34.2 Evolution of Hyperpolarized Agents
34.3 RF Pulse Strategies
34.4 Acquisition Strategies
34.5 Summary
Software Resources
Acknowledgments
References
Part B: Applications
Cells, Solutions
Chapter 35: MRS of Perfused Cells, Tissues, and Organs
35.1 Introduction
35.2 Initial Perfused Cell and Organ Studies
35.3 Isotopic Perfused Cell and Organ Studies
35.4 Cell and Organ Perfusion
35.5 The Perfusion Apparatus
35.6 Summary
Acknowledgments
References
Chapter 36: Metabolism and Metabolomics by MRS
36.1 Introduction
36.2 Ex Vivo MRS Methods for Studying the Metabolome
36.3 MRS of Cellular Processes
36.4 Metabolomic Studies of Diseases
Related Articles in eMagRes
References
Fluorine and Carbon
Chapter 37: In Vivo
19
F MRS
37.1 Introduction
37.2 Properties of the
19
F Nucleus for In Vivo Magnetic Resonance
37.3 Hardware for In Vivo
19
F MR Spectroscopy
37.4
19
F MR Spectroscopy Acquisition Methods
37.5 Quantification and Sensitivity in
19
F MR Spectroscopy
Acknowledgments
References
Chapter 38:
13
C MRS in Human Tissue
38.1 Introduction
38.2 Methods
38.3 Applications: Tissue Lipid Profiling and Assessment
38.4 Skeletal Muscle Metabolism
38.5 Liver Metabolism
38.6 Brain
38.7 Conclusion
References
Chapter 39: Hyperpolarized
13
C MRI and MRS Studies
39.1 Introduction
39.2 Dissolution Dynamic Nuclear Polarization (dDNP)
39.3 Acquisition Techniques for Hyperpolarized
13
C Imaging
39.4 In Vivo Applications of Hyperpolarized
13
C MRI
39.5 Translation to the Clinic
39.6 Summary
Related Articles in eMagRes
References
Chapter 40: Integrating
13
C Isotopomer Methods with Hyperpolarization for a Comprehensive Picture of Metabolism
40.1 Introduction
40.2
13
C NMR Spectroscopy and
13
C Isotopomers
40.3 The Citric Acid Cycle and its Role in Energy Capture and Biosynthesis
40.4 Combining
13
C Isotopomer and Dynamic HP Data to Evaluate Flux in Cancer Cells
40.5 HP and the Heart
40.6 HP and the Liver
40.7 Summary
Acknowledgments
Related Articles in eMagRes
References
Muscle
Chapter 41: Muscle Studies by
1
H MRS
41.1 Introduction
41.2 Consequences of Structural Order and Tissue Compartmentation on H-MR Spectra
41.3 Methodological Aspects of H-MRS
41.4 Diffusion Spectroscopy
41.5 Applications of H-MRS in Studies on Human Metabolism
41.6 Conclusions
Related Articles in eMagRes
References
Chapter 42: Muscle Studies by
31
P MRS
42.1 Introduction
42.2 Some Background
42.3 Resting Muscle
42.4 Exercise Manipulations
42.5 Other Uses of
31
P MRS Data
42.6 Conclusion: What We Do and Do Not Know
Acknowledgments
Abbreviations
Symbols
Subscripts
Values
Related Articles in eMagRes
References
Chapter 43: Measuring Intracellular Oxygenation with Myoglobin
1
H MRS
43.1 Introduction
43.2 Overview of Current Techniques
43.3 Myoglobin
43.4 Paramagnetic Interactions
43.5 The Proximal Histidyl F8 N
δ
H Signal
43.6 The Val-E11
γ
1-CH
3
Signal
43.7 Spectroscopic Considerations for
In Vivo
Applications
43.8 The Proximal Histidyl-N
δ
H Signal from Myocardium
43.9 Potential Interference in Detecting Deoxy-Mb Signal
43.10 The Val-E11
γ
1
-CH Signal from Myocardium
43.11 Assessing Cellular Oxygenation
43.12 Critical PO
2
43.13 Hemoglobin
43.14 Skeletal Muscle Metabolism
43.15 Intracellular VO
2
43.16 Summary
Acknowledgments
Related Articles in eMagRes
References
Further Reading
Obesity and Diabetes
Chapter 44: Body Fat MRS
44.1 Introduction
44.2 Composition of Adipose Tissue
44.3 Whole Body Adiposity
44.4 Ectopic Fat
44.5 Bone Marrow
44.6 Brown Adipose Tissue
Related Articles in eMagRes
References
Chapter 45: In Vivo MRS of Lipids in Adipose Tissue, Bone Marrow, and Liver
45.1 Introduction
45.2 Adipose Tissue
45.3 Bone Marrow
45.4 Liver
45.5 Conclusions
Related Articles in eMagRes
References
Chapter 46: Assessing Fatty Liver with MRS
46.1 Introduction
46.2 MRS Quantification of Liver Fat Content
46.3 Multivoxel MRS
46.4 Fat Composition
46.5 Liver Fat Contents in Fasted and Fed States; Exercise
46.6
1
H MRS in Fatty Liver Disease
46.7
1
H MRS of the Liver in Diabetes
46.8 Other Applications of MRS in the Study of Diffuse Liver Disease
46.9 Future Prospects
Related Articles in eMagRes
References
Chapter 47: MRS Studies of Muscle and Heart in Obesity and Diabetes
47.1 Introduction
47.2 Glucose Disposal and Glycogen Synthesis in Skeletal Muscle
47.3 Lipid Metabolism in Skeletal Muscle
47.4 Energy Metabolism in Skeletal Muscle
47.5 Lipid Metabolism in the Heart
47.6 Energy Metabolism in the Heart
47.7 Ion Homeostasis in the Heart
47.8 Conclusions and Outlook
Acknowledgments
References
Chapter 48: Studying Cardiac Lipids in Obese and Diabetic Patients by
1
H MRS
48.1 Introduction
48.2 Research Linking Intramyocardial Triglyceride to Myocardial Dysfunction
48.3 The ‘Nuts and Bolts’ of Cardiac H MRS In Vivo
48.4 Overview of the Present Status of Cardiac H MRS
48.5 Conclusions and Future Outlook
References
Heart Disease
Chapter 49: Cardiac MRS Studies in Rodents and Other Animals
49.1 Introduction
49.2
31
P MRS and Cardiac Energy Metabolism
49.3
1
H Magnetic Resonance Spectroscopy
49.4 Carbon-13 Magnetic Resonance Spectroscopy
49.5 Cation MRS
49.6 Conclusion
References
Chapter 50: Assessing Cardiac Transplant Viability with MRS
50.1 Introduction
50.2 Biomarkers for Graft Viability before Transplantation
50.3 Viability of the Graft after Transplantation
50.4 Conclusion
Acknowledgments
Related Articles in eMagRes
References
Chapter 51: MRS in the Failing Heart: From Mice to Humans
51.1 Introduction
51.2 CK Energy Reserve in Heart Failure
51.3 The CK ATP Energy Supply Rate in HF
51.4 Insights on the Role of CK from Genetic Modeling
51.5 Clinical Events and Future
Acknowledgments
References
Chapter 52: MRS Studies of Creatine Kinase Metabolism in Human Heart
52.1 Introduction
52.2 Methods
52.3 Results
52.4 Conclusions
Acknowledgments
Related Articles in eMagRes
References
Brain
Chapter 53: Studying Aging, Dementia, Trauma, Infection, and Developmental Disorders of the Brain with
1
H MRS
53.1 Introduction
53.2 Aging and Dementia
53.3 Traumatic Brain Injury
53.4 MRS of CNS Infections
53.5 MRS Studies of Developmental Disorders
Acknowledgments
References
Chapter 54: Studying Stroke and Cerebral Ischemia by
1
H MRS
54.1 Introduction
54.2 The Metabolic Consequences of Reduced Blood Flow – What Are the Targets for MRS Investigation in Ischemia?
54.3 Methodological Considerations for Routine Proton MRS in Cerebral Ischemia
54.4 Measurement of Brain Lactate in Ischemia and Stroke – A Brief Historical Perspective of Clinical Investigations
54.5 Confounding Factors in Measurement of Brain Lactate
54.6 Summary
Acknowledgments
References
Chapter 55:
31
P MRS in Psychiatric Disorders
55.1 Introduction
55.2 Basic Brain
31
P MRS
55.3
31
P MRS Studies of Energetics in Psychiatric Illness
55.4 Membrane Metabolism and
31
P MRS
55.5 Conclusion
References
Chapter 56: The Significance of
N
-Acetyl Aspartate in Human Brain MRS
56.1 Introduction
56.2 MRS Measures Concentration
56.3 Pathways and Roles of NAA
56.4 One Metabolite, Many Roles
56.5 Interpretation of NAA
56.6 Conclusion
56.7 Acknowledgments
Related Articles in eMagRes
References
Cancer
Chapter 57: MRS in Brain Cancer
57.1 Introduction
57.2
1
H MRS Metabolic Profiles of Brain Tumors
57.3
1
H MRS Data Acquisition
57.4 MRS Data Analysis
57.5
1
H MRS Biochemicals and Brain Tumor Biomarkers
57.6
1
H MRS Characteristics of Brain Tumor-like Lesions
57.7
1
H MRS for Treatment Planning and Assessing Response
57.8
31
P and
13
C MRS of Brain Tumors
57.9 Future Directions of Brain Tumor
1
H MRS
Acknowledgments
References
Chapter 58: MRS in Breast Cancer
58.1 Introduction – Breast Cancer Physiology and MRS
58.2 Technique of In Vivo MR Spectroscopy (MRS)
58.3 Applications of
1
H MRS in the Clinical Setting
58.4 Summary, Limitations, and Future Directions
Acknowledgments
Related Articles in eMagRes
References
Chapter 59: MRS in Prostate Cancer
59.1 Introduction
59.2 Unique Metabolism of Prostate Cancer Probed by Preclinical MRS
59.3 Clinical Applications of Prostate Spectroscopy
Related Articles in eMagRes
References
Clinical Trials
Chapter 60: Clinical Trials of MRS Methods
60.1 Introduction
60.2 Methods Used in Clinical Trials of MRS
60.3 Achievements of MRS Trials
References
Chapter 61: Clinical Trials that Utilize MRS as a Biomarker
61.1 Introduction
References
Part C: Appendices
Appendix 1 : Properties of NMR-Visible Isotopes and their Biological Content in Human Tissues
Related Articles in eMagRes
References
Appendix 2 : Concentration Ranges of Common Metabolites Detected by MRS in Healthy Human Tissue
References
Appendix 3 : Peak Assignments for Some Common Metabolites
References
Appendix 4 : Biochemical Reactions and Molecular Structures of Common MRS Metabolites
Appendix 5 : Some Standard Formulae Used in MRS
5.1 Basic NMR Equations
5.2 Signal-to-Noise Ratio
5.3 Signal Processing
5.4 Physiological
References
Appendix 6 : Common MRS Artifacts
References
Appendix 7 : In Vivo Spectra with Peak Assignments
References
Index
End User License Agreement
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781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
809
810
811
812
813
814
815
816
817
818
819
821
823
824
825
826
827
828
829
830
831
832
833
834
835
837
838
839
840
841
842
843
844
845
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
893
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
947
948
949
950
951
952
953
954
955
957
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1025
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1051
1053
679
680
681
682
683
684
685
686
687
688
689
690
691
692
779
1054
1055
1056
1057
1058
1059
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1075
1076
1077
1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
1103
1104
1105
1106
1107
1108
1109
1110
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
1149
1150
1151
1152
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162
1163
1164
1165
1166
1167
1168
1169
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
1189
1190
1191
1192
1193
Guide
Cover
Table of Contents
Preface
Begin Reading