P. Michael Conn9780121827908, 0121827909
Table of contents :
00 385mie.jpg……Page 1
01 fm.pdf……Page 2
02 preface.pdf……Page 3
04 contributors.pdf……Page 4
Introduction……Page 7
Drug Evaluation……Page 8
Biological Function Evaluation……Page 9
PET in Oncology……Page 10
Differential Diagnosis: Benign versus Malignant Lesions……Page 11
Diagnosis and Initial Staging……Page 12
Response to Treatment……Page 14
Recurrence/Restaging……Page 15
Epilepsy……Page 16
Movement Disorders……Page 17
Cardiac Neurotransmission……Page 18
Prosthetic Joint Infections……Page 19
Assessment of Multidrug Resistance……Page 20
Tumor Hypoxia……Page 21
Gene Expression……Page 22
Conclusions……Page 23
Introduction……Page 24
Spin Relaxation……Page 25
Effects of Exchange and Compartmentation……Page 29
Paramagnetic Relaxation……Page 30
Susceptibility Contrast and BOLD Effects……Page 31
Effects of Spin Motion……Page 32
An Illustrative Example: MRI of Exercising Skeletal Muscle……Page 33
Transverse Relaxation Studies of Water Compartmentation……Page 34
Physiological Influences on NMR Relaxation in the Intracellular Space……Page 37
Physiological Influences on NMR Relaxation in the Interstitial Space……Page 41
Physiological Influences on NMR Relaxation in the Vascular Space……Page 42
Conclusion: How Can We Use Transverse Relaxation Measurements to Learn about Exercising Muscle?……Page 44
Introduction……Page 46
Nuclear Magnetic Resonance Basics……Page 47
In Vivo NMR Imaging and Spectroscopy of Animals……Page 49
Practicalities and Optimized Radio Frequency Hardware for In Vivo NMR Spectroscopy of the Mouse……Page 53
Standard Setup……Page 54
General Coil Design……Page 55
31P NMR Spectroscopy of Mouse Hind Limb……Page 57
1H NMR of Mouse Skeletal Muscle……Page 59
31P NMR Spectroscopy of Mouse Brain……Page 61
Mouse Brain Proton NMR……Page 62
Anesthesia and Physiological Monitoring of Animals in NMR Experiments……Page 63
NMR and Animal Use……Page 67
Acknowledgments……Page 68
Introduction……Page 69
Fabrication of Stereotaxic Apparatus……Page 72
Selection of Suitable Materials for Implantation……Page 74
Implantation of Electrodes……Page 75
Training of Animals……Page 78
Sleep Deprivation……Page 79
MRI Experiments……Page 80
Artifacts in MR Images……Page 82
Susceptibility and Other Artifacts……Page 83
Other Precautionary Measures Adopted……Page 86
Safety Aspects……Page 88
Conclusions……Page 89
Acknowledgments……Page 90
Introduction……Page 91
Potential of Functional MRI in Macaque Monkeys……Page 92
Brief History of fMRI in Macaque Monkeys……Page 93
fMRI in Awake Monkeys……Page 95
Scan Procedures……Page 96
Conclusion……Page 97
Need for Three-Dimensional Atlas Template Image for Nonhuman Studies……Page 98
Image Acquisition……Page 99
Template Image Development……Page 100
Validation……Page 103
Macaque Template Images: The “n2k” and “n2kf” Templates……Page 104
Registering a PET Image to Atlas Space……Page 105
Use in SPM Analysis……Page 106
Future Applications……Page 107
Abstract……Page 108
Acknowledgments……Page 109
The Need for Primate Functional Magnetic Resonance Imaging (fMRI)……Page 110
Conventional BOLD……Page 115
Cerebral Blood Flow……Page 117
Cerebral Blood Volume……Page 119
Optimizing Pulse Sequences for Monkeys……Page 124
Spatial Resolution……Page 125
Horizontal vs Vertical Orientation……Page 126
Anesthetized vs Awake……Page 127
Restraint……Page 129
Training……Page 130
Hygiene……Page 131
MRI Hardware……Page 132
Experimental Design……Page 133
Postprocessing……Page 135
A Common Platform for Comparing Monkey and Human Neuroimaging……Page 137
Retinotopic Mapping in Monkey and Human Visual Cortex……Page 138
Conclusions……Page 141
Acknowledgments……Page 142
Introduction……Page 143
Blood Oxygenation and MRI……Page 144
Rapid MRI for fMRI……Page 147
Experimental Design……Page 149
Analysis of Images……Page 152
Model-Based Detection of the BOLD Signal……Page 153
Statistical Inference and Thresholding of Activations……Page 154
An Application of Functional MRI……Page 156
Discussion and Conclusion……Page 157
Introduction……Page 158
Vacuum Pumps and Gas Admission Module……Page 161
Optical Pumping Module……Page 162
Laser-Polarized 129Xe NMR Specificities……Page 163
Delivering HP129Xe to the Brain……Page 165
Rationale of the Method……Page 166
Animal Preparation Procedures……Page 170
HP Tracer Injection……Page 171
Results……Page 172
Acknowledgments……Page 174
Introduction……Page 175
Basic Principles……Page 176
Distinctions Between In Vivo and In Vitro Methods……Page 177
Potential Confounds in In Vivo Methods……Page 178
Pharmacological Interventions……Page 179
Nonsequential Studies……Page 180
Specific Activity Adjustment……Page 181
General Experimental Procedure……Page 182
Data Reduction……Page 183
Parameter Optimization……Page 184
Distinction of Density from Affinity Effects……Page 186
Sequential vs Nonsequential Studies……Page 188
Conclusions……Page 189
Acknowledgments……Page 190
Introduction……Page 191
Compartmental Models……Page 194
Standard Model Equations……Page 196
M-I Model Equations……Page 198
Animal Preparation……Page 201
Measuring Blood Activity and Constructing Input Curves……Page 203
Generation of Regional Time-Activity Curves (TACs) from PET Images……Page 204
Implementing Model Equations……Page 206
Parameter Estimation……Page 207
Numerical Solution of Differential Equations……Page 209
Validating Parameter Estimates……Page 211
Results and Interpretation……Page 212
Examination of Residuals……Page 213
Parameter Precision……Page 214
Model Selection/Goodness of Fit……Page 215
Sensitivity Functions……Page 216
Using the Sensitivity Information for Design……Page 218
Design Variables……Page 219
Conclusion……Page 220
Introduction……Page 221
Animal Preparation……Page 223
[11C]Raclopride Preparation and Administration……Page 224
MicroPET R4 Configuration……Page 225
Scatter Correction……Page 226
Attenuation Correction……Page 228
Image Reconstruction……Page 229
Graphical Analysis of Region of Interest Data……Page 231
Summary of Results……Page 234
Acknowledgments……Page 236
Introduction……Page 237
Instrumentation……Page 240
Radioligand Application……Page 241
Evaluation……Page 242
Results and Discussion……Page 244
Acknowledgments……Page 248
Introduction……Page 249
Drug Imaging and Pharmacokinetic Studies……Page 250
Noninvasive Assessment of Drug Efficacy/Pharmacodynamic Studies……Page 252
Qualitative Characterization……Page 253
Physiological Parameters……Page 254
Tissue Oxygenation……Page 256
Vascular Permeability……Page 258
Disease and Efficacy Biomarkers as Bridge between Preclinical and Clinical Drug Evaluation……Page 261
Conclusion and Outlook……Page 264
Use of NADH Fluorescence in Biochemistry and Biology……Page 266
Photophysics of NADH……Page 268
Cellular NADH Fluorescence……Page 269
Optical System for Microcuvette ED-FRAP Experiments……Page 272
Kinetic Model Description of NADH ED-FRAP……Page 274
NADH ED-FRAP Measurement of Kinetic Parameters in Isolated Mitochondria……Page 278
Confocal NADH ED-FRAP Imaging……Page 282
Potential for Multiphoton and Wide-Field NADH ED-FRAP Imaging……Page 290
Summary……Page 294
Acknowledgments……Page 295
Introduction……Page 296
Overview of the Production of Carbon-11……Page 298
Synthesis Modules……Page 301
1-[11C]D-Glucose……Page 302
[1-11C]Palmitate……Page 305
1-[11C] Acetate……Page 306
Overview of the Quality Assurance of C-11 Radiopharmaceuticals……Page 308
Radionuclidic Purity……Page 309
Radioactivity Balance……Page 310
Sterility, Apyrogenicity, Isotonicity, and Acidity……Page 311
Dosimetry Calculations……Page 312
Data Reconstruction and Generation of Time-Activity Curves……Page 313
Determination of [11 C]CO2……Page 315
Kinetic Modeling……Page 316
Myocardial Blood Flow (MBF)……Page 317
Myocardial Glucose Utilization……Page 319
Myocardial Fatty Acid Metabolism……Page 322
Conclusion……Page 324
Acknowledgments……Page 325
Introduction……Page 326
Some Issues Specific to Pulmonary PET……Page 327
General Approaches to Evaluating Enzyme Function with PET……Page 328
Pulmonary Angiotensin-Converting Enzyme (ACE) Expression……Page 329
Inflammation Imaging of Lungs……Page 331
Quantitation Issues……Page 334
Validation Issues……Page 336
Gene Expression Imaging……Page 338
PET Imaging Protocol……Page 342
Image Analysis……Page 343
Acknowledgments……Page 344
Introduction……Page 345
No-Carrier-Added Synthesis of [11C]Toluene……Page 346
Radiochromatography System for Tracer Purification Using Supercritical CO2 Fluid as the Mobile Phase……Page 347
PET Studies of [11C]Toluene in Baboons……Page 348
Assay of [11C]Toluene and Its Metabolites in Baboon Plasma……Page 349
Image ROI Analysis……Page 351
Baboon Studies……Page 353
Mouse Dissection Experiments……Page 355
Discussion……Page 357
Acknowledgments……Page 360
Introduction……Page 361
Two-Hybrid Systems……Page 362
Protein-Fragment Complementation……Page 363
Other Strategies……Page 364
Detecting Protein-Protein Interactions in Living Animals……Page 365
Optimizing Luciferase Fragments for Complementation……Page 366
Mammalian Expression Constructs……Page 367
Determining the Fidelity of Optimized LCI for Reporting Protein Association……Page 368
Technical Considerations for LCI in Mouse Models……Page 369
Selection of Applications and Model Systems for LCI……Page 371
Acknowledgments……Page 372
The NADH Compound of Mitochondria……Page 373
Functional Activation……Page 375
Bleaching of Fluorescence……Page 377
In Vivo Location of the Fluorescent Signal……Page 378
High-Resolution Cryoimaging……Page 379
The Future-High Resolution Metabolic Histopathology……Page 382
x subject index.pdf……Page 383
xx author index.pdf……Page 392
xxx mie index.pdf……Page 416
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