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Table of contents
LIST OF FIGURES
LIST OF TABLES
ABBREVIATIONS
INTRODUCTION
MULTIPLE SCLEROSIS: FROM INFLAMMATION TO NEURODEGENERATION
1. GENERAL CONSIDERATIONS
1.1. EPIDEMIOLOGY
1.2. DIAGNOSIS OF MULTIPLE SCLEROSIS
1.3. EVOLUTION AND PROGNOSIS
2. MECHANISMS OF DISABILITY PROGRESSION
2.1. WHITE MATTER DAMAGE
2.2. GREY MATTER INVOLVEMENT
IMAGING NEURODEGENERATION IN THE MS GREY MATTER
1. GREY MATTER ATROPHY
2. QUANTITATIVE MRI
2.1. DIFFUSION TENSOR IMAGING
2.2. MAGNETIZATION TRANSFER IMAGING (MTI)
2.3. PROTON MAGNETIC RESONANCE SPECTROSCOPY
3. POSITRON EMISSION TOMOGRAPHY
3.1. PRINCIPLES OF PET IMAGING
3.2. [18F]-FLUORODEOXYGLUCOSE (FDG) PET AND NEURONAL METABOLISM
3.3. FLUMAZENIL, AN ANTAGONIST OF THE CENTRAL BENZODIAZEPINE RECEPTOR
IMAGING NEURONAL DAMAGE IN THE MS GREY MATTER USING PET WITH [11C]FMZ
1. SPECIFIC AIMS OF THE STUDY
2. MATERIAL AND METHODS
2.1. SUBJECTS
2.2. CLINICAL EVALUATION
2.3. MAGNETIC RESONANCE IMAGING DATA ACQUISITION
2.4. PET ACQUISITION AND QUANTIFICATION
2.5. PROCESSING
2.6. STATISTICAL ANALYSES
3. RESULTS
3.1. CHARACTERISTICS OF MS PATIENTS AND HEALTHY CONTROLS
3.2. [11C]FMZ BINDING IN THE GREY MATTER
3.3. GM ATROPHY IN MS PATIENTS
3.4. REDUCED [11C]FMZ BINDING IN THE MS GM
3.5. SUBGROUP ANALYSES OF [11C]FMZ BINDING
3.6. CORTICAL MAPPING OF [11C]FMZ BINDING CHANGES
3.7. RELATIONSHIP BETWEEN [11C]FMZ BINDING AND WHITE MATTER LESIONS LOAD
3.8. RELATIONSHIP BETWEEN [11C]FMZ BINDING AND CLINICAL METRICS
DISCUSSION & PERSPECTIVES
1. IN VIVO QUANTIFICATION OF NEURONAL DAMAGE IN MS
2. CLINICAL RELEVANCE OF PET WITH [11C]FMZ
3. UNDERLYING MECHANISMS OF NEURONAL DAMAGE IN MS
3.1. RELATIONSHIP BETWEEN WM AND GM DAMAGE
3.2. RELATIONSHIP BETWEEN GM DEMYELINATION AND NEURODEGENERATION
3.3. OTHER ASPECTS
4. FUTURE ROLE OF [11C]FMZ PET IN MS
5. LIMITS OF PRESENT STUDY
CONCLUSION
ANNEX
1. ANNEX A
2. ANNEX B
3. ANNEX C
