The overarching aim is to assess the role of microglial activation and norepinephrine transporter binding in pathogenesis of MS-related fatigue, using novel Positron Emission Tomography (PET) radiotracers, [F-18]PBR06 and [C-11]MRB. Specific Aims: Specific Aim 1: To determine the relationship of cerebral microglial activation, as assessed by [F-18]PBR06 PET, with MS-related fatigue. Specific Aim 2: To determine the relationship of norepinephrine transporter (NET) binding, as assessed by [C-11]MRB PET, with MS-related fatigue. Specific Aim 3: To determine the relationship of microglial activation and NET binding, with grey matter pathology (lesion load and brain atrophy) assessed using 7T MRI, and evaluate their independent contribution in development of MS-related fatigue.
Name: [F-18]PBR06
Name: [C-11]Methylreboxetine
Description: PET outcome measure
Measure: Standardized Uptake Value (SUV)/Standardized Uptake Value Ratio (SUVR) Time: BaselineDescription: Clinical outcome measure; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes.
Measure: Modified Fatigue Impact Scale (MFIS) Time: BaselineDescription: PET outcome measure
Measure: Binding Potential (BPnd) Time: BaselineDescription: MRI outcome measure
Measure: MRI grey matter lesional load/brain atrophy Time: BaselineDescription: PET outcome measure
Measure: Tissue Volume of distribution (Vt)/Distribution Volume Ratios (DVR) Time: BaselineDescription: MRI outcome measure
Measure: MRI global/regional volumetrics Time: BaselineAllocation: N/A
Single Group Assignment
There is one SNP
Clinical Data The following non-imaging, clinical data will be obtained: Modified fatigue Impact Scale (MFIS) Fatigue Severity Status Scale (FSSS) Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS) --- T25W ---