In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI
Technical Report,01 Sep 2015,31 Aug 2016
Massachusetts General Hospital Boston United States
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Post-mortem studies in multiple sclerosis MS suggested that cortical demyelinating lesions, which are hardly detected in vivoon conventional magnetic resonance imaging MRI scans, are an important correlate of disability, and are driven by organized neuroinflammation with the activation of microglia. Activated microglia up-regulate expression of the 18kDa translocator protein TSPO, which can be imaged in vivo with -11C-PBR28, a second generation TSPO ligand. In this study, we combined ultra-high field 7 Tesla T MRI, which has demonstrated greater sensitivity to cortical lesions than conventional MRI, with 11C-PBR28 positron emission tomography PET imaging of activated microglia to assess whether more severe structural cortical pathology in MS is related to the presence of neuroinflammation. We found that, relative to healthy controls, MS subjects exhibited abnormally high 11C-PBR28 binding across the brain, the greatest increases being incortex and cortical lesions, deep gray matter GM but also and in normal appearing white matter NAWM. The observed increased 11C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance in the cortex it correlated with cortical demyelination as measured by 7T MRI. Quantification of TSPO levels in MS could prove a sensitive tool for evaluating in vivo neuroinflammation and its correlates.
- Medicine and Medical Research