In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

: 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 [-(11)C-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 (11)C-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 (11)C-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 (11)C-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.