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Increased PK11195 PET binding in the cortex of patients with MS correlates with disability

Objective: Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability. Methods: Using PET and optimized modeling and segmentation procedures, we investigated cortical 11C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29). Results: Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS. Conclusions: Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM.