DGM atrophy is a proposed biomarker for neurodegeneration in MS but its pathogenesis is not clear. [F-18]PBR06 is a novel, long half-life PET tracer for assessing microglial activation. The relationship between DGM microglial activation and atrophy in MS is unknown. 

To determine the relationship between microglial activation in the deep grey matter (DGM) and both regional atrophy and physical disability in multiple sclerosis (MS).

Fourteen MS patients [age 42.2±12.8 years, 8 relapsing-remitting (RR), 6 secondary progressive (SP), Expanded Disability Status Scale (EDSS) score 3.9±2.3 (range 1-7.5); timed 25 foot walk (T25FW) 8.0±3.9 (range 4-19.4) seconds] and 8 healthy controls (HC) (age 42.5±16.3 years) underwent [F-18]PBR06 PET and 3T MRI for assessing DGM (thalamus, caudate, putamen, globus pallidus (GP)) microglial activation and atrophy, respectively. Standardized Uptake Value (SUV) PET maps were co-registered to MRI. SUV ratios (SUVRs) were global brain-normalized. The FSL-FIRST pipeline determined DGM volumes (Vols). Independent samples t-tests and Pearson’s correlations were performed. 

Thalamic SUVR was higher in SPMS vs. HC (+9.8%, p=0.03) and thalamic, putaminal and GP SUVRs were higher in SPMS vs. RRMS (+14.8%,+12.9%, +14.0%, p=0.001, 0.005, 0.01, respectively). Thalamic, putaminal and GP Vols were lower in MS vs. HC (-17.1%, -18.4%, -19.4%, p=0.003, 0.001, 0.0001, respectively), SPMS vs. HC (-16.5%, -19.1%, -20.7%, p=0.01, 0.005, 0.002, respectively) and RRMS vs. HC (-17.5%, -18.0%, -18.4%, p=0.002, 0.02, 0.002, respectively). Among MS patients, bivariate (r= -0.56, p=0.03) and age-adjusted partial (r= -0.57, p=0.04) correlations indicated that the link between structure-specific DGM microglial activation and atrophy was strongest in the GP. Thalamic (r=0.89, p=0.00002; r=0.87, p=0.00005) and putaminal (r=0.63, p=0.01; r=0.68, p=0.007) SUVRs showed significant correlations with EDSS score and T25FW.