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Abstract Details

Microglial Activation in the Deep Grey Matter is Associated with Regional Atrophy and Physical Disability in Multiple Sclerosis
Multiple Sclerosis
S12 - Progressive Multiple Sclerosis (1:22 PM-1:33 PM)
003

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.

Increased DGM microglial activation can be detected in patients with MS and is associated with regional atrophy and physical disability. 
Authors/Disclosures
Rohit Bakshi, MD, FAAN
PRESENTER
Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.
Tarun Singhal, MD (Brigham And Women's Hospital) Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Singhal has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana LifeSciences. The institution of Dr. Singhal has received research support from Novartis. The institution of Dr. Singhal has received research support from Department of Defense. The institution of Dr. Singhal has received research support from Foundation for Neurologic Diseases.
Steven Cicero, BS Steven Cicero has nothing to disclose.
Renxin Chu (Brigham & Women's Hospital) Dr. Chu has nothing to disclose.
Shipra Dubey Shipra Dubey has nothing to disclose.
No disclosure on file
Shahamat Tauhid, MD (Brigham & Women's Hospital) Dr. Tauhid has nothing to disclose.
No disclosure on file
Howard L. Weiner, MD (Brigham and Women'S Hospital) Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..