Using Myelin Water Imaging to Investigate Myelin Damage and Its Association with Clinical Outcomes in Radiologically Isolated Syndrome (S27.005)

Objective: To investigate regional myelin damage and its association with clinical outcomes in people with radiologically isolated syndrome (pwRIS). Background: RIS is defined by white matter lesions characteristic of multiple sclerosis (MS) on magnetic resonance imaging (MRI) in the absence of overt clinical symptoms. Existing studies have shown that brain volume is lower in pwRIS vs healthy controls (HCs) and that high lesion volume is associated with poor cognitive performance in pwRIS. Regional myelin status and its association with clinical performance is unknown in pwRIS. Myelin water imaging (MWI) is a quantitative, biologically-specific MRI technique for assessing myelin in vivo through the myelin water fraction (MWF). Design/Methods: Twenty-seven pwRIS (mean age: 45 years, 23 females) and 20 HCs (mean age: 43 years, 14 females) underwent MWI performed at 3T. MWF was extracted from 4 regions of interest (ROIs) and compared between pwRIS and HCs using the Mann-Whitney U-test. Correlations between the MWF of each ROI and the Timed 25ft Walk (T25FW), the 9 Hole Peg Test (9HPT), and the Symbol Digit Modalities Test (SDMT) were evaluated using Pearson correlation. Results: MWF was lower in the corticospinal tract (RIS/HC: 0.207/0.230 (p=0.004)) and corpus callosum (RIS/HC: 0.102/0.119 (p=0.002)) in pwRIS compared to HCs. No significant MWF differences in the cingulum (p=0.86) or superior longitudinal fasciculus (SLF) (p=0.093) were observed. In pwRIS, T25FW performance correlated with MWF in the corticospinal tract (R=−0.53, p=0.004) and corpus callosum (R=−0.38, p=0.049). No significant correlations were observed between the 9HPT or SDMT and MWF of the corticospinal tract, corpus callosum, cingulum, or SLF. Conclusions: MWI reveals diffuse myelin damage in the cerebral white matter of pwRIS. Myelin damage in pwRIS is associated with ambulatory function in the absence of overt clinical symptoms. Longitudinal evaluation of MWI and clinical changes in pwRIS will provide early insight in the mechanisms of progression in MS. Disclosure: Mr. Keane has received research support from Faculty of Medicine at the University of British Columbia. Ms. Johnson has nothing to disclose. Dr. Lee has nothing to disclose. The institution of Dr. Tam has received research support from Natural Sciences and Engineering Research Council. The institution of Dr. Tam has received research support from Praxis Spinal Cord Institute. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD-Serono. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Oh has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from EMD-Serono. The institution of Dr. Oh has received research support from Biogen-Idec. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. The institution of Dr. Traboulsee has received research support from Roche. The institution of Dr. Traboulsee has received research support from Genzyme. Dr. Kolind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Kolind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Kolind has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Kolind has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Kolind has received research support from Sanofi Genzyme. The institution of Dr. Kolind has received research support from Roche. The institution of Dr. Kolind has received research support from Biogen.