Using Myelin Water Imaging to Investigate Myelin Damage and its Association with Clinical Outcomes in Radiologically Isolated Syndrome
Connor Keane1, Poljanka Johnson1, Joshua Lee2, Roger Tam3, Jiwon Oh4, Anthony Traboulsee1, Shannon Kolind1
1University of British Columbia, 2Neurology Residency Program, UBC, 3University of British Columbia, MS/MRI Research Group, 4St Michael's Hospital
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.