Open Collections

Kalau, Olivia

University of British Columbia

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that results in characteristic discrete lesions visible on conventional magnetic resonance imaging (MRI), and diffuse damage to the surrounding normal appearing white matter (NAWM). Clinically, MS presents with a wide range of symptoms which often include cognitive impairment (CI), of which processing speed is commonly implicated. Improving our understanding of the biological basis of MS-related CI and future cognitive performance may help to uncover relevant biomarkers and provide opportunities to target these symptoms at earlier stages. People with radiologically isolated syndrome (RIS) can convert to MS and can present with CI patterns similar to MS. Thus, RIS represents a unique opportunity to explore the evolution of CI and associations with early disease biomarkers. Myelin water imaging (MWI) is a histologically validated advanced MRI technique capable of measuring myelin content. From MWI scans, the mean myelin water fraction (MWF) and standard deviation (SD) within a region of interest can be extracted, and the myelin heterogeneity index (MHI) can be calculated (MHI = SD/mean MWF). Here, we used MWI as a biomarker to explore myelin differences in NAWM of people with RIS compared to neurologically healthy controls and investigate the relationship between MWI metrics and processing speed. We detected NAWM myelin damage in RIS, particularly in the corpus callosum, and found that increased NAWM myelin damage, particularly in the cingulum, was associated with slower processing speed in RIS. Additionally, we used MWI to explore longitudinal changes in processing speed in people with MS. In people with progressive MS, lower baseline NAWM MHI, indicative of less myelin damage, was associated with a greater decline in processing speed over time. Overall, these results demonstrate the utility of MWI as a biomarker of myelin specific pathology relevant to clinical symptoms and highlights the complexity of MS-related CI across the spectrum of MS.

Text

2024-08-27

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89038

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/