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Updated: Feb 25, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Global loss of myelin water over 5 years in multiple sclerosis normal-appearing white matter
Irene M Vavasour1, Sophie C Huijskens2, David Kb Li3
1Department of Radiology, The University of British Columbia, Vancouver, BC, Canada.
Background:
Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T2 (ieGMT2, reflecting intra/extracellular water properties), and increased T1 (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM).
Objective:
To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM.
Methods:
A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2-5.8 years) with a 32-echo T2 relaxation and an inversion recovery T1 sequence. For every voxel, MWF, ieGMT2, and T1 were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined.
Results:
In MS subjects, NAWM MWF mean decreased by 8% ( p = 0.0016). No longitudinal changes were measured in T1 or ieGMT2. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric.
Conclusion:
The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years.
Insights
Longitudinal MRI in multiple sclerosis (MS) shows myelin water fraction (MWF) decreases in normal-appearing white matter (NAWM) over time. This indicates progressive myelin damage occurs over many years in the MS brain.
Area of Science:
- Neuroimaging
- Neuroscience
- Medical Physics
Background:
- Cross-sectional studies show reduced myelin water fraction (MWF), increased geometric mean T2 (ieGMT2), and increased T1 in multiple sclerosis (MS) normal-appearing white matter (NAWM).
- These metrics reflect myelin integrity, water properties, and total water content, respectively.
Purpose of the Study:
- To evaluate longitudinal changes in magnetic resonance (MR) measures within the NAWM of patients with relapsing-remitting MS (RRMS).
Main Methods:
- 11 RRMS patients and 4 controls underwent 3T MRI scans at baseline and long-term follow-up (3.2-5.8 years).
- 32-echo T2 relaxation and inversion recovery T1 sequences were used to calculate MWF, ieGMT2, and T1 for each voxel.
- NAWM histogram-based metrics (mean, peak height, peak location) were analyzed.
Main Results:
- MS subjects exhibited an 8% decrease in NAWM MWF mean (p=0.0016) over the follow-up period.
- No significant longitudinal changes were observed for T1 or ieGMT2 in MS subjects.
- Control white matter showed no significant changes in any measured MR metric over time.
Conclusions:
- The observed decrease in MWF suggests ongoing, diffuse myelin damage and loss in the MS brain over extended periods.
- These findings highlight that chronic, progressive myelin damage is an evolving process in MS, occurring over many years.
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