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Updated: Feb 25, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring
A Hagiwara1,2, M Hori3, K Yokoyama4
1From the Departments of Radiology (A.H., M. Hori., M.N., R.U., M. Horita, C.A., S.A.) a-hagiwara@juntendo.ac.jp.
Background And Purpose:
Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique.
Materials And Methods:
Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM.
Results:
All metrics differed significantly across the 3 groups (P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio (P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction).
Conclusions:
In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS.
Insights
In multiple sclerosis (MS), myelin damage in white matter (WM) is more severe than axonal damage, as shown by novel MRI metrics. These metrics may help assess WM injury in MS patients.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Neurology
Background:
- Myelin and axon volume fractions, and g-ratio, are novel MRI-derived metrics.
- These metrics allow in vivo estimation of nerve fiber integrity.
- Previous methods for assessing white matter (WM) damage in multiple sclerosis (MS) have limitations.
Purpose of the Study:
- To evaluate WM damage in MS patients using advanced in vivo MRI techniques.
- To compare myelin and axon damage in different WM regions of MS patients.
- To assess the utility of myelin and axon volume fractions and g-ratio in characterizing MS-related WM pathology.
Main Methods:
- Analyzed 149 chronic plaques in 20 relapsing-remitting MS patients.
- Calculated myelin volume fraction using simultaneous tissue relaxometry.
- Quantified intracellular and CSF compartment volume fractions via neurite orientation dispersion and density imaging.
- Derived axon volume fraction and g-ratio by combining these measurements.
- Measured metrics in plaques, periplaque WM, and normal-appearing WM.
Main Results:
- Significant differences in all metrics were observed across plaques, periplaque WM, and normal-appearing WM (P < .001).
- Myelin volume fraction showed greater percentage changes in plaques and periplaque WM compared to axon volume fraction and g-ratio.
- Myelin damage was more pronounced than axonal damage in MS lesions.
Conclusions:
- In MS patients, myelin is more severely damaged than axons in both plaques and periplaque WM.
- Myelin and axon volume fractions and g-ratio show potential as biomarkers for evaluating WM damage in MS.
- This study highlights the utility of advanced MRI techniques for quantifying neurodegeneration in MS.

