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Updated: Jan 7, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Periventricular gradients in axonal and myelin microstructure are present in people with multiple sclerosis having
Hannah R Bernstein1,2,3, Vladimir Grouza1,2, Joseph S Gati4
1McConnell Brain Imaging Centre, The Neuro (Montreal Neurological Institute-Hospital), Montreal, QC, Canada.
Background:
MS imaging studies have demonstrated an ependymal "surface-in" distribution of white matter damage. The origin of this effect and how it impacts myelinated axons in people with MS (PwMS) is poorly understood.
Objectives:
To investigate (1) whether there is clear evidence of tract-wise, periventricular damage, based on fractional anisotropy, mean diffusivity, axonal water fraction (AWF) and myelin volume fraction (MVF), in PwMS, (2) if such tissue damage is associated with T1-"black-hole" (T1-BH) and/or non-BH lesions, and (3) if periventricular quantitative MRI abnormalities are correlated with lateral ventricle (LV) and choroid plexus (CP) enlargement.
Methods:
We applied structural, MT-weighted, and multi-shell diffusion MRI in healthy controls and PwMS to quantify periventricular gradient damage to axons and myelin. We also evaluated the correlation between such gradient damage and both non-BH and T1-BH lesion loads, and brain volume changes.
Results:
Clear periventricular gradients exist in both AWF and MVF measures in the Association and Projection Tracts. They are strongly correlated with T1-BH lesion load, and with LV and CP enlargement in PwMS with EDSS > 2.
Conclusions:
Tract-specific, periventricular gradients in PwMS exist prominently in AWF and MVF, are strongly associated with T1-BH lesion loads, and correlate with LV and CP enlargement.
Insights
Multiple Sclerosis (MS) white matter damage shows periventricular gradients in axonal water fraction (AWF) and myelin volume fraction (MVF). This damage correlates with T1-black-hole lesions and ventricle enlargement in people with MS.
Area of Science:
- Neuroimaging
- Neurodegeneration
- Multiple Sclerosis Research
Background:
- MS imaging reveals white matter damage concentrated near the ventricles.
- The origins and impact of this periventricular damage on axons in MS are not well understood.
Purpose of the Study:
- To identify tract-specific, periventricular white matter damage using MRI measures like fractional anisotropy, mean diffusivity, axonal water fraction (AWF), and myelin volume fraction (MVF) in people with MS (PwMS).
- To assess the association between this periventricular damage and T1-black-hole (T1-BH) and non-black-hole lesions.
- To investigate the correlation between periventricular MRI abnormalities and enlargement of the lateral ventricles (LV) and choroid plexus (CP).
Main Methods:
- Utilized structural, MT-weighted, and multi-shell diffusion MRI in healthy controls and PwMS.
- Quantified periventricular gradients in axonal and myelin damage.
- Correlated gradient damage with non-BH and T1-BH lesion loads and brain volume changes.
Main Results:
- Identified distinct periventricular gradients in AWF and MVF within Association and Projection Tracts.
- Found strong correlations between these gradients and T1-BH lesion load.
- Observed significant associations with LV and CP enlargement in PwMS with an Expanded Disability Status Scale (EDSS) score greater than 2.
Conclusions:
- Tract-specific, periventricular gradients in AWF and MVF are prominent in PwMS.
- These gradients are strongly linked to T1-BH lesion loads.
- Periventricular abnormalities correlate with lateral ventricle and choroid plexus enlargement.
