# An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis

## TL;DR

This study uses MRI to investigate how lesions in multiple sclerosis grow or shrink, focusing on their orientation relative to brain structures like veins and white matter tracts.

## Contribution

The study introduces a tensor model to analyze lesion orientation and directional changes in MS lesions using MRI data.

## Key findings

- Lesions aligned with veins and surface-in gradients had lower volume compared to other orientations.
- Lesion expansion and contraction occurred along veins and white matter tracts, but remyelination was linked to surface-in gradients.
- Bexarotene did not affect lesion expansion or contraction but increased remyelination in specific orientations.

## Abstract

To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).

We assessed 1,613 lesions in 49 people with relapsing–remitting MS in the CCMR‐One bexarotene trial (EudraCT 2014‐003145‐99). We measured lesion orientation relative to WM tracts, surface‐in gradients and veins. Jacobian deformation was used to assess lesion expansion over 6 months, while magnetization transfer ratio (MTR) imaging was used to assess remyelination.

At baseline, 33% of lesions were aligned with veins, 2% along WM tracts, 0% with surface‐in gradients, and 4% orthogonal to veins. No significant differences were observed in lesion shape, while lesions aligned with surface‐in gradients and with veins had lower volume compared to all remaining orientations. At follow‐up, 13% of lesions expanded and 7% contracted. The directions for both expansion and contraction were 18% and 8%, respectively, along WM tracts, 20% and 15% parallel to veins, 22% and 23% orthogonal to veins and 0% and 1% along surface‐in gradients. Bexarotene had no effect on lesion expansion or contraction, but MTR significantly increased in lesions aligned with surface‐in gradients and veins.

Lesion expansion and shrinkage are affected by venous and WM tract factors, but these do not influence bexarotene's capacity to promote remyelination. This, instead, appears to be affected by surface‐in factors. To limit lesion expansion and maximize tissue repair, multiple processes may need to be targeted.

By applying the tensor model, we analysed lesion orientation and the directionality of lesion expansion/contraction in multiple sclerosis. Each lesion is summarized as an ellipsoid, and the tensor model is applied to calculate lesion anisotropy. From the top to the bottom white matter atlas, surface‐in gradient segmentation and venous atlas used in the present study are represented together with examples of lesions aligned with each orientation assessed.