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

Abstract

Objective

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

Methods

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.

Results

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.

Interpretation

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.