The myelin water fraction and magnetization transfer ratio are useful markers of remyelination, according to a new study published in Brain Pathology. Moreover, measurements derived from diffusion tensor imaging may help measure myelin in the brains of patients with multiple sclerosis (MS).

In addition, the researchers identified extensive astrogliosis in all lesions, even after remyelination, suggesting a potential role of astrocytes in the regeneration of myelin.

The aim of the study was to identify quantitative magnetic resonance imaging (qMRI) measurements that could distinguish between lesion types in postmortem brains of patients with MS and to shed light on the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes.


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The researchers imaged 3 fixed MS whole brains using qMRI at 3T to obtain the magnetization transfer ratio, myelin water fraction, quantitative T1 and susceptibility mapping, fractional anisotropy, and radial diffusivity maps. Then, using histological staining methods, immunohistochemistry, and immunofluorescence, the team identified the lesion type and quantified the tissue components.

The results showed that the magnetization transfer ratio and myelin water fraction best predicted the chance of a lesion being remyelinated. Radial diffusivity and quantitative susceptibility mapping, on the other hand, could distinguish active lesions. 

Microstructural properties as measured by qMRI did not show any difference between chronic active and inactive lesions. 

Myelin water fraction and radial diffusivity were associated with myelin content in both lesions and white matter that appeared normal.

The measures most associated with axon content and astrocyte immunoreactivity were fractional anisotropy and myelin water fraction, respectively. The latter was only associated with astrocyte immunoreactivity in the lesions, while the former was associated with axon content in both lesions and normal-appearing white matter. 

“Our study provides new information on the discriminative power of qMRI in differentiating MS lesions—especially remyelinated ones—as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes,” the researchers concluded. 

Reference

Galbusera R, Bahn E, Weigel M, et al. Postmortem quantitative MRI disentangles histological lesion types in multiple sclerosis. Brain Pathol. Published online December 8, 2022. doi:10.1111/bpa.13136