Myelin Signal Isolated MRI (siMRI): A Novel Technique to Quantify Myelin Integrity Reveals Loss of Brain Architectonics in Multiple Sclerosis

Background: The devastating symptomology of multiple sclerosis (MS) is often uncorrelated with the disease depicted by magnetic resonance imaging (MRI) of pathological white matter, commonly known as plaques or lesions. These plaques are believed to represent inflammatory foci in the brain where demyelination events are predominant. However, minor dysregulations in myelin quality can cause axonal asynchrony and cortical impairment that precede complete demyelination represented by these plaques.

Objectives: The goal of this study was to develop a novel metric for quantifying the myeloarchitecture of MS brains, which we refer to as signal isolated MRI (siMRI) that can then be examined for its association with disease severity, symptomatology, and quality of life.

Methods: MRI data, including myelin-based siMRI and diffusion imaging, were acquired from 16 volunteers with MS and 21 normal aging adults. The regional analysis was performed for two sets of white matter tissue: i) ROIs were defined in deep, peripheral or lesion rim areas to quantify myelin compaction in plaques, and ii) ROIs were additionally defined across “normal-appearing” structural areas masked to the presence of plaques; whole brain histogram of myelin compaction was computed for these ROIs.

Results: Compared with normal aging adults, we observed a decline in the myeloarchitecture of those with MS. The maximum myelin compaction index measured in the tail-end of the histograms quantitatively provided evidence for a global reduction in myelin compaction, such that there was a critical decrease in myelin integrity compared with the normal aging population. Extraordinarily, the plaques seem to delineate areas with highly compact – potentially either newly redundant myelin or fibrotic fibers.

Conclusions: Altogether, myelin siMRI contributes to the evolving literature focusing on global, subpathologic myelin changes that occur in MS but are poorly understood. Assessment of myelin health using siMRI illuminates potential new targets of pathology in living patients and redirect research towards non-ablative myelin damage that is broadly prevalent in white matter of the MS brain.