Imaging Poster Presentation

P0597 - Lesional myelin repair, as measured with positron emission tomography, effectively protects the integrity of surrounding tissues (ID 1889)

Speakers
  • V. Ricigliano
Authors
  • V. Ricigliano
  • M. Tonietto
  • E. Poirion
  • B. Stankoff
  • B. Bodini
Presentation Number
P0597
Presentation Topic
Imaging

Abstract

Background

In multiple sclerosis (MS), pathological changes are not limited to lesions, but extensively involve normal-appearing tissues, being more pronounced in perilesions. Histological studies have shown that the pathological changes affecting perilesions mainly result from the ongoing damage in demyelinating lesions. Similarly, the structural integrity of perilesions could depend on the extent of myelin repair at the lesional level, which can be explored in vivo by positron emission tomography (PET) with 11C-PiB.

Objectives

To assess in a longitudinal study whether myelin content changes in white matter lesions, measured with 11C-PiB PET, influence the microstructural integrity of the surrounding perilesions over time, explored by diffusion tensor imaging and magnetization transfer (MT)-derived metrics.

Methods

Nineteen patients with MS underwent a longitudinal PET/MRI study. Voxel-wise maps of 11C-PiB distribution volume ratio, reflecting myelin content, were used to calculate for each patient in each non-enhancing lesion 3 indices of myelin content change: the percentage of demyelinated voxels at baseline, and the percentage of demyelinating and remyelinating voxels over the follow-up. From each 3 mm-thick perilesional area surrounding lesions, the change over time (delta) of fractional anisotropy (FA), mean diffusivity (MD) and MT ratio (MTR), reflecting microstructural damage, was calculated. Associations between the indices of myelin content change and the delta FA, MD, and MTR in perilesions were assessed using multivariate linear regressions. Perilesions were classified in “improving” or “worsening” according to the sign of the change of the microstructural parameters and a multivariate logistic regression was used to test which PET-derived index was independently associated with perilesion class.

Results

A higher percentage of demyelinated voxels at baseline and of demyelinating voxels over the follow-up inside lesions were associated with a more severe microstructural damage developing over time in perilesions (p<0.001). Conversely, a higher percentage of remyelinating lesional voxels correlated with a more preserved perilesional microstructure at the follow-up (p<0.001). The percentage of remyelinating voxels inside lesions was the only independent predictor of perilesion improvement (p=0.001). We found that at least 43% of the demyelinated volume had to remyelinate to predict a favorable evolution of the microstructure of perilesional tissue (AUC=0.8).

Conclusions

Lesional remyelination effectively protects the integrity of surrounding tissues over time, possibly by reducing the extent of Wallerian degeneration and rescuing damaged axons.

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