Abstract

Despite robust postmortem evidence and potential clinical importance of gray matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging. This prospective cross‐sectional study aimed at characterizing the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI (qMRI) parameters—magnetization transfer (MT) saturation, longitudinal (R1), and effective transverse (R2*) relaxation rates, derived from data acquired during a single scanning session. Our study involved 35 MS patients (14 relapsing–remitting MS; 21 primary or secondary progressive MS) and 36 age‐matched healthy controls (HC). The qMRI maps were computed and segmented in different tissue classes. Voxel‐based quantification (VBQ) and voxel‐based morphometry (VBM) statistical analyses were carried out using multiple linear regression models. In MS patients compared with HC, three configurations of GM microstructural/volumetric alterations were identified. (a) Co‐localization of GM atrophy with significant reduction of MT, R1, and/or R2*, usually observed in primary cortices. (b) Microstructural modifications without significant GM loss: hippocampus and paralimbic cortices, showing reduced MT and/or R1 values without significant atrophy. (c) Atrophy without significant change in microstructure, identified in deep GM nuclei. In conclusion, this quantitative multiparametric voxel‐based approach reveals three different spatially‐segregated combinations of GM microstructural/volumetric alterations in MS that might be associated with different neuropathology.

Highlights

  • Despite robust post-mortem evidence and potential clinical importance of grey matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging.Our aim is to characterize the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI parameters: magnetization transfer (MT) saturation, longitudinal (R1) and effective transverse (R2*) relaxation rates

  • MRI acquisitions included a multi-parameter mapping (MPM) protocol, consisting of 3 co-localized 3D multi-echo FLASH acquisitions (MT, PD- and T1-weighted contrasts,1x1x1 mm3 resolution) and additional calibration sequences to correct for inhomogeneities in the RF transmit and B0 field

  • For the MS patients, a preliminary lesion mask was derived from the FLAIR image using the LST toolbox [3] the quantitative MRI (qMRI)'s were segmented and normalized in MNI space with the US-withLesion toolbox [4]

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Summary

Introduction

Despite robust post-mortem evidence and potential clinical importance of grey matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging.Our aim is to characterize the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI (qMRI) parameters: magnetization transfer (MT) saturation, longitudinal (R1) and effective transverse (R2*) relaxation rates.

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