Objectives Conventional MRI is not sensitive to many pathological processes underpinning multiple sclerosis (MS) ongoing in normal appearing brain tissue (NABT). Quantitative MRI (qMRI) and a multiparameter mapping (MPM) protocol are used to simultaneously quantify magnetization transfer (MT) saturation, transverse relaxation rate R2* (1/T2*) and longitudinal relaxation rate R1 (1/T1), and assess differences in NABT microstructure between MS patients and healthy controls (HC). Methods This prospective cross-sectional study involves 36 MS patients (21 females, 15 males; age range 22–63 years; 15 relapsing-remitting MS - RRMS; 21 primary or secondary progressive MS - PMS) and 36 age-matched HC (20 females, 16 males); age range 21–61 years). The qMRI maps are computed and segmented in lesions and 3 normal appearing cerebral tissue classes: normal appearing cortical grey matter (NACGM), normal appearing deep grey matter (NADGM), normal appearing white matter (NAWM). Individual median values are extracted for each tissue class and MR parameter. MANOVAs and stepwise regressions assess differences between patients and HC. Results MS patients are characterized by a decrease in MT, R2* and R1 within NACGM ( p < .0001) and NAWM ( p < .0001). In NADGM, MT decreases ( p < .0001) but R2* and R1 remain normal. These observations tend to be more pronounced in PMS. Quantitative MRI parameters are independent predictors of clinical status: EDSS is significantly related to R1 in NACGM and R2* in NADGM; the latter also predicts motor score. Cognitive score is best predicted by MT parameter within lesions. Conclusions Multiparametric data of brain microstructure concord with the literature, predict clinical performance and suggest a diffuse reduction in myelin and/or iron content within NABT of MS patients.
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.
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