Deep gray matter changes in relapsing-remitting multiple sclerosis detected by multi-parametric, high-resolution...

To investigate a variety of magnetic resonance imaging (MRI) quantitative metrics, which reflect different aspects of microstructural damage in deep gray matter (dGM) regions and white matter T2 lesions in patients with relapsing-remitting multiple sclerosis (RRMS), and to determine the level of pathological interconnection between these two entities as well as their association with clinical disability.

We recruited thirty RRMS patients along with thirty age-matched healthy controls (HCs). Both groups were scanned at 3 T MRI using 3D high-resolution T1-, T2-, and T2*-weighted, magnetization transfer (MT)-prepared gradient echo for MT ratio (MTR) mapping, and eight repeats of T1-weighted images acquired at different inversion times to create T1 maps. dGM structures were segmented from T1-weighted images using FreeSurfer, WM-T2 lesions were extracted from T2-weighted images, and iron maps were calculated from the phase part of the T2*-weighted sequence. Extracted dGM MRI indices were compared between both groups. In the RRMS group, dGM MRI indices were correlated with those of WM-T2 lesions, expanded disability status scale, and disease duration.

dGM volumetric metrics of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant moderate association with lesions' load (p < 0.05) and lesions' iron concentration (p < 0.01). dGM MTRs of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant (p < 0.01) moderate correlation with lesion T1 times. While T1 changes in some dGM regions of RRMS patients associated weakly with those of T2 lesions, dGM iron concentration did not show any association with any of lesions' metrics. Furthermore, lesions' MTR changes did not show any association with any dGM metrics. Most dGM metrics did not show any correlation with disease severity. Contrarily, most lesions' metrics showed weak association with disease severity.

dGM changes occur in a non-uniform pattern and, almost, do not link directly to MS disease severity. Contrarily, most WM-T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM.

• Deep gray matter (dGM) structures are very much involved in the MS disease process and quite substantial neurodegeneration is undergone during the relapsing-remitting phase of the MS disease. • Deep gray matter (dGM) quantitative changes occur in a non-uniform and non-linked pattern and, except for CN's iron deposition, do not directly associate with the MS disease severity. • Most white matter T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM structures.