Spatiotemporal alterations of gray matter microstructure in newly diagnosed relapsing-remitting multiple sclerosis patients: A longitudinal diffusion kurtosis MRI study

Background: In multiple sclerosis (MS), neurodegeneration occurs in both white matter (WM) and gray matter (GM). Altered GM microstructure, estimated using magnetic resonance imaging (MRI), correlates with clinical disability and demyelinating WM lesions. Therefore, MRI measurements of GM microstructure may be an early biomarker in MS. Objectives: The study aims to investigate the association between the microstructural characteristics of cortical and subcortical GM and clinical disability in newly diagnosed patients with relapsing-remitting MS (RRMS). Secondarily, the study investigates potential longitudinal alterations of tissue microstructure in relation to clinical disability and changes in WM lesion volume. Methods: Eighty-two newly diagnosed RRMS patients were physically and cognitively tested and brain scanned using structural and diffusion kurtosis MRI at baseline and after 48 weeks. Results: At baseline, WM lesion volume correlated with mean diffusivity (MD) in cortex, thalamus (r2 = 0.52), caudate (r2 = 0.40) and putamen (r2 = 0.37), and with thalamus volume (r2 = 0.67). Longitudinally, increased lesion volume from baseline to 48 weeks was associated with a spatiotemporal increase in cortical MD. Conclusions: The microstructure of cortical and subcortical GM is associated with both the degree and change of lesion volume in patients with RRMS. Diffusion MRI could serve as a surrogate measure of WM injury and longitudinal neurodegeneration in MS.