Alterations in the myelination and iron distribution of the cerebral cortex underlie abnormal cortical function in multiple sclerosis (MS). Due to the pathology, the transition from the inner layers to the outer layers (from white matter to the pial surface) of the cortex reflects changes in the cyto- and myeloarchitecture of the cortex. Cortical demyelination and iron deposition are relevant aspects of tissue damage and microstructural changes may affect each layer in the cortex differently.
The purpose of this study was to assess the distribution of quantitative MRI (qMRI) measurements on the whole cortex and its sensitivity as clinically accessible biomarkers of grey matter (GM) pathology in MS.
45 participants with MS underwent 7T MRI of the brain. Magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) was processed for T1-weighted (T1w) images and a T1-map. Multi-echo gradient echo images were processed for quantitative susceptibility (χ) and R2* mapping. Cortical GM volumes were segmented into nine cortical layers and relaxometry metrics were calculated within layers. The layers were grouped in three regions, inner (0-30%), middle (31-70%) and outer region (71-100%), and the distributions of these relaxometry metrics throughout the cortical thickness were compared to collect disability scales.
Significant Spearman correlations were found with Expanded Disability Status Scale (EDSS) for the slope of the linear regression of the median values in the inner region (T1: r = -0.587, p < 0.001; R2*: r = 0.610, p < 0.001; χ: r = 0.416, p < 0.010). With timed 25-foot walk (T25FW) (T1: r = -0.429, p < 0.010; R2*: r = 0.558, p < 0.001). With symbol digit modalities test (SDMT), middle region (T1: r = -0.389, p < 0.010; R2*: r = -0.328, p < 0.050; χ: r = -0.301, p < 0.050). With EDSS, outer region (R2*: r = -0.312, p < 0.050).
Cortical layer 7T qMRI analyses revealed pattern-specific distributions and regional relationships with disability in MS. These associations might show the increase in homogeneous myelin distribution and heterogeneous iron distribution locally throughout the cortical thickness. The strong relationships found between disability scales warrant further exploration as a novel outcome measure.