MRI Analysis of White Matter Myelin Water Content in Multiple Sclerosis: A Novel Approach Applied to Finding Correlates of Cortical Thinning.

A novel lesion-mask free method based on a gamma mixture model was applied to myelin water fraction (MWF) maps to estimate the association between cortical thickness and myelin content, and how it differs between relapsing-remitting (RRMS) and secondary-progressive multiple sclerosis (SPMS) groups (135 and 23 patients, respectively). It was compared to an approach based on lesion masks. The gamma mixture distribution of whole brain, white matter (WM) MWF was characterized with three variables: the mode (most frequent value) m1 of the gamma component shown to relate to lesion, the mode m2 of the component shown to be associated with normal appearing (NA) WM, and the mixing ratio (λ) between the two distributions. The lesion-mask approach relied on the mean MWF within lesion and within NAWM. A multivariate regression analysis was carried out to find the best predictors of cortical thickness for each group and for each approach. The gamma-mixture method was shown to outperform the lesion-mask approach in terms of adjusted R2, both for the RRMS and SPMS groups. The predictors of the final gamma-mixture models were found to be m1 (ß = 1.56, p < 0.005), λ (ß = -0.30, p < 0.0005) and age (ß = -0.0031, p < 0.005) for the RRMS group (adjusted R2 = 0.16), and m2 (ß = 4.72, p < 0.0005) for the SPMS group (adjusted R2 = 0.45). Further, a DICE coefficient analysis demonstrated that the lesion mask had more overlap to an ROI associated with m1, than to an ROI associated with m2 (p < 0.00001), and vice versa for the NAWM mask (p < 0.00001). These results suggest that during the relapsing phase, focal WM damage is associated with cortical thinning, yet in SPMS patients, global WM deterioration has a much stronger influence on secondary degeneration. Through these findings, we demonstrate the potential contribution of myelin loss on neuronal degeneration at different disease stages and the usefulness of our statistical reduction technique which is not affected by the typical bias associated with approaches based on lesion masks.

T2 prep three-dimensional spiral imaging with efficient whole brain coverage for myelin water quantification at 1.5 tesla.

Quantitative assessment of myelination is important for characterizing tissue damage and evaluating response to therapy in white matter diseases such as multiple sclerosis. Conventional multicomponent T(2) relaxometry based on the two-dimensional (2D) multiecho spin echo sequence is a promising method to measure myelin water fraction, but its clinical utility is impeded by the prohibitively long data acquisition and limited brain coverage. The objective of this study was to develop a signal-to-noise ratio efficient 3D T(2) prep spiral gradient echo (3D SPIRAL) sequence for full brain T(2) relaxometry and to validate this sequence using 3D multiecho spin echo as reference standard in healthy brains at 1.5 T. 3D SPIRAL was found to provide similar myelin water fraction in six selected white and gray matter areas using region-of-interest signal averaging analysis (N = 7, P > 0.05). While 3D multiecho spin echo only provided partial brain coverage, 3D SPIRAL enabled whole brain coverage with a fivefold higher acquisition speed per imaging slice and similar signal-to-noise ratio efficiency. Both 3D sequences provided superior signal-to-noise ratio efficiency when compared to the conventional 2D multiecho spin echo approach.