T-1D-weighted ihMT imaging - Part II. Investigating the long- and short-T-1D components correlation with myelin content. Comparison with R-1 and the macromolecular proton fraction

Purpose To investigate the long- and short-T-1D components correlation with myelin content using inhomogeneous magnetization transfer (ihMT) high-pass and band-pass T-1D-filters and to compare ihMT, R-1, and the macromolecular proton fraction (MPF) for myelin specific imaging. Methods The 3D ihMT rapid gradient echo (ihMTRAGE) sequences with increasing switching times (Delta t) were used to derive ihMT high-pass T-1D-filters with increasing T-1D cutoff values and an ihMT band-pass T-1D-filter for components in the 100 mu s to 1 ms range. 3D spoiled gradient echo quantitative MT (SPGR-qMT) protocols were used to derive R-1 and MPF maps. The specificity of R-1, MPF, and ihMT T-1D-filters was evaluated by comparison with two histological reference techniques for myelin imaging. Results The higher contribution of long-T(1D)s as compared to the short components as Delta t got longer led to an increase in the specificity to myelination. In contrast, focusing on the signal originating from a narrow range of short-T(1D)s (< 1 ms) as isolated by the band-pass T-1D-filter led to lower specificity. In addition, the significantly lower r(2) correlation coefficient of the band-pass T-1D-filter suggests that the origin of short-T-1D components is mostly associated with non-myelin protons. Also, the important contribution of short-T(1D)s to the estimated MPF, explains its low specificity to myelination as compared to the ihMT high-pass T-1D-filters. Conclusion Long-T-1D components imaging by means of ihMT high-pass T-1D-filters is proposed as an MRI biomarker for myelin content. Future studies should enable the investigation of the sensitivity of ihMT T-1D-filters for demyelinating processes.