T1D -weighted ihMT imaging - Part II. Investigating the long- and short-T1D components correlation with myelin content. Comparison with R1 and the macromolecular proton fraction

Abstract

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, R₁ , and the macromolecular proton fraction (MPF) for myelin specific imaging.

Methods: The 3D ihMT rapid gradient echo (ihMTRAGE) sequences with increasing switching times (Δt) 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 µs to 1 ms range. 3D spoiled gradient echo quantitative MT (SPGR-qMT) protocols were used to derive R₁ and MPF maps. The specificity of R₁ , 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 Δt 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 r² 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.

Keywords: ihMT T1D-filtering; long-T1D components; myelin microscopy imaging; myelin specificity; short-T1D components.