Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation.

ABSTRACT

PURPOSE: We investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo-derived myelin water fraction (MWF). METHODS: We measured the three metrics in 17 white and three deep grey matter regions in 17 healthy adults at 3 T. RESULTS: We found a strong correlation between ihMTR and MTR (r = 0.70, p < 0.001) and ihMTR and MWF (r = 0.79, p < 0.001), and a weaker correlation between MTR and MWF (r = 0.54, p < 0.001). The dynamic range in white matter was greatest for MWF (2.0%-27.5%), followed by MTR (14.4%-23.2%) and then ihMTR (1.2%-5.4%). The average scan-rescan coefficient of variation for white matter regions was 0.6% MTR, 0.3% ihMTR, and 0.7% MWF in metric units; however, when adjusted by the dynamic range, these became 6.3%, 6.1% and 2.8%, respectively. All three metrics varied with fiber direction MWF and ihMTR were lower in white matter fibers perpendicular to B0 by 6% and 1%, respectively, compared with those parallel, whereas MTR was lower by 0.5% at about 40°, with the highest values at 90°. However, separating the apparent orientation dependence by white matter region revealed large dissimilarities in the trends, suggesting that real differences in myelination between regions are confounding the apparent orientation dependence measured using this method. CONCLUSION: The strong correlation between ihMTR and MWF suggests that these techniques are measuring the same myelination; however, the larger dynamic range of MWF may provide more power to detect small differences in myelin.