Is diffusion anisotropy an accurate monitor of myelination? Correlation of multicomponent T2 relaxation and diffusion tensor anisotropy in human brain.

We compare T2-relaxation and diffusion tensor data from normal human brain. The relationships between myelin-water fraction (MWF) and various diffusion tensor measures [e.g., fractional anisotropy (FA), perpendicular diffusivity (ADC perpendicular) and mean diffusivity <D>] in white matter (WM) and gray matter (GM) structures in the brain were examined in 16 normal volunteers at 1.5 T and 6 normal subjects at 3.0 T and mean diffusivity. We found some degree of linear correlation between these measurements, but by using region of interest (ROI)-based analysis, we also observed several structures which seemed to deviate significantly from a linear relationship. From all investigated relationships between various diffusion tensor measures and myelin-water content, FA and ADC perpendicular yielded the highest correlation coefficients with MWF. However, diffusion anisotropy was also significantly influenced by factors other than myelin-water content. The less operator-dependent voxel-based analysis (VBA) between myelin-water and diffusional anisotropy measures is proposed as an innovative alternative to ROI-based analysis. We confirmed that WM structures, in general, have higher diffusional anisotropy than GM structures and also have higher myelin-water content. However, our findings suggest that in the highly organized fibre arrangement of compact WM structures such as the genu of the corpus callosum, elevated degrees of diffusional anisotropies are measured, which do not necessarily correspond to an elevated myelin content but more likely reflect the highly organized directionality of fibre bundles in these areas (low microscopic and macroscopic tortuosity) as well as strongly restricted diffusion in the interstitial space between the myelinated axons. Conversely, in structures with disorganized fibre bundles and multiple fibre crossings, such as the minor and major forceps, low FA values were measured, which does not necessarily reflect a decrease myelin-water content.