Local Diffusion Homogeneity (LDH): An Inter-Voxel Diffusion MRI Metric for Assessing Inter-Subject White Matter Variability

Many diffusion parameters and indices (e.g., fractional anisotropy [FA] and mean diffusivity [MD]) have been derived from diffusion magnetic resonance imaging (MRI) data. These parameters have been extensively applied as imaging markers for localizing white matter (WM) changes under various conditions (e.g., development, degeneration and disease). However, the vast majority of the existing parameters is derived from intra-voxel analyses and represents the diffusion properties solely within the voxel unit. Other types of parameters that characterize inter-voxel relationships have been largely overlooked. In the present study, we propose a novel inter-voxel metric referred to as the local diffusion homogeneity (LDH). This metric quantifies the local coherence of water molecule diffusion in a model-free manner. It can serve as an additional marker for evaluating the WM microstructural properties of the brain. To assess the distinguishing features between LDH and FA/MD, the metrics were systematically compared across space and subjects. As an example, both the LDH and FA/MD metrics were applied to measure age-related WM changes. The results indicate that LDH reveals unique inter-subject variability in specific WM regions (e.g., cerebral peduncle, internal capsule and splenium). Furthermore, there are regions in which measurements of age-related WM alterations with the LDH and FA/MD metrics yield discrepant results. These findings suggest that LDH and FA/MD have different sensitivities to specific WM microstructural properties. Taken together, the present study shows that LDH is complementary to the conventional diffusion-MRI markers and may provide additional insights into inter-subject WM variability. Further studies, however, are needed to uncover the neuronal mechanisms underlying the LDH.