Non-Gaussian water diffusion in aging white matter

Abstract

Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease.

Keywords: Aging; Diffusion tensor imaging; Diffusional kurtosis imaging; K-means clustering; MRI; Multivariate analysis; Region-of-interest analysis; Tract-based spatial statistics; White matter integrity.