Age- and gender-related changes in the normal human brain using hybrid diffusion imaging (HYDI)

Diffusion tensor imaging has been widely used to study brain diseases, disorders, development, and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b values. Further, the water diffusion in biological tissues appears biexponential, although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study 52 healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b values ranging from 0 to 9375 s/mm(2). Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole-brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel-based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability and mean-squared displacement), biexponential diffusion (i.e., volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The biexponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f(1), D(1), and D(a)) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (P(0), D(2), and D(r)). The biexponential volume fraction, f(1), showed the most widespread age dependence in the voxel-based analyses, although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline.