Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming.

Diffusion tensor imaging (DTI) was used to examine 1) age-related changes in genu, splenium, and centrum semiovale white matter diffusivity in 64 healthy men and women (age 23-85 years); 2) the relationship between diffusivity (trace) and fractional anisotropy (FA) across and within individuals; and 3) the role of macrostructural and microstructural partial voluming effects on the DTI metrics. Regional differences were greater in FA (approximately 43%) than in trace (approximately 16%). Depending on the region of interest, trace increased with age (r = 0.24 to 0.58) and FA decreased with age (r = -0.29 to -0.79). FA was inversely correlated with trace, even when controlling for age. Histogram analysis of trace and FA following systematic expansion and dilation of the white matter regions demonstrated greater susceptibility of FA than trace to error arising from macrostructural partial voluming, i.e., erroneous inclusion of primarily nonwhite-matter voxels. Three-phase ellipsoid shape analysis revealed that after morphometric erosion the spherical component remained greater in older than younger subjects in the splenium and centrum, suggesting that age-related reduction in FA arises from intravoxel increased interstitial fluid. Reducing the size of the white matter samples to control for macrostructural partial voluming attenuated but did not negate effects, indicating that observed changes in white matter with aging can reflect real microstructural alterations rather than sampling artifact. Morphological dilation of white matter regions of interest resulting in purposeful inclusion of non-white matter pixels significantly reduced mean FA, suggesting that reports of FA values below 0.25 in healthy adults may reflect partial voluming rather than actual changes in white matter coherence.