Fig 5 presents voxel-wise correlations of age with several parameters modeled from the dMRI data (along the centers of the main white matter tracts), as well as normalized T2 FLAIR intensity in the white matter. Fractional anisotropy (FA), a sensitive but non-specific marker of white matter integrity, predominantly demonstrates the established reduction of FA with aging (Fig 5a,g). However, some voxels exhibit the opposite, of FA increasing with aging, which may reflect degradation of secondary fibers or reduced fiber dispersion23; notably, none of the FA-based IDPs exhibit this significant positive correlation, demonstrating that averaging across tracts can sacrifice richness of information. The tensor mode24 (Fig 5b), which primarily describes whether a voxel contains one vs. multiple tracts, was even more sensitive with highly significant positive correlations in certain association fiber areas and posterior corpus callosum (arrows), likely the same effect seen as FA increases23. We further observed an increase in free water with aging (Fig 5d); the strongest increase, in the fornix (arrow), is likely due to an increase of the fraction of CSF within voxels spanning this thin tract
