The goal of this study was to investigate how the angular dispersion of axonal fibers changes during the course of healthy aging. The angular dispersion was derived from the fiber orientation density function (fODF), which was estimated in vivo with a diffusion MRI technique called fiber ball imaging. Intra-voxel angular dispersion of axonal fibers within the corpus callosum at the midline up to the anterior tip of the frontal horn of the lateral ventricles was quantified for a cohort of 63 healthy older adults (ages 45 to 85 years). The splenium, body, and genu of the corpus callosum were examined separately, and fODFs within each of these regions were averaged across voxels to obtain three mean fODFs for each study participant. For all three regions, we found that the angular dispersion, as quantified by the full width of the mean fODF at half its maximum, decreases significantly with age. However, these decreases were not significantly different across the regions. In addition, the heights of the mean fODF peaks increase with age. This reduction in angular dispersion and increase in height imply axons with orientations deviating further from the fODF peak are more likely to be lost in the course of healthy aging. We propose that this is related to the known preferential loss of thinner myelinated axons with increasing age.

Intercellular water exchange in brain is analyzed in terms of the multi-compartment Kärger model (KM), and the mean KM water exchange rate is used as a summary statistic for characterizing the exchange processes. Prior work is extended by deriving a stronger lower bound for mean exchange rate that can be determined from the time dependence of the diffusional kurtosis. In addition, an analytic formula giving the time dependence of the kurtosis for a model of thin cylindrical neurites is demonstrated, and this formula is applied to numerically test the accuracy of the lower bound for a range of model parameters. Finally, the lower bound is measured in vivo with diffusional kurtosis imaging for the dorsal hippocampus and cerebral cortex of 8-month-old mice. From the stronger lower bound, the mean KM exchange rate is found to be 46.1 ± 11.0 s -1 or greater in dorsal hippocampus and 20.5 ± 8.5 s -1 or greater in cortex.