It can therefore be used to visualize axonal pathways. The MR signal is reduced when water is diffusing,33 and it is possible to design an MRI protocol whose signals are depleted by water diffusing in a particular direction (a diffusion gradient image). By measuring diffusion in a large set of different directions (at least 6, but often as many as 30 to 256 directions), we can identify the primary directions of water diffusion in each voxel in the brain. Diffusion tensor imaging (DTI) models water diffusion at each voxel as an ellipsoid or “tensor,” Inhibitors,research,lifescience,medical after which tractography may be used to follow and reconstruct the major white matter fiber bundles. HARD I is similar to DTI, but

can map crossing fibers better, as Inhibitors,research,lifescience,medical it does not rely on the assumption that there is only one dominant fiber present in each voxel.34 HARDI collects diffusion information from more angles and uses orientation distribution functions (ODFs), or other spherical functions—instead of tensors—to map the probability of water diffusion in every direction, leading to more accurate tractography.35-40 Fractional anisotropy (FA), the degree

to which water diffuses in one direction (along the axon), is one of the most widely used measures of axonal integrity. As a rule of thumb—which has many exceptions—higher FA and lower mean diffusivity (MD) tend to reflect more highly developed, more strongly myelinated tracts, with a higher axonal conduction speed. These measures Inhibitors,research,lifescience,medical are reproducible in children, providing reliable developmental biomarkers.41 Specifically examining the frontal lobe white matter, Klingberg et al found significantly greater white matter fractional anisotropy in adults than in children.42 They attributed this to a lesser degree of myelination Inhibitors,research,lifescience,medical in children; Inhibitors,research,lifescience,medical this is also consistent with visual inspection of brain MRI scans from infants, which often show limited white-matter

contrast in poorly myelinated regions. Schmithorst et al expanded on earlier work, examining a range of specific tracts in subjects between 5 and 18 years old.43 FA increased with age in the internal capsule, corticospinal tract, left arcuate fasciculus, and right inferior longitudinal fasciculus. Similar trajectories have been reported in DTI studies of the entire lifespan.44 In one study, FA increased with age in the internal capsule, the white matter of the prefrontal cortex, corpus callosum, basal ganglia and thalamic pathways, and visual pathways.45 Several of these regions underlie cognitive functions such as memory GSK-3 and attention, as well as motor skills. Eluvathingal et al examined 6 specific tracts and found three patterns in the results.46 Various parts of the arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and corticospinal tract showed either increased in FA with decreases in other measures of diffusivity, or no detectable effect on FA and decreases in diffusivity.