Diffusion time dependency along the human corpus callosum and exploration of age and sex differences as assessed by...

Conventional diffusion imaging uses pulsed gradient spin echo (PGSE) waveforms with diffusion times of tens of milliseconds (ms) to infer differences of white matter microstructure. The combined use of these long diffusion times with short diffusion times (<10 ​ms) enabled by oscillating gradient spin echo (OGSE) waveforms can enable more sensitivity to changes of restrictive boundaries on the scale of white matter microstructure (e.g. membranes reflecting the axon diameters). Here, PGSE and OGSE images were acquired at 4.7 ​T from 20 healthy volunteers aged 20-73 years (10 males). Mean, radial, and axial diffusivity, as well as fractional anisotropy were calculated in the genu, body and splenium of the corpus callosum (CC). Monte Carlo simulations were also conducted to examine the relationship of intra- and extra-axonal radial diffusivity with diffusion time over a range of axon diameters and distributions. The results showed elevated diffusivities with OGSE relative to PGSE in the genu and splenium (but not the body) in both males and females, but the OGSE-PGSE difference was greater in the genu for males. Females showed positive correlations of OGSE-PGSE diffusivity difference with age across the CC, whereas there were no such age correlations in males. Simulations of radial diffusion demonstrated that for axon sizes in human brain both OGSE and PGSE diffusivities were dominated by extra-axonal water, but the OGSE-PGSE difference nonetheless increased with area-weighted outer-axon diameter. Therefore, the lack of OGSE-PGSE difference in the body is not entirely consistent with literature that suggests it is composed predominantly of axons with large diameter. The greater OGSE-PGSE difference in the genu of males could reflect larger axon diameters than females. The OGSE-PGSE difference correlation with age in females could reflect loss of smaller axons at older ages. The use of OGSE with short diffusion times to sample the microstructural scale of restriction implies regional differences of axon diameters along the corpus callosum with preliminary results suggesting a dependence on age and sex.