Effects of nongaussian diffusion on "isotropic diffusion measurements'': an ex-vivo microimaging and simulation study

TL;DR

This study investigates how non-Gaussian diffusion affects isotropic diffusion measurements in microimaging, revealing confounds in interpreting tissue microstructure due to anisotropic compartments and kurtosis effects.

Contribution

It provides analytical, simulation, and experimental insights into how non-Gaussian diffusion impacts isotropic diffusion MRI, challenging assumptions of Gaussian compartment models.

Findings

Diffusion anisotropy causes orientation-dependent diffusivity measurements.

Intracompartmental kurtosis introduces additional variance in isotropic diffusivity.

Simulations and experiments demonstrate these effects in fixed spinal cord tissue.

Abstract

Designing novel diffusion-weighted pulse sequences to probe tissue microstructure beyond the conventional Stejskal-Tanner family is currently of broad interest. One such technique, multidimensional diffusion MRI, has been recently proposed to afford model-free decomposition of diffusion signal kurtosis into terms originating from either ensemble variance of isotropic diffusivity or microscopic diffusion anisotropy. This ability rests on the assumption that diffusion can be described as a sum of multiple Gaussian compartments, but this is often not strictly fulfilled. The effects of nongaussian diffusion on single shot isotropic diffusion sequences were first considered in detail by de Swiet and Mitra in 1996. They showed theoretically that anisotropic compartments lead to anisotropic time dependence of the diffusion tensors, which causes the measured isotropic diffusivity to depend on gradient frame orientation. Here we show how such deviations from the multiple Gaussian compartments assumption conflates orientation dispersion with ensemble variance in isotropic diffusivity. Second, we consider additional contributions to the apparent variance in isotropic diffusivity arising due to intracompartmental kurtosis. These will likewise depend on gradient frame orientation. We illustrate the potential importance of these confounds with analytical expressions, numerical simulations in simple model geometries, and microimaging experiments in fixed spinal cord using isotropic diffusion encoding waveforms with 7.5 ms duration and 3000 mT/m maximum amplitude.