Use of multi-flip angle measurements to account for transmit inhomogeneity and non-Gaussian diffusion in DW-SSFP

Diffusion-weighted steady-state free precession (DW-SSFP) is an SNR-efficient diffusion imaging method. The improved SNR and resolution available at ultra-high field has motivated its use at 7T. However, these data tend to have severe B₁ inhomogeneity, leading not only to spatially varying SNR, but also to spatially varying diffusivity estimates, confounding comparisons both between and within datasets. This study proposes the acquisition of DW-SSFP data at two-flip angles in combination with explicit modelling of non-Gaussian diffusion to address B₁ inhomogeneity at 7T. Data were acquired from five fixed whole human post-mortem brains with a pair of flip angles that jointly optimize the diffusion contrast-to-noise (CNR) across the brain. We compared one- and two-flip angle DW-SSFP data using a tensor model that incorporates the full DW-SSFP Buxton signal, in addition to tractography performed over the cingulum bundle and pre-frontal cortex using a ball & sticks model. The two-flip angle DW-SSFP data produced angular uncertainty and tractography estimates close to the CNR optimal regions in the single-flip angle datasets. The two-flip angle tensor estimates were subsequently fitted using a modified DW-SSFP signal model that incorporates a gamma distribution of diffusivities. This allowed us to generate tensor maps at a single effective b-value yielding more consistent SNR across tissue, in addition to eliminating the B₁ dependence on diffusion coefficients and orientation maps. Our proposed approach will allow the use of DW-SSFP at 7T to derive diffusivity estimates that have greater interpretability, both within a single dataset and between experiments.