Characterisation of white matter asymmetries in the healthy human brain using diffusion MRI fixel-based analysis

The diffusion tensor model for diffusion MRI has been used extensively to study asymmetry in the human brain white matter. However, given the limitations of the tensor model, the nature of any underlying asymmetries remains uncertain, particularly in crossing fibre regions. Here, we provide a more robust characterisation of human brain white matter asymmetries based on fibre-specific diffusion MRI metrics and a whole-brain data-driven approach. We used high-quality diffusion MRI data (n = 100) from the Human Connectome Project, the spherical deconvolution model for fibre orientation distribution estimation, and the Fixel-Based Analysis framework to utilise crossing fibre information in registration, data smoothing and statistical inference. We found many significant asymmetries, widespread throughout the brain white matter, with both left>right and right>left dominances observed in different pathways. No influences of sex, age, or handedness on asymmetry were found. We also report on the relative contributions of microstructural and morphological white matter properties toward the asymmetry findings. Our findings should provide important information to future studies focussing on how these asymmetries are affected by disease, development/ageing, or how they correlate to functional/cognitive measures.