ABSTRACT Diffusion MRI techniques are widely used to study in vivo changes in the human brain connectome. However, to resolve and characterise white matter fibres in heterogeneous diffusion MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and restrictive constraints. We have recently introduced a 5D relaxation-diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo-times in order to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation-diffusion distributions where contributions from different sub-voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre-specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins in order to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation-specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along distinct fibre bundles. If combined with fibre-tracking algorithms, the methodology presented in this work may be useful for investigating the microstructural properties along individual white matter pathways.

Visualizing orientation-specific relaxation-diffusion features mapped onto orientation distribution functions estimated via nonparametric Monte Carlo MRI signal inversion