In vivo rat-brain mapping of multiple gray matter water populations using nonparametric D(omega)-R1-R2 distributions MRI

Massively Multidimensional Diffusion MRI combines tensor-valued encoding, oscillating gradients, and diffusion-relaxation correlation to provide multicomponent sub-voxel parameters depicting the tissue microstructure. This method was successfully implemented ex vivo in micro-imaging systems and in clinical conditions but with a reduced diffusion frequency ({omega}) range due to the use of classical tensor-valued encoding. We demonstrate here its preclinical in vivo implementation with a protocol of 389 contrast images probing a wide diffusion frequency range of 18 to 92 Hz at b-values up to 2.1 ms/{micro}m2 enabled by the use of modulated gradient waveforms and combined with multislice high-resolution and low-distortion EPI acquisition with segmented and full reversed phase-encode acquisition. This framework allows the identification of diffusion{omega} -dependence in the rat cerebellum and olfactory bulb gray matter (GM) and the parameter distributions are shown to resolve two water pools in GM with different diffusion coefficients, shapes,{omega} -dependence, relaxation rates, and spatial repartition whose attribution to specific microstructure could modify the current understanding of the origin of restriction in GM.