Nonparametric D-R₁-R₂ distribution MRI of the living human brain

Diffusion-relaxation correlation NMR can simultaneously characterize both the microstructure and the local chemical composition of complex samples that contain multiple populations of water. Recent developments on tensor-valued diffusion encoding and Monte Carlo inversion algorithms have made it possible to transfer diffusion-relaxation correlation NMR from small-bore scanners to clinical MRI systems. Initial studies on clinical MRI systems employed 5D D-R₁ and D-R₂ correlation to characterize healthy brain in vivo. However, these methods are subject to an inherent bias that originates from not including R₂ or R₁ in the analysis, respectively. This drawback can be remedied by extending the concept to 6D D-R₁-R₂ correlation. In this work, we present a sparse acquisition protocol that records all data necessary for in vivo 6D D-R₁-R₂ correlation MRI across 633 individual measurements within 25 min-a time frame comparable to previous lower-dimensional acquisition protocols. The data were processed with a Monte Carlo inversion algorithm to obtain nonparametric 6D D-R₁-R₂ distributions. We validated the reproducibility of the method in repeated measurements of healthy volunteers. For a post-therapy glioblastoma case featuring cysts, edema, and partially necrotic remains of tumor, we present representative single-voxel 6D distributions, parameter maps, and artificial contrasts over a wide range of diffusion-, R₁-, and R₂-weightings based on the rich information contained in the D-R₁-R₂ distributions.