Abstract

Abstract Diffusion-relaxation correlation multidimensional MRI (MD-MRI) replaces voxel-averaged diffusion tensor quantities and R1 and R2 relaxation rates with their multidimensional distributions, enabling the selective extraction and mapping of specific diffusion-relaxation spectral ranges that correspond to different cellular features. This approach has the potential of achieving high sensitivity and specificity in detecting subtle changes that would otherwise be averaged out. Here, the whole brain characterization of MD-MRI distributions and derived parameters is presented and the intrascanner test–retest reliability, repeatability, and reproducibility are evaluated to promote the further development of these quantities as neuroimaging biomarkers. We compared white matter tracts and cortical and subcortical gray matter regions, revealing notable variations in their diffusion-relaxation profiles, indicative of unique microscopic morphological characteristics. We found that the reliability and repeatability of MD-MRI-derived diffusion and relaxation mean parameters were comparable to values expected in conventional diffusion tensor imaging and relaxometry studies. Importantly, the estimated signal fractions of intra-voxel spectral components in the MD-MRI distribution, corresponding to white matter, gray matter, and cerebrospinal fluid, were found to be reproducible. This underscores the viability of employing a spectral analysis approach to MD-MRI data. Our results show that a clinically feasible MD-MRI protocol can reliably deliver information of the rich structural and chemical variety that exists within each imaging voxel, creating potential for new MRI biomarkers with enhanced sensitivity and specificity.