Whole brain diffusion-relaxation multidimensional MRI protocol with extended frequency range

Motivation: Diffusion-relaxation multidimensional MRI (MD-MRI) provides valuable sub-voxel diffusion frequency-dependent information. However, clinical scanner hardware limitations restrict the frequency range, decreasing sensitivity. Goal(s): Develop an MD-MRI protocol with a judicious experimental design, aimed at maximizing the frequency range while keeping the scan time under 30 minutes. Approach: We incorporated an oscillating gradient linear waveform to extend the diffusion frequency range at higher b-values, and applied simultaneous multi-slice (SMS) for full brain coverage within a 27-minute scan. Results: The expanded frequency range nearly doubled the diffusion frequency-dependent rate of change, with stronger dependencies observed in cortical gray matter compared to white matter. Impact: We introduce a diffusion-relaxation multidimensional MRI protocol that maximizes the diffusion frequency range within feasible scan times, enhancing sensitivity to diffusion frequency dependency, allowing the investigation of restricted diffusion, diffusion time dependency, and their relationship with brain microstructure in vivo.