Assessment of precision and accuracy of brain white matter microstructure using combined diffusion MRI and relaxometry

Abstract Joint modeling of diffusion and relaxation has seen growing interest due to its potential to provide complementary information about tissue microstructure. For brain white matter (WM), we designed an optimal diffusion‐relaxometry MRI protocol that samples multiple b ‐values, B‐tensor shapes, and echo times (TE). This variable‐TE protocol (27 min) has as subsets a fixed‐TE protocol (15 min) and a two‐shell dMRI protocol (7 min), both characterizing diffusion only. We assessed the sensitivity, specificity, and reproducibility of these protocols with synthetic experiments and in six healthy volunteers. Compared with the fixed‐TE protocol, the variable‐TE protocol enables estimation of the free water fraction while also capturing compartmental relaxation times. Jointly measuring diffusion and relaxation offers increased sensitivity and specificity to microstructure parameters in brain WM with voxelwise coefficients of variation below 10%.