Towards unconstrained compartment modeling in white matter using diffusion-relaxation MRI with tensor-valued diffusion encoding

Purpose To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T(2)values within a two-compartment model of white matter, and to explore the approach in vivo. Methods Sampling protocols featuring different b-values (b), b-tensor shapes (b(Delta)), and echo times (TE) were optimized using Cramer-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T(2)values were estimated in a model featuring two microstructural compartments represented by a stick and a zeppelin. Results Precise parameter estimates were enabled by sampling protocols featuring seven or more shells with uniqueb/b(Delta)/TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the stick compartment had a fraction of approximately 0.5 and, compared with the zeppelin compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 mu m(2)/ms) but higher T(2)values (85 vs. 65 ms). Children featured lower stick fractions (0.4). White matter lesions exhibited high zeppelin isotropic diffusivities (1.7 mu m(2)/ms) and T(2)values (150 ms). Conclusions Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.