TE dependent Diffusion Imaging (TEdDI) distinguishes between compartmental T2 relaxation times

Biophysical modeling of macroscopic diffusion-weighted MRI signal in terms of microscopic cellular parameters holds the promise of quantifying the integrity of white matter. Unfortunately, even fairly simple multi-compartment models of proton diffusion in the white matter do not provide a unique, biophysically plausible solution. Here we report a nontrivial diffusion MRI signal dependence on echo time (T-E) in human white matter in vivo. We demonstrate that such T-E dependence originates from compartment-specific T-2 values and that it is a promising "orthogonal measure" able to break the degeneracy in parameter estimation, and to yield important relaxation metrics robustly. We thereby enable the precise estimation of the intra- and extra-axonal water T-2 relaxation times, which is precluded by a limited signal-to-noise ratio when using multi-echo relaxometry alone.