TE dependent Diffusion Imaging (TEdDI) distinguishes between compartmental T 2 relaxation times

Abstract 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 (TE) in human white matter in vivo. We demonstrate that such TE dependence originates from compartment‐specific T2 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 T2 relaxation times, which is precluded by a limited signal‐to‐noise ratio when using multi‐echo relaxometry alone. HighlightsEmpirical evidence for different compartmental T2 values.TE dependency of diffusion MRI signals biases the interpretation of diffusion parameters.Including compartmental diffusivities in the biophysical models improves T2 relaxometry.Including compartmental T2's in the biophysical models improve diffusion modeling.Compartmental T2's may become valuable parameters for WM microstructure.