A diffusion model-free framework with echo time dependence for free-water elimination and brain tissue microstructure characterization

Purpose: The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill‐posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free‐water component. Theory and Methods: Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization. Results: Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free‐water contamination and to estimate tissue parameters. Conclusion: Formulation of the diffusion‐relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free‐water elimination.