Susceptibility-induced internal gradients reveal axon morphology and cause anisotropic effects in the dMRI signal

Diffusion-weighted MRI is our most promising method for estimating microscopic tissue morphology in vivo. The signal acquisition is based on scanner-generated ex ternal magnetic gradients. However, it will also be affected by susceptibility-induced in ternal magnetic gradients caused by interaction between the tissue and the static magnetic field of the scanner. With 3D in silico experiments, we show how internal gradients cause morphology-, compartment-, and orientation-dependence of spin-echo and pulsed-gradient spin-echo experiments in myelinated axons. These effects are unseen in previous 2D modelling. For an ex vivo monkey brain, we observe the orientation-dependency generated only when including non-circular cross-sections in the in silico morphological configurations, and find orientation-dependent deviation of up to 17% for diffusion tensor metrics. Our findings underline the importance of accounting for realistic 3D axon morphology in modelling. Interestingly, the morphology-specific orientation-dependency trends show potential for a novel sensitivity to morphology, which is not attainable by the theoretical diffusion-weighted MRI signal itself.