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Double diffusion encoding is a magnetic resonance technique with applications in measuring microstructure. In many tissues, cell size (which is of a few micrometers) is an important biological parameter. Estimating an arbitrary pore size distribution from a diffusion attenuated signal usually relies on varying a single experimental setting. This inversion process is numerically unstable. Numerical simulations are presented, where multiple experimental settings are varied concomitantly. The inversion’s results show good agreement with ground truth.

The use of two independent diffusion periods between excitation and acquisition, known as double wave vector (DWV) diffusion-weighting or double diffusion encoding, was proven to yield structural information that it is otherwise not easily available in vivo. Comparing the signal difference between relative diffusion gradient orientations, the antiparallel-parallel and the parallel-perpendicular differences yield information on pore size and shape, respectively. However, results in vivo provided larger pore sizes than expected for axons in the corticospinal tract. This study exploits DWV sensitivity to pore shape and aims to obtain information on the extracellular contributions to the DWV pore size results presented here. The in vivo DWV experiments resulted in a positive parallel-perpendicular difference which is consistent with an irregularly shaped pore dominating the origin of the signal.