Model-Based Estimation of Microscopic Anisotropy in Macroscopically Isotropic Substrates Using Diffusion MRI

Non-invasive estimation of cell size and shape is a key challenge in diffusion MRI. Changes in cell size and shape discriminate functional areas in the brain and can highlight different degrees of malignancy in cancer tumours. Consequently various methods have emerged recently that aim to measure the microscopic anisotropy of porous media such as biological tissue and aim to reflect pore eccentricity, the simplest shape feature. However, current methods assume a substrate of identical pores, and are strongly influenced by non-trivial size distribution. This paper presents a model-based approach that provides estimates of pore size and shape from diffusion MRI data. The technique uses a geometric model of randomly oriented finite cylinders with gamma distributed radii. We use Monte Carlo simulation to generate synthetic data in substrates consisting of randomly oriented cuboids with various size distributions and eccentricities. We compare the sensitivity of single and double pulsed field gradient (sPFG and dPFG) sequences to the size distribution and eccentricity and further compare different protocols of dPFG sequences with parallel and/or perpendicular pairs of gradients. The key result demonstrates that this model-based approach can provide features of pore shape (specifically eccentricity) that are independent of the size distribution unlike previous attempts to characterise microscopic anisotropy. We show further that explicitly accounting for size distribution is necessary for accurate estimates of average size and eccentricity, and a model that assumes a single size fails to recover the ground truth values. We find the most accurate parameter estimates for dPFG sequences with mixed parallel and perpendicular gradients, nevertheless all other sequences, including sPFG, show sensitivity as well.