Realistic Microstructure Simulator (RMS): Monte Carlo simulations of diffusion in three-dimensional cell...

Monte Carlo simulations of diffusion are commonly used as a model validation tool as they are especially suitable for generating the diffusion MRI signal in complicated tissue microgeometries.

Here we describe the details of implementing Monte Carlo simulations in three-dimensional (3d) voxelized segmentations of cells in microscopy images. Using the concept of the corner reflector, we largely reduce the computational load of simulating diffusion within and exchange between multiple cells. Precision is further achieved by GPU-based parallel computations.

Our simulation of diffusion in white matter axons segmented from a mouse brain demonstrates its value in validating biophysical models. Furthermore, we provide the theoretical background for implementing a discretized diffusion process, and consider the finite-step effects of the particle-membrane reflection and permeation events, needed for efficient simulation of interactions with irregular boundaries, spatially variable diffusion coefficient, and exchange.

To our knowledge, this is the first Monte Carlo pipeline for MR signal simulations in a substrate composed of numerous realistic cells, accounting for their permeable and irregularly-shaped membranes.

The proposed RMS pipeline makes it possible to achieve fast and accurate simulations of diffusion in realistic tissue microgeometry, as well as the interplay with other MR contrasts. Presently, RMS focuses on simulations of diffusion, exchange, and T₁ and T₂ NMR relaxation in static tissues, with a possibility to straightforwardly account for susceptibility-induced T₂^* effects and flow.