Sensitivities of statistical distribution model and diffusion kurtosis model in varying microstructural environments: A Monte Carlo study

The aim of this study was to investigate the microstructural sensitivity of the statistical distribution and diffusion kurtosis (DKI) models of non-monoexponential signal attenuation in the brain using diffusion-weighted MRI (DWI). We first developed a simulation of 2-D water diffusion inside simulated tissue consisting of semi-permeable cells and a variable cell size. We simulated a DWI acquisition of the signal in a volume using a pulsed gradient spin echo (PGSE) pulse sequence, and fitted the models to the simulated DWI signals using b-values up to 2500 s/mm². For comparison, we calculated the apparent diffusion coefficient (ADC) of the monoexponential model (b-value = 1000 s/mm²). In separate experiments, we varied the cell size (5-10-15 μm), cell volume fraction (0.50-0.65-0.80), and membrane permeability (0.001-0.01-0.1 mm/s) to study how the fitted parameters tracked simulated microstructural changes. The ADC was sensitive to all the simulated microstructural changes except the decrease in membrane permeability. The ADC increased with larger cell size, smaller cell volume fraction, and larger membrane permeability. The σ_stat of the statistical distribution model increased exclusively with a decrease in cell volume fraction. The K_app of the DKI model was exclusively increased with decreased cell size and decreased with increasing membrane permeability. These results suggest that the non-monoexponential models of water diffusion have different, specific microstructural sensitivity, and a combination of the models may give insights into the microstructural underpinning of tissue pathology.