Revealing membrane integrity and cell size from diffusion kurtosis time-dependence

Motivation: The non-monotonic dependence of the diffusion kurtosis on diffusion time has been observed in tissue, yet its relation to membrane integrity and tissue geometry remains unknown. Goal(s): We investigate the relation between the characteristic time tpeak and the tissue parameters, such as cell size, volume fraction and permeability. Approach: We perform Monte Carlo simulations of diffusion and exchange in randomly, densely packed spheres with varying permeability, cell fractions and sizes, and identify the value of tpeak. Results: We obtain an empirical, albeit highly accurate relation of tpeak to tissue parameters in a broad parameter range. Impact: Diffusion-kurtosis time-dependence is sensitive to pathological changes in membrane integrity and cellular structure in diseases, such as ischemic stroke and tumors. Numerical simulations suggest an empirical interpretation of kurtosis time-dependence, offering a novel biomarker for in vivo evaluation of pathology.