Evaluation of the diffusion time dependence of the IVIM effect based on realistic capillary flow simulations

The intra-voxel incoherent motion (IVIM) effect is an additional signal attenuation in in-vivo diffusion-weighted MRI due to blood microcirculation. The dependence of this effect on diffusion time is of high interest because it may inform about the architecture of blood vessels in perfusion studies and help optimizing diffusion scans to avoid the IVIM bias. This dependence is derived here using capillary blood trajectories obtained by realistic flow simulations in capillary bed samples of mouse brain cortex derived from two-photon microscopy. Using the gaussian phase approximation, NMR signal attenuation due to IVIM is derived for pulsed-gradient diffusion sequences at different diffusion times and for sequences with flow-compensated gradient shapes by calculating the product of the gradient moment spectra with the spectral density of the simulated blood velocity autocorrelation function. The results suggest that the microcirculation underlying the IVIM effect cannot be faithfully depicted by the commonly used models of diffusive or ballistic flow, but rather as a correlated random motion with a correlation time in the range of 60–120 milliseconds. Consequently, the correlation time appears to be an interesting, MRI-accessible endpoint to characterize microcirculation. Further, the flow compensation as a means of suppressing the IVIM effect in diffusion measurements may not be fully effective.