Evidence of the diffusion time dependence of intravoxel incoherent motion in the brain

Purpose To investigate the diffusion time (TD) dependence of intravoxel incoherent motion (IVIM) signals in the brain. Methods A 3‐compartment IVIM model was proposed to characterize 2 types of microcirculatory flows in addition to tissue water in the brain: flows that cross multiple vascular segments (pseudo‐diffusive) and flows that stay in 1 segment (ballistic) within TD. The model was first evaluated using simulated flow signals. Experimentally, flow‐compensated (FC) pulsed‐gradient spin‐echo (PGSE) and oscillating‐gradient spin‐echo (OGSE) sequences were tested using a flow phantom and then used to examine IVIM signals in the mouse brain with TD ranging from ~2.5 ms to 40 ms on an 11.7T scanner. Results By fitting the model to simulated flow signals, we demonstrated the TD dependency of the estimated fraction of pseudo‐diffusive flow and the pseudo‐diffusion coefficient (D*), which were dictated by the characteristic timescale of microcirculatory flow (τ). Flow phantom experiments validated that the OGSE and FC‐PGSE sequences were not susceptible to the change in flow velocity. In vivo mouse brain data showed that both the estimated fraction of pseudo‐diffusive flow and D* increased significantly as TD increased. Conclusion We demonstrated that IVIM signals measured in the brain are TD ‐dependent, potentially because more microcirculatory flows approach the pseudo‐diffusive limit as TD increases with respect to τ. Measuring the TD dependency of IVIM signals may provide additional information on microvascular flows in the brain.