Restriction-induced time-varying transcytolemmal exchange rate: Revisiting diffusion MRI-based Kӓrger exchange model

Motivation: The diffusion MRI (dMRI) based two-compartmental Kӓrger exchange model is widely used to characterize transcytolemmal water exchange, but the influence of diffusion restriction remains unclear. Goal(s): To investigate how diffusion restriction and other acquisition and microstructural parameters impact the estimation of transcytolemmal water exchange rate constants in the Kӓrger model. Approach: Finite-difference-based numerical simulations were performed to quantitatively investigate time-varying transcytolemmal exchange rates of magnetization. Results: When the compartmental size is large, e.g. 15 μm (close to typical cancer cell sizes), Kӓrger-model-derived exchange rate constants will be significantly dependent on time, diffusion gradient waveforms and microstructural features, resulting in overestimation of water exchange. Impact: This work elucidates the influence of diffusion restriction on the estimation of transcytolemmal water exchange rate constants in the two-compartmental Kӓrger model, revealing that water exchange is overestimated in large compartmental sizes such as in tumors.