In-vivo quantitative permeability assessment of the focused-ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced MRI

Pharmacokinetic modeling with dynamic contrast-enhanced MRI (DCE-MRI) has been established as an in vivo technique that estimates the permeability of the vessels. In this study, the most reliable model for permeability assessment of the focused ultrasound (FUS)-induced BBB opening was determined using DCE-MRI. Six mice were sonicated on the right hippocampal region using FUS at the peak-rarefactional acoustic pressure of 0.30 MPa, after intravenous injection of lipid-shelled microbubbles (4-5 μm in diameter). The general kinetic model (GKM) and the reference region model (RRM) were applied on the dynamic MR images to estimate the K_trans values. The GKM-derived K_trans for a specific volume of interest was found to be 0.02 ± 0.0123 min^-1, while RRM yielded statistically insignificantly higher values, 0.03 ± 0.0167 min^-1. Both GKM and RRM exhibited significantly low K_trans values in the control region (0 and 8.5 ± 12×10^-4 min^-1 respectively). The two models showed excellent correlation (R²=0.97), verifying the consistency of the permeability measurements. However, the poor time-concentration curves of RRM suggest that GKM is more suitable for permeability estimation. In conclusion, GKM was found to be the optimal model for the permeability assessment of the FUS-induced BBB opening and the associated drug delivery efficacy.