Permeability assessment of the focused ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced...

Focused ultrasound (FUS) in conjunction with microbubbles has been shown to successfully open the blood-brain barrier (BBB) in the mouse brain. In this study, we compute the BBB permeability after opening in vivo. The spatial permeability of the BBB-opened region was assessed using dynamic contrast-enhanced MRI (DCE-MRI). The DCE-MR images were post-processed using the general kinetic model (GKM) and the reference region model (RRM). Permeability maps were generated and the K(trans) values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that K(trans) in the BBB-opened region (0.02 +/- 0.0123 for GKM and 0.03 +/- 0.0167 min(-1) for RRM) was at least two orders of magnitude higher when compared to the contra-lateral (control) side (0 and 8.5 x 10(-4) +/- 12 x 10(-4) min(-1), respectively). The permeability values obtained with the two models showed statistically significant agreement and excellent correlation (R(2) = 0.97). At histological examination, it was concluded that no macroscopic damage was induced. This study thus constitutes the first permeability assessment of FUS-induced BBB opening using DCE-MRI, supporting the fact that the aforementioned technique may constitute a safe, non-invasive and efficacious drug delivery method.