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

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 Ktrans values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that Ktrans 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 × 10−4 ± 12 × 10−4 min−1, respectively). The permeability values obtained with the two models showed statistically significant agreement and excellent correlation (R2 = 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.