A Quantitative Pressure and Microbubble-Size Dependence Study of Focused Ultrasound-Induced Blood-Brain Barrier Opening Reversibility in vivo Using MRI

摘要

Focused Ultrasound (FUS) in conjunction with the systemic administration of microbubbles has been shown to open the blood-brain barrier (BBB) selectively, non-invasively and reversibly. In this study, we investigate the dependence of the BBB opening’s reversibility on the peak-rarefactional pressure (PRP) (0.30 MPa - 0.60 MPa) as well as the microbubble size (diameters of 1-2, 4-5 or 6-8 microns) in mice using contrast-enhanced T1-weighted (CE-T1) MR images (9.4 T). Volumetric measurements of the diffusion of Gd-DTPA-BMA into the brain parenchyma were used for the quantification of the BBB-opened region on the day of sonication and up to five days thereafter. The volume of opening was found to increase with both pressure and microbubble diameter. The duration required for closing was found to be proportional to the volume of opening on the day of opening, and ranged from 24 hours, for the smaller microbubbles, to 5 days for high PRPs. Overall, larger bubbles did not show significant differences. Also, the extent of BBB opening decreased radially towards the focal region until BBB’s integrity was restored. In the cases where histological damage was detected, it was found to be highly correlated with hyperintensity in the pre-contrast T1 images.