Targeted Opening Of Blood-Brain Barrier Using MRI-Guided Focused Ultrasound Associated With Microbubbles

Objective: To study the dose-effect and time-effect of targeted and reversible opening blood-brain barrier(BBB) by the magnetic resonance(MR) image-guided focused ultrasound associated with microbubbles,and futher to explore the mechanisms of BBB disruption and the role of MRI in detecting the BBB opening in order to provide non-invasive ultrasound in thediseases of central nervous system with erperimental and theoretical evidence.Methods: (1)Craniotomies of Animals were performed before the experiments.(2)The focuses were targeted and opened BBB using the System of MRI-guided focused ultrasound associated with microbubbles.(3)Application the real time scan of CE-MRI monitor the permeability of BBB, and the rabbit brain was stained with H&E for histological examination which to determine the safety amplitudes of BBB disruption by focused ultrasound associated with.(4)Time-course of BBB permeability was detected by CE-MRI after irradiated by foucused ultraousnd. (5) The ultrastructural changes were observed with transmission electron microscope(TEM)Results: (1)MRI can accurately positioned and through the intensities of CE-MRI monitored the opening BBB by focused ultrasound.(2)Using a frequency of 1.1MHz and a power of 6W to the targeted location appeared the opening BBB when the exposure time was 8s;When exposure time was from 10s to 14s,the permibility of BBB in CE-MRI intensity achieve most level and compared with the groups of controls notably enhancement(p<0.05);but when exposure time were 16s and 20s ,the tintensities of CE-MRI occur to descent.(3)The histological findings indicated that brain tissue was not seen any changing when the exposure time was less than 10s.Ultrasound exposures using a time ranging from 12s to 14s were seen slight edema around the vessel and the endothelial cells in the location.Necrosis and erythrocyte extrvasation can been seen when the sonicate time was 16s and 20s.(4)The permibility of opening BBB reach the peak level when using the focused ultrasound associated with microbubbles to irradiate the targeted location after 2h-4h, and intensities of the CE-MRI occur peak amplitude; and was not demonstrable after 12h and 24h in CE-MRI.Conclusion: (1) MRI guided focused ultrasound can open the BBB safely and reversibaly with a frequency of 1.1MHz and a power of 6W in a certain dose of microbubbles at exposure time of 10s~14s.(2) BBB permeability peaked at 2~4h after focused ultrasound irradiation, and gradually declined at later observations period, normalized at 12 hours after irradiation.(3)T BBB permeability can be monitored by CE-MRI real-time.