Quantitative assessment of in vivo focused ultrasound induced blood-brain barrier opening using magnetic resonance imaging

Delivery of therapeutic compounds to the brain is limited, because due to their molecular size they cannot cross the blood-brain barrier (BBB). Focused ultrasound (FUS) after administration of microbubbles into the blood-stream has been shown to open the BBB locally, non-invasively and reversibly. In this study, we investigated the time required for BBB´s permeability at the sonicated region to revert to its initial condition. BBB opening has also been shown to be induced safely for a variety of sonicating parameters. The group of parameters tested was as follows: Pulse Repetition Frequency 10 Hz, 20% duty cycle, pulse length 20 ms, two sets of 30 s sonication with a 30 s delay between, with peak-rarefactional pressure of 0.30 MPa. Contrast-enhanced high-resolution MRI (9.4 T) revealed BBB opening and allowed for the monitoring of the slow permeation of gadolinium in the hippocampus. BBB closing appeared to occur within a maximum of 5 days after sonication at the aforementioned parameters. The timeline of BBB closing will allow for time wise more efficient delivery of therapeutic compounds to the brain, as well as critical guidance for repeated drug administration over a period of time when necessary.