In-vivo investigation of the effects of ultrasound contrast agent and focused ultrasound on blood-brain barrier disruption

In this study, the effects of UCA injection and ultrasound pressure on BBB disruption were investigated. Sonications were applied with an ultrasound frequency of 1 MHz, a burst length of 10ms at 1% duty cycle, and a repetition frequency of 1 Hz. The duration of the whole sonication was 30s. In-vivo experiments, twelve male Wistar rats were sonicated with four different UCA injections (0, 30, 60, 90 μL/kg). BBB integrity was evaluated via femoral vein injection of Evans Blue (EB) while rats were anesthetized. The relationship between the UCA injection and the region of EB flux was evaluated under 1.9 and 2.5 MPa ultrasound pressure. The BBB disruption, as indexed by EB flux, was significantly greater in rats injected with 60 or 90μL/kg UCA as compared to 0 or 30μL/kg injection. The amount of EB flux systematically increased as a function of the injection of UCA injected into the femoral vein before sonication. Furthermore, the BBB disruption could be concentrated in the focal region relative to the neighboring tissue with a higher injection of UCA (60 or 90μL/kg). This study demonstrates that an appropriate injection of UCA could effectively increase and localize the BBB disruption in the focal region for ultrasound sonication.