Effect of ultrasound contrast agent dose on the duration of focused-ultrasound-induced blood-brain barrier disruption

It has been shown that focused ultrasound (FUS) is capable of noninvasive and reversible disruption of the blood-brain barrier (BBB) at target regions when applied in the presence of ultrasound contrast agent (UCA). The purpose of this study was to investigate the effects of UCA dose on the reversibility of BBB disruption induced by the same acoustical power of FUS. Sonications were applied at an ultrasound frequency of 1 MHz with a 5% duty cycle and a repetition frequency of 1 Hz. The brains of 66 male Sprague-Dawley rats were subjected to sonications with three doses of UCA. BBB integrity was evaluated via femoral vein injection of Evans Blue (EB) while the rats were anesthetized. The relationship between UCA dose and the region of EB extravasation was evaluated at an acoustic power of 1.43 W. The BBB disruption, as indexed by the amount of EB extravasation, was the largest immediately after the sonications. The quantity of Evans blue extravasation decreased as a function of time at various UCA doses. This study demonstrates that the appropriate dose of UCA not only enhance the BBB opening but also effectively aid in controlling the duration of BBB disruption.