Quantitative evaluation of focused ultrasound with a contrast agent on blood-brain barrier disruption.
The use of an ultrasound contrast agent (UCA) with focused ultrasound sonication has the potential to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at target locations. This study investigated the effects of UCA dose and ultrasound pressure on BBB disruption. Sonications were applied at 1 MHz with a burst length of 10 ms, a 1% duty cycle and a repetition frequency of 1 Hz. The duration of the sonication was 30 s. In in vivo experiments, 16 male Wistar rats were sonicated in the presence of UCA at four doses (0, 30, 60 and 90 microL/kg). BBB integrity was evaluated by injecting Evans blue (EB) into the femoral vein of anesthetized rats. The relationship between UCA dose and the region of EB extravasation was evaluated at ultrasound pressures of 0.9 and 1.2 MPa. The BBB disruption, as quantified by the amount of EB extravasation, was significantly greater in rats injected with UCA at a dose of 60 or 90 microL/kg than at a dose of 0 or 30 microL/kg. The amount of EB extravasation increased monotonically with the quantity of UCA injected into the femoral vein before sonication. Furthermore, the BBB disruption could be enhanced in the focal region relative to the surrounding region with a higher dose of UCA (60 or 90 microL/kg). This study demonstrates that BBB disruption can be both increased and localized to the focal region by injecting an appropriate quantity of UCA before performing focused ultrasound sonications.
Yang
Feng-Yi
FY
Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei, Taiwan.
Fu
Wen-Mei
WM
Yang
Rong-Sen
RS
Liou
Houng-Chi
HC
Kang
Kai-Hsiang
KH
Lin
Win-Li
WL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications; D005268:Femoral Vein; D008297:Male; D045423:Microbubbles; D051381:Rats; D017208:Rats, Wistar; D013010:Sonication