Investigation of Single Frequency and Confocal Dual Frequency Focused Ultrasound with Contrast Agent on Local Blood-Brain Barrier Disruption

It has been shown that focused ultrasound (FUS) could disrupt local blood-brain barrier (BBB) noninvasively via the injection of ultrasound contrast agent (UCA). In this study, we use single frequency (518kHz) ultrasound and confocal dual frequency (513kHz+523kHz) ultrasound with the injection of UCA to disrupt the local BBB. Single frequency ultrasound and dual frequency ultrasound were set at almost the same acoustic negative peak pressure, and the pulse length was 10 ms. The brain of male Wistar rats were sonicated by ultrasound with the injection of UCA. The BBB disruption was evaluated by the extravasation of Evans Blue (EB). Additionally, we try out to find the optimal ultrasound parameters without producing hemorrhage, we use single frequency ultrasound with different doses of UCA. Expect this parameter could apply on future application.here was no difference at the total extravasation amount of EB between single and dual frequency ultrasound, but the EB distribution were slightly different. Because of the short duty cycle (1%), the enhancement of cavitation effect produced by dual frequency was not obvious. In addition, the BBBD area was related to the pressure distribution. The BBBD area produced by dual frequency ultrasound was larger than single frequency ultrasound. We optimize the ultrasound parameter to 20s sonication with 10μl/kg ultrasound contrast agent dose, in this case, we could open the BBB precisely on the focal region and cause nearly no hemorrhage. When the MR enhancement was quantitatively evaluated by the EB extravasation, the correlation was very high. When it went to T1-weighted SE, the correlation coefficient between them was 0.911 (p < 0.01). When it went to T1-weighted GE, the correlation coefficient between them was 0.981 (p < 0.01). In our result, we could use MR images to take the place of EB extravasation, and we could monitor the penetration of drugs or molecules in time.