Intrinsic contrast based ultrasound time intensity curve analysis for monitoring focused-ultrasound induced blood-brain-barrier disruption

In this study, we propose an intrinsic contrast based ultrasound time intensity curve (TIC) technique for monitoring the dynamic response of FUS-induced BBB opening on a rat model. Because the ultrasound backscattering coefficient of the cerebral blood is higher than that of the peripheral brain tissues at the used imaging frequency, the intensity of backscatter signal can be used as the indicator to analyze the variation of the cerebral blood flow and hemorrhage during FUS-induced BBB opening. Two considerable cases of BBB opening - with and without hemorrhage - was performed by 1-MHz FUS and monitored by the proposed TIC technique. In the case with microhemorrhage, the TIC of the sonicated area (left brain) rose immediately after the BBB opening and then gradually declined after 10 minutes. The TIC of controlled contralateral (right) brain gradually dropped. The response of the left brain was dominated by the brain hemorrhage and was suspiciously mingled with the effect of ischemia. The TIC of the right brain showed a high performance of flow auto-regulation which is the forced vasoconstriction of the right brain compensating blood to the left brain. In the case without hemorrhage, the TIC of the left brain gradually dropped; the right one was in accordance with the result of the condition with microhemorrhage. In this case, FUS induced vasoconstriction and thus caused reduction of blood volume in the left brain, and this lead to the compensation of the blood from the right brain induced by flow auto-regulation. Overall, the proposed intrinsic contrast based ultrasound TIC technique was proved to be able to quantitatively reflect the variation of the cerebral blood volume.