Abstract
Recently, focused ultrasound (FUS) has been proved to be able to open the blood-brain barrier (BBB) locally and temporarily, which can increase the performance of the treatment for brain diseases. However, rapid and acute symptoms like hemorrhage and ischemia stroke may occur if the applied acoustic pressure is too high. Currently, the reported imaging modalities for monitoring BBB opening are magnetic resonance imaging (MRI) and contrast enhanced ultrasound imaging (CEUI), but MRI is lack of temporal resolution and CEUI can not provide continuous monitoring due to the survival time of the microbubbles. Therefore, an imaging technique that can provide both dynamic and continuous monitoring of the transient response of the brain after FUS-induced BBB opening is desirable. In this study, we propose an intrinsic contrast based ultrasound time intensity curve (TIC) technique for real-time 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, the intensity of backscatter signal can be used be 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 to 85 % of the baseline at the end of the monitoring. 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 to 75 % of the baseline at the end of the monitoring; 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. In this study, the intrinsic contrast based ultrasound TIC was proved to be able to quantitatively reflect the variation of the cerebral blood flow, and the results were also verified by using photoacoustic imaging technique which is sensitive to blood content. The proposed method has potential to be applied to monitoring cerebral blood flow changes at different stages of treatment the degree of brain damage, improve parameters of focused ultrasound. The ultimate goal is to provide safer treatment parameters of focused ultrasound therapy in the future.