Detection of Intracerebral Hemorrhage and Transient Blood-Supply Shortage in Focused-Ultrasound-Induced Blood-Brain Barrier Disruption by Ultrasound Imaging

Focused ultrasound (FUS) in the presence of microbubbles can selectively open the blood-brain barrier (BBB). However, since overexcitation by FUS probably induces intracerebral hemorrhage, it is essential to develop an imaging approach for real-time detection of hemorrhage and blood-flow changes during FUS-induced BBB disruption. Here we investigated the feasibility of using ultrasound imaging to monitor the transient responses of FUS-induced BBB disruption. The BBB was disrupted with in-house-manufactured microbubbles in rats by 1-MHz FUS with a pressure of 1.1 MPa (pulse repetition frequency: 1 Hz, pulse duration: 10 ms, exposure time: 60 s) and imaged for the next 2 h. Ultrasound B-mode imaging was used to detect hyperechoic changes induced by hemorrhage and contrast-enhanced ultrasound (US) imaging was performed to analyze changes in blood flow. Hyperechoic spots appeared in B-mode images at 5 s after FUS sonication and contrast-enhanced US images simultaneously showed a region of transient blood-supply shortage in the sonicated area. Thus, the location of hyperechoic spots correlated with hemorrhagic patterns and the blood-supply-shortage region was consistent with the BBB-disrupted areas. Furthermore, we detected a transient hyperemic response in the unsonicated contralateral hemisphere brain. Our approach has potential as an immediate-feedback control tool for preventing the induction of intracerebral hemorrhage during FUS treatment.