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

Abstract

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.