title: 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.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Fan
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Huang
authors.forename: Yan-Jung
authors.initials: YJ
authors.lastname: Ma
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000528:radiation effects*; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000209:etiology*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging* / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000528:radiation effects; D004453:Echoencephalography / Q000379:methods; D057086:High-Intensity Focused Ultrasound Ablation / Q000009:adverse effects*; D008297:Male; D011829:Radiation Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome