title: Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.
abstract: Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chu
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, 333, Taiwan.|Department of Diagnostic Radiology and Intervention, Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan.
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Chai
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, 333, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Kang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
authors.affiliation: Department of Electrical Engineering, Chang-Gung University, Taoyuan, 333, Taiwan.|Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.|Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000503:physiopathology; D003287:Contrast Media / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D045423:Microbubbles / Q000627:therapeutic use; D051381:Rats; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003287:Contrast Media