Low-Pressure Burst-Mode Focused Ultrasound Wave Reconstruction and Mapping for Blood-Brain Barrier Opening: A Preclinical Examination.
Burst-mode focused ultrasound (FUS) exposure has been shown to induce transient blood-brain barrier (BBB) opening for potential CNS drug delivery. FUS-BBB opening requires imaging guidance during the intervention, yet current imaging technology only enables postoperative outcome confirmation. In this study, we propose an approach to visualize short-burst low-pressure focal beam distribution that allows to be applied in FUS-BBB opening intervention on small animals. A backscattered acoustic-wave reconstruction method based on synchronization among focused ultrasound emission, diagnostic ultrasound receiving and passively beamformed processing were developed. We observed that focal beam could be successfully visualized for in vitro FUS exposure with 0.5-2 MHz without involvement of microbubbles. The detectable level of FUS exposure was 0.467 MPa in pressure and 0.05 ms in burst length. The signal intensity (SI) of the reconstructions was linearly correlated with the FUS exposure level both in-vitro (r(2) = 0.9878) and in-vivo (r(2) = 0.9943), and SI level of the reconstructed focal beam also correlated with the success and level of BBB-opening. The proposed approach provides a feasible way to perform real-time and closed-loop control of FUS-based brain drug delivery.
Department of Electrical Engineering, Chang Gung University, Taoyuan, Taiwan.|Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Jingjing
J
Xia
Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.|Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
Po-Hsiang
PH
Tsui
Department of Electrical Engineering, Chang Gung University, Taoyuan, Taiwan.|Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Hao-Li
HL
Liu
D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000528:radiation effects*; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D051381:Rats; D014463:Ultrasonography / Q000379:methods*