Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood-brain-barrier disruption.
It has been shown that focused ultrasound (FUS) can disrupt the blood-brain barrier (BBB) noninvasively and reversibly at target locations when applied in the presence of ultrasound contrast agent (UCA). In this study, the dose-dependent effects of UCA on BBB disruption were investigated in the brains of 16 male Wistar rats sonicated by 1.0-MHz transcranial FUS, with the UCA present at four doses. The BBB disruption was evaluated quantitatively based on the extravasation of Evans blue (EB). The amount of EB extravasation in the brain increased with the quantity of UCA injected into the femoral vein prior to sonication. Moreover, the use of a suitable dose of UCA resulted in the BBB disruption being concentrated in the focal region instead of the entire brain. Our results indicate that injecting an appropriate quantity of UCA effectively increases and localizes the BBB disruption induced by transcranial FUS sonications.
Yang
Feng-Yi
FY
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan.
Fu
Wen-Mei
WM
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Wen-Shiang
WS
Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yeh
Wei-Lan
WL
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Win-Li
WL
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address: winli@ntu.edu.tw.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000033:anatomy & histology / Q000528:radiation effects; D001812:Blood-Brain Barrier / Q000528:radiation effects*; D003287:Contrast Media; D004307:Dose-Response Relationship, Radiation; D008297:Male; D011140:Polyurethanes; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D014465:Ultrasonics
D003287:Contrast Media; D011140:Polyurethanes