Opening of the blood-brain barrier by low-frequency (28-kHz) ultrasound: a novel pinhole-assisted mechanical scanning device.
Disruption of the blood-brain barrier (BBB) may be transiently achieved via high-frequency focused spherical ultrasound in the presence of microbubbles. In this experimental animal study, we sought to determine whether focal reversible opening of the BBB may be achieved using low-frequency (i.e., 20-30 kHz) planar ultrasonic waves. In the presence of microbubbles, we were able to obtain BBB opening using non-focused ultrasound irradiation with a frequency as low as 28 kHz. We also achieved a tight regulation of the ultrasound patterns by using a mechanical scanning device equipped with a pinhole. Histologic examination of the brains supported the feasibility of our system. The areas of BBB disruption obtained with this method were large enough to cover a typical circumscribed cerebral tumor mass. The inherent advantages of our BBB opening method include an improved portability, the possibility to obtain fairly wide areas of BBB opening and a low incidence of hemorrhagic complications. In addition, our system has the potential to reduce the need for image guidance for treating superficial brain lesions.
Liu
Hao-Li
HL
Department of Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan. haoliliu@mail.cgu.edu.tw
Pan
Chia-Hsin
CH
Ting
Cheng-Yu
CY
Hsiao
Ming-Jie
MJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging*; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D045423:Microbubbles; D051381:Rats; D012015:Reference Standards; D014464:Ultrasonic Therapy / Q000379:methods* / Q000592:standards; D014465:Ultrasonics; D014463:Ultrasonography
D003287:Contrast Media