A Novel Pinhole-Assisted Mechanical Scanning 28-kHz Ultrasonic Device to Open the Blood-Brain Barrier

摘要

Disruption of the blood-brain barrier (BBB) may be transiently achieved via high-frequency focused ultrasound in the presence of microbubbles. In the present study, we sought to confirm that BBB opening can be induced with low-frequency (20-30 kHz) unfocused ultrasonic waves. We developed a novel method using a pinhole-assisted mechanical-scanning configuration that allows the regulation of the exposure patterns. A tight regulation of the ultrasound patterns can be achieved using a mechanical scanning device equipped with a pinhole. Rat and pig experiments were conducted to show the feasibility of our technique. Histological examination of the sonicated brains was performed to analyze the minimum pressure threshold and the safety of the method, and contrast-enhanced MRI was also used to investigate the BBB-opening patterns. The inherent advantages of our BBB opening method include 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 brain drug delivery for superficial brain lesions.