controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring控制ultrasound-induced血脑屏障破坏使用被动声学排放监测.pdf

Controlled Ultrasound-Induced Blood-Brain Barrier Disruption Using Passive Acoustic Emissions Monitoring 1 2 1 1 Costas D. Arvanitis *, Margaret S. Livingstone , Natalia Vykhodtseva , Nathan McDannold 1 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America Abstract The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB) holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system’s performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective