Repeated hippocampal blood-brain barrier opening controlled via three-dimensional transcranial acoustic imaging: Safety study in a porcine model

摘要

Transient blood-brain barrier (BBB) opening via focused ultrasound (FUS) combined with intravenously circulating microbubbles (MBs) may have a role in the treatment of Alzheimer's disease (AD). Spectral characteristics of MB emissions recorded during the procedures using single-element detectors have correlated with biological outcomes [McDannold et al. PMB 2006], leading to the development of acoustic emissions-based controllers that aim to achieve safe and consistent BBB opening [O'Reilly et al. Radiology 2012]. We recently demonstrated that 3D mapping of subharmonic MB activity can be used to calibrate FUS exposure levels for BBB opening [Jones et al. IEEE IUS 2016]. Here we evaluate the safety of this imaging-based calibration approach during repeated volumetric sonications targeted to the hippocampus in a large animal model.