Passive cavitation detection-based feedback control for ultrasound-mediated blood-brain barrier opening in non-human primates

Despite the progress of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption, neuro-inflammatory responses and the high variability of the FUS transmission through the human skull make the control of the acoustic parameters challenging. In this study, we developed a high-field (7-T) magnetic resonance (MR)-guided FUS system with a feedback control based on passive cavitation detection (PCD) to explore BBB opening in non-human primates (NHP). The sonication parameters were: 2 min duration, 500-kHz frequency, pulse length of 10 ms, and pulse repetition frequency of 5 Hz. T1-weighted MR images acquired every 5 min revealed a maximum contrast enhancement of 67% ± 15% relative to muscle after 30 min of sonication. Safe sonications were achieved in the 3 sessions using real-time PCD-based feedback control of the acoustic pressure. The high resolution anatomical images and the high temporal/spatial resolution of contrast agent diffusion provide a unique tool for studying the mechanisms of BBB disruption and drug delivery in NHP. Furthermore, the PCD-based feedback control allows repeatable safe sonication regardless of the variation of skull attenuation, allowing comparisons across animals and experimental sessions.