Acoustic Emission-Feedback Planar Ultrasound System for Localized Blood-Brain Barrier Opening Monitoring

Transcranial pulsed ultrasound with microbubbles has been shown to temporally open the blood-brain barrier (BBB) to allow therapeutic agents to penetrate into the CNS for improved therapeutic efficacy. Recent studies have shown the feasibility of using passive cavitation detection (PCD) for monitoring or real-time control of the BBB opening in a focused ultrasound device. Planar ultrasound has unique advantages including the capability to create larger BBB openings in a single exposure, simple operation, and reduced reliance on medical imaging for sonication guidance. This study proposes a novel planar ultrasound apparatus design that can provide real-time analysis for ultrasound BBB opening monitoring. In-vitro tube phantom experiments were conducted to characterize the dependence of the energy spectrum density (ESD) change with microbubble infusion. In-vivo experiments characterized the dependence of ESD change on BBB opening. We showed that the proposed configuration provide superior ESD detection than traditional water-immersed PCD arrangement and can well correlated with the cavitation activity either in the in vitro or in vivo measurement. The ESD response corresponds well to the occurrence of BBB-opening. In animal groups which demonstrated successful BBB-opening, the peak ESD was significantly higher (12.22 +/- 7.019and 14.763 +/- 11.812dB in 0.332 and 0.463-MPa exposure). The 5-dB ESD level was found to be a valid threshold level to discriminate between the BBB-intact and BBB-opened groups to provide both high detection sensitivity (100%) and specificity (88%). These results may facilitate the design of a planar ultrasound treatment apparatus for BBB opening and drug delivery to the brain.