Blood-Brain Barrier Opening by Individualized Closed-Loop Feedback Control of Focused Ultrasound

Objective and Impact Statement . To develop an approach for individualized closed-loop feedback control of microbubble cavitation to achieve safe effective focused ultrasound in combination with microbubble-induced blood-brain barrier opening (FUS-BBBO). Introduction FUS-BBBO is a promising strategy noninvasive localized brain drug delivery growing number clinical studies currently ongoing. Real-time monitoring are critical achieving FUS-BBBO. However, algorithms used the past were either open-loop or without consideration baseline level difference among subjects. Methods This study performed feedback-controlled by defining target based on stable individual subject “dummy” FUS sonication. The dummy sonication applied low acoustic pressure short duration presence microbubbles define that took into differences detected emissions. was then achieved through two phases: ramping-up phase reach maintaining at level. Results Evaluations wild-type mice demonstrated this trans-BBB model drug. efficiency increased as from 0.5 dB 2 causing vascular damage. Increasing 3 4 probability tissue Conclusions Safe using