CMUT-Based Focused Ultrasound Transmit Array for Blood-Brain Barrier Opening in Small Animal Models

Transcranial focused ultrasound (tFUS) combined with microbubbles (MBs) has emerged as a promising strategy for transiently opening the blood-brain barrier (BBB), enhancing drug delivery to the brain. Existing FUS systems for BBB opening primarily rely on piezoelectric transducers for both transmission and reception. While capacitive micromachined ultrasonic transducers (CMUTs) have been proposed as passive cavitation detectors (PCD) due to their wide bandwidth, their potential as transmitters in tFUS remains largely unexplored, mainly due to their inherent nonlinearity and limited pressure output. In this study, we designed a small 6-element CMUT-based transmit array system and employed polyphase modulation to isolate MB-generated nonlinear harmonics, a critical factor for feedback control during BBB opening. The results showed good agreement between simulated and experimental pressure field distributions. Additionally, the system demonstrated effective suppression of CMUT-generated harmonics and successful extraction of MB-generated nonlinear harmonics, confirming the feasibility of this approach for BBB opening in small animal models.