A CMUT-Based Transcranial Focused Ultrasound Platform for Blood-Brain Barrier Opening in Small Animal Models

Abstract

Drug delivery to the brain is limited by the blood-brain barrier (BBB). We developed a capacitive micromachined ultrasonic transducer (CMUT)-based transcranial focused ultrasound system capable of both delivering therapy via BBB opening and monitoring microbubble activity across a broad frequency range. The performance of the geometrically focused half-ring array consisting of five transmitters and one receiving element was first assessed through simulations and in-vitro acoustic measurements with microbubbles. Use of phase-inversion (PI) during transmission effectively suppressed CMUT-generated harmonics and enhanced broadband detection of microbubble emissions. In rats, the same system achieved spatially localized BBB opening, confirmed by T1-weighted magnetic resonance imaging. BBB permeability mapping using dynamic contrast-enhanced magnetic resonance imaging (Ktrans) scaled with pressure. Time-resolved acoustic spectra captured microbubble arrival and decay kinetics, and 7-20dB enhancement in the effective dynamic range is observed with PI processing of acoustic emission signals. Together, these findings establish an integrated CMUT platform for combined therapeutic and sensing applications for BBB opening in small animal models, providing a foundation for future real-time, frequency-agile, closed-loop control of ultrasound-mediated drug delivery to the brain.