Victor Menezes | Searcharxiv

arXiv2026

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

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.

physics.med-ph↗

arXiv2025

Quantitative acoustic monitoring of ensembles of weakly nonlinear microbubble oscillations in optically inaccessible environments

A growing class of ultrasound-mediated diagnostic and therapeutic technologies, including sonoporation and blood-brain barrier modulation, relies on microbubble contrast agents, where precise control of microbubble dynamics governs biological responses, efficiency, and safety. However, quantitative monitoring of microbubble oscillations in the stable, weakly nonlinear regime remains challenging, particularly in optically opaque and deep-tissue environments. Here, we introduce a linear acoustic wave propagation and superposition (LAWPS) framework that reconstructs microbubble radius-time dynamics directly from passively recorded acoustic emissions. By coupling Fourier-series representations of weakly nonlinear oscillations with linear monopole radiation theory, LAWPS extends classical monopole models to establish a reversible relationship between multi-frequency acoustic emissions and underlying radial bubble dynamics. Extending this framework to monodisperse microbubble ensembles, we derive optimal excitation and receive configurations and population-level correction factors that enable quantitative reconstruction of the ensemble-averaged microbubble dynamics. Using simultaneous optical and acoustic measurements, we demonstrate recovery of microbubble oscillations with ~5% relative error for oscillation amplitudes up to ~15% of equilibrium radius. Finally, we show that oscillations within the framework's operating regime (20% oscillation) generate sonoporation-relevant mechanical stress in vesicles as small as 10 micrometers (capillary number > 0.01), under physiologically relevant conditions. Together, this work establishes a quantitative framework for acoustic emission-based monitoring of weakly nonlinear microbubble oscillations in clinically relevant, optically inaccessible environments to enable improved control of emerging ultrasound diagnostic and therapeutic technologies.

physics.ins-det↗