Ultrasonic contrast agent shell rupture detected by inertial cavitation and rebound signals

TLDR

Rupture pressure thresholds of ultrasound contrast agent microbubbles are critical for imaging, therapeutic development, and bioeffect evaluation. The study evaluates microbubble rupture by detecting acoustic emissions from single encapsulated microbubbles using a passive cavitation detector. Sinusoidal ultrasound pulses (0.9–4.6 MHz, 3–7 cycles, 0.07–5.39 MPa) were applied to Optison microbubbles in weak solutions at a 10 Hz repetition rate, and emissions were recorded with a 13‑MHz transducer. Broadband emissions detected 1–5 µs after excitation, consistent with inertial collapse and rebound, showed thresholds that increased with frequency (0.53, 0.87, 0.99 MPa) and decreased with pulse duration, offering a novel rupture detection method.

Abstract

Determining the rupture pressure threshold of ultrasound contrast agent microbubbles has significant applications for contrast imaging, development of therapeutic agents, and evaluation of potential bioeffects. Using a passive cavitation detector, this work evaluates rupture based on acoustic emissions from single, encapsulated, gas-filled microbubbles. Sinusoidal ultrasound pulses were transmitted into weak solutions of Optison/spl trade/ at different center frequencies (0.9, 2.8, and 4.6 MHz), pulse durations (three, five, and seven cycles of the center frequencies), and peak rarefactional pressures (0.07 to 5.39 MPa). Pulse repetition frequency was 10 Hz. Signals detected with a 13-MHz, center-frequency transducer revealed postexcitation acoustic emissions (between 1 and 5 /spl mu/s after excitation) with broadband spectral content. The observed acoustic emissions were consistent with the acoustic signature that would be anticipated from inertial collapse followed by "rebounds" when a microbubble ruptures and thus generates daughter/free bubbles that grow and collapse. The peak rarefactional pressure threshold for detection of these emissions increased with frequency (e.g., 0.53, 0.87, and 0.99 MPa for 0.9, 2.8, and 4.6 MHz, respectively; five-cycle pulse duration) and decreased with pulse duration. The emissions identified in this work were separated from the excitation in time and spectral content, and provide a novel determination of microbubble shell rupture.