A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents

TLDR

Contrast bubble destruction, governed by shell material and gas composition, is critical for emerging diagnostic and therapeutic ultrasound applications. The study measured ultrasonic fragmentation thresholds and inertial cavitation doses of Optison, Sonazoid, and biSpheres under varied acoustic conditions, comparing broadband noise emissions as a proxy for IC. Optison and Sonazoid exhibited low fragmentation thresholds (≈0.13–0.58 MPa) while polymer‑shelled biSpheres had higher thresholds (≈0.19–0.96 MPa); Sonazoid produced the greatest IC dose, whereas thick‑shelled biSpheres had the highest threshold and lowest IC dose, requiring more cycles to reach steady state.

Abstract

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC “dose”). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean=0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean=0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.