Influence of shell parameters on response of polymer-shelled microbubbles to high-frequency ultrasound

Polymer-shelled ultrasound contrast agents (UCAs) can undergo a "compression only" behavior leading to shell rupture and nonlinear response of the released gas bubbles when ultrasonically excited below 10 MHz. This study investigated if polymer-shelled UCAs exhibited a similar behavior when excited at frequencies above 10 MHz. Accordingly, two experiments were performed: one examined the compression-induced rupture of UCA shells by subjecting them to static overpressure, and the other investigated subharmonic components in the backscattered signal produced by individual UCAs sonicated with 20-MHz tonebursts. Four varieties of polylactide-shelled UCAs, each with a distinct shell-thickness-to-radius ratio (STRR), were employed; the STRRs were 7.5, 40, 65, and 100 nm/μm. Different UCA types exhibited distinctly different rupture thresholds that were linearly related to their STRR, but uncorrelated with UCA size. The subharmonic response of these polymer-shelled UCAs did not exhibit a strong correlation with UCA-rupture pressures and, consequently, their STRRs. Although the Philips UCAs had greater STRRs in comparison to Point UCAs and were more resilient, they produced significantly greater subharmonic activity than the Point UCAs. The results of this two-part study indicated that the polymer-shelled UCAs may not adhere to the rupture-based mechanism of subharmonic generation when excited at 20 MHz.