A mechanistic investigation of subharmonic response from polymer-shelled microbubbles in response to high-frequency ultrasound

Abstract

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 excited below 10 MHz. This study investigated if polymer-shelled UCAs exhibited a similar behavior when excited at frequencies above 10 MHz. 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. 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 tone bursts. The four UCAs exhibited distinctly different compression-induced rupture thresholds that were linearly related to their STRR, but were uncorrelated with UCA size. The subharmonic response of the UCAs increased with increasing STRR. Thus, the UCAs with larger STRRs were more resilient to rupture, but they produced significantly greater subharmonic activity. 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.