The subharmonic resonance of lipid-encapsulated ultrasound contrast agents

Abstract

A salient feature of ultrasound contrast agent echo is their subharmonic response, a property that can be exploited for diagnostic contrast imaging. Here, we aim to explore the subharmonic behavior, specifically the subharmonic resonance, of two identical lipid-encapsulated microbubbles in close proximity to each other (center-to-center h = 6–16 μm) using finite element modeling. We simulated the subharmonic resonance response for bubbles (R0 = 0.5–1.5 μm) driven with 10 or 20 cycle tone bursts from 6 to 18 MHz under a peak negative pressure from 40to 180 kPa over a range of initial phospholipid packing values (σ0 = 0–0.01 N/m). Our results demonstrate that for increasing pressure, the transmit frequency at which the peak in subharmonic response is observed shifts monotonically towards higher frequencies (1–10%) for bubbles close to their buckling point, while the opposite trend occurs for bubbles with less dense initial packing (1–15%). For intermediate values of initial packing, a two-stage response is observed whereby the transmit frequency first decreases and then increases (5–9%) with increasing pressure. These results have implications in subharmonic-based diagnostic imaging techniques.