In vitro comparison of subharmonic-aided pressure estimation sensitivity among microfluidic monodisperse microbubbles, sonazoid, and definity

Abstract

The subharmonic response of microbubble-based ultrasound contrast agents (UCAs) typically exhibits an inverse linear relationship with the surrounding ambient pressure. Although SHAPE has been clinically successful, the sensitivity of SHAPE at lower pressures is suboptimal. While previous studies optimized SHAPE using commercially available UCAs without considering their size distribution, in this study, two SHAPE-specific monodisperse microbubble (MMB) UCAs with different bubble diameters were compared with commercial polydisperse UCAs as well as their buoyancy-separated subpopulations. UCAs were imaged in a hydrostatic tank containing 350 ml of deionized water. The pressure within the tank was increased from 0–100 mmHg. Using a modified Logiq E10 scanner (GE HealthCare) with acoustic power optimization, SHAPE data was acquired using subharmonic imaging mode with a C1-6 curvilinear probe at 2.5 MHz (receiving at 1.25 MHz). After identification of the optimal acoustic output power, MMB with a mean diameter 1.66 mm demonstrated a mean SHAPE sensitivity of −0.207 dB/mmHg (r2 = 0.94). The second MMB with a mean diameter 3.45 mm demonstrated a mean SHAPE sensitivity of −0.300 dB/mmHg (r2 = 0.92). In contrast, this was 2.5–4 times more sensitive than the two polydisperse UCAs (slope range of −0.081 to −0.074 dB/mmHg) and 1.45–5 times more sensitive than the buoyancy-separated UCAs (ranging −0.061 to −0.142 dB/mmHg). These results suggest that SHAPE-optimized MMB are more sensitive to measuring changes in pressure.