Impact of phase-change contrast agent size during activation using ultrasound

Abstract

Phase-change contrast agents (PCCAs) are liquid nanodroplets (ND) that transition into gas microbubbles (MB) when exposed to pulsed ultrasound (US) . The purpose of this study was to investigate the activation threshold of size-isolated PCCAs under physiologically relevant hydrostatic pressures. Size-isolated PFB NDs were prepared using an extrusion method and filter sizes of 100 or 400 nm. Using a programmable US scanner and linear array transducer, a custom scan sequence was implemented that interleaved pulsed US transmissions for both PCCA activation and MB detection. An automated US pressure sweep was performed (3 to 6 MPa, N = 200 discrete intervals), and grayscale US images were acquired at each increment. PCCAs were circulated through a flow phantom at 37 deg. Hydrostatic pressures applied to the PCCAs was controlled by constriction of flow phantom tubing. Reference measures were recorded by a calibrated pressure catheter. Activation thresholds were quantified using custom MATLAB software. The US-detected PCCA activation threshold increased with increased hydrostatic pressure in the range of 0 to 75 mmHg. The 100 nm size-isolated PCCAs activated at a higher US pressure as compared to 400 nm agents (4.3 ± 0.2 mmHg versus 3.7 ± 0.2 mmHg, p < 0.001). A positive correlation was found between the PCCA activation threshold and applied hydrostatic pressure for both 100 and 400 nm PCCAs (R 2 > 0.95, p < 0.001). This strong linear relationship could be exploited for noninvasive pressure estimation using US and PCCAs.