Impact of Activation Threshold Selection and Data Averaging to Improve Pressure Estimation using Ultrasound Imaging and Phase-Change Contrast Agents

Abstract

A phase-change contrast agent (PCCA) is a liquid nanodroplet (ND) that can phase transition into a gaseous microbubble (MB) when exposed to pulsed ultrasound (US) of sufficient peak negative pressure. Previously, our group has shown that PCCA activation is linearly related to the hydrostatic pressure of the surrounding media. As increases in the hydrostatic pressure requires higher US energies to phase transition, we hypothesize this relationship can be used to allow noninvasive pressure estimation in remote vascular structures. After applying various levels of hydrostatic pressures, the goal of this research project was to establish a more robust quantitative US method to determine the activation threshold of PCCAs in a flow phantom model. Decafluorobutane (DFB) NDs were formulated in house using the popular condensation method. Activation and detection of the resultant MBs was captured using a programmable US system (Vantage 256, Verasonics Inc). A custom scan sequence was applied with interleaved pulsed US transmissions for both PCCA activation and MB detection. Using a progressive increase in peak negative pressures from 3 to 6 MPa, a series of US images were collected at each discrete interval (N = 200). Preliminary results at room temperature revealed that as hydrostatic pressure increased there was a corresponding increase in PCCA activation threshold (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> > 0.88, p < 0.001). Overall, this study introduces a more consistent method to determine PCCA activation thresholds and use of sample averaging to help minimize measurement variance during threshold quantification.