Temporal evolution of subharmonic emissions from a lipid-encapsulated contrast agent

Abstract

A large body of work has investigated the influence of the excitation pulse, agent size distribution, and the ambient pressure on the subharmonic response of microbubble contrast agents (MCA). The purpose of this study was to investigate the temporal evolution of the subharmonic emissions, i.e., whether the subharmonic response is influenced by the time elapsed since agent constitution. We measured subharmonic emissions from a commercial lipid-encapsulated contrast agent (Targestar-P®, Targeson Inc., San Diego) over the time span of 60 min. The excitation parameters were as follows: 10-MHz frequency, 30–290 kPa pressures, 60 cycles, and 1-kHz pulse repetition frequency. The subharmonic emissions were observed to increase by 11 dB over 60 min relative to those measured immediately after reconstitution. The most striking increase (>8 dB) was observed in the first 15 min. Although we did not observe a change in the agent size distribution, the pressure threshold for subharmonic emissions reduced by nearly two-fold within the time span of our measurements. This work demonstrates that time evolution of subharmonic emissions could bias quantitative estimates obtained from techniques such as subharmonic imaging and subharmonic-aided pressure estimation. Additionally, these findings suggest the possibility for improving subharmonic emission by careful agent design.