Subharmonic analysis using singular-value decomposition of ultrasound contrast agents.

Ultrasound contrast agents (UCAs) are designed to be used below 10 MHz, but interest is growing in studying the response of agents to high-frequency ultrasound. In this study, the subharmonic response of polymer-shelled UCAs with a mean diameter of 1.1 mum excited with 40-MHz tone-bursts of 1-20 cycles was analyzed. UCAs were diluted in water and streamed through a flow phantom that permitted single-bubble backscatter events to be acquired at peak-negative pressures from 0.75 to 5.0 MPa. At each exposure condition, 1000 single-bubble-backscatter events were digitized. Subharmonic content at 20 MHz was screened using a conventional and a singular-value-decomposition (SVD) method. The conventional method evaluated each event spectrum individually while the SVD method treated the 1000-event data set at one time. A subharmonic score (SHS) indicative of how much subharmonic content a 1000-event data set contained was computed for both methods. Empirical-simulation results indicated that SHSs obtained from the two methods were linearly related. Also, experimental data with both methods indicated that subharmonic likelihood increased with pulse duration and peaked near 2 MPa. The SVD method also yielded quantitative information about subharmonic events not available with the conventional method.