Singular-value-decomposition investigation of the sub-harmonic response of 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 (HFU). In this study, we analyzed the sub-harmonic response of polymer-shelled UCAs with a mean diameter of 1.1 mum excited with 40-MHz tone bursts of 1 to 20 cycles. UCAs were diluted in water and streamed through a flow phantom that permitted single-bubble 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. Sub-harmonic content at 20 MHz was screened using a conventional method and a singular-value-decomposition (SVD) method. The conventional method evaluated each event spectrum individually while the SVD method treated the 1000-event dataset at one time. A sub-harmonic score (SHS) indicative of how much sub-harmonic content a 1000-event dataset 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 sub-harmonic likelihood increased with pulse duration and peaked near 2 MPa. The SVD method also yielded quantitative information about UCA physics not available with the conventional method.