Observed cumulative time delay between second harmonic and fundamental component of pressure wave fields propagating through ultrasound contrast agents

Several studies on the propagation velocity of pressure wave fields through ultrasound contrast agents (UCAs) have been reported in the literature. However, the variation of propagation velocity between the fundamental and the second harmonic component generated during the propagation of ultrasound through UCAs has, to our knowledge, not been studied yet. To this scope, dedicated transmission and backscattering measurements of pressure wave fields propagating through SonoVue and Definity contrast agents, are analyzed. Results show the occurrence of a cumulative delay between the time signals related to the second harmonic and fundamental component, suggesting a smaller propagation velocity for the second harmonic as compared to the fundamental component. Moreover, this time delay increases with increasing UCA concentration and propagation path length of ultrasound trough microbubbles, depends on mechanical index and frequency, and, most importantly, is not observed in the absence of UCAs. These results may be relevant to contrast-enhanced ultrasonography, opening up to new possibilities to increase contrast-to-tissue ratios and to quantify UCA concentrations.