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

To our knowledge, despite several studies on the propagation velocity of pressure wave fields through ultrasound contrast agents (UCAs) have been conducted, the variation of propagation velocity between the fundamental and second harmonic component generated during the propagation of ultrasound through UCAs has not been studied yet. For this purpose, transmission and backscattering measurements of pressure wave fields propagating through gelatin phantoms containing cylindrical cavities of different diameter, filled with different concentrations [0 to 240 μL/L] of SonoVue® contrast agent, are conducted. Different frequencies [2, 2.5, and 3 MHz] and mechanical indices [0.05, 0.1, and 0.2] are investigated. Moreover, measurements obtained with Definity® contrast agent are also 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 delay increases with increasing microbubble concentration and diameter of the cavity, it depends on mechanical index and frequency, and, most importantly, it is not observed in the absence of UCAs. These results may be relevant for contrast-enhanced ultrasonography, providing new possibilities to increase contrast-to-tissue ratios and to quantify UCA concentrations