The Effects of Hydrostatic Pressure on the Subharmonic Response of SonoVue and Sonazoid

It has been previously established that the subharmonic signal of microbubble ultrasound contrast agents follows an inverse linear relationship with the ambient hydrostatic pressure. However, contradictory results have been reported for SonoVue (Bracco Spa, Milan, Italy). Therefore, the aim of this study was to investigate the subharmonic response of SonoVue across a range of physiologically-relevant hydrostatic pressures (10-220 mmHg), and to compare it with Sonazoid (GE, Oslo, Norway). A modified GE Logiq 9 scanner was used to acquire the subharmonic signals from Sonazoid and SonoVue in a sealed water tank. In addition, the Ultrasound Advanced Open Platform (ULA-OP) was used to acquire the subharmonic signal of SonoVue at 0-200 mmHg in a cell culture cassette over approximately 3 min. Sonazoid showed an inverse linear relationship between subharmonic amplitude and hydrostatic pressure (slope -0.11 dB/mmHg; r = -0.81), as expected. SonoVue exhibited an increase in subharmonic amplitude from 0-100 mmHg hydrostatic pressure (slope 0.06 dB/mmHg, r = 0.81), a plateau between 100-140 mmHg, and a decrease from 140-220 mmHg (slope -0.26 dB/mmHg, r = -0.98). The subharmonic amplitude of SonoVue increased over 3 min at 0 and 25 mmHg hydrostatic pressure, did not change with time at 50-100 mmHg, and decreased over time at 125-200 mmHg. However, the effects of time on the subharmonic amplitude of SonoVue were smaller than the effects of hydrostatic pressure. The subharmonic response of SonoVue to hydrostatic pressure differs from Sonazoid and other microbubble ultrasound contrast agents.