Effects of Different Gas Cores on the Ambient Pressure Sensitivity of the Subharmonic Response of SonoVue

Objective: Subharmonic Aided Pressure Estimation (SHAPE) is a noninvasive technique for estimating organ-level blood pressure using the strong correlation between the subharmonic signal and ambient pressure. The compressible gas core of microbubbles enables them to generate linear and nonlinear acoustic responses when exposed to ultrasound. Here, the sulfur hexafluoride (SF₆) gas core of SonoVue (known as Lumason in the United States), a clinical contrast agent, was exchanged with a perfluorobutane (PFB) core to investigate its effect on the SHAPE response.

Methods: Excitations of 25-700 kPa peak negative pressure (PNP) and 3 MHz transmission frequency were used to study in vitro the effects of overpressure changes ranging from 5 to 25 kPa (37-186 mm Hg).

Results: Unlike SonoVue with SF₆, at low PNPs (<400 kPa), SonoVue with a PFB gas core exhibited no subharmonic at the atmospheric pressure, but during pressurization, a stable subharmonic response (maximum of 25 dB at 100 kPa PNP and 20 kPa Overpressure) appeared. SonoVue with a PFB gas core showed an increase in subharmonics with overpressure at high PNPs (>400 kPa), which was not observed before in normal SonoVue or other lipid microbubbles. With negligible size distribution difference between these two microbubbles, these effects on subharmonic generation are likely due to the gas core, casting new light on the mechanism by which ambient overpressure affects subharmonic.

Conclusion: This study may inform future SHAPE technique developments.