Ambient Pressure Sensitivity of Subharmonic Vibrating Single Microbubbles

Objective: The response of ultrasound contrast agents is sensitive to ambient pressure, especially via their scattered subharmonic signal, which makes them a promising candidate for non-invasive pressure measurements in vivo. This work aimed to understand the sensitivity to ambient pressure of subharmonic oscillations from single microbubbles. Methods: The subharmonic oscillation amplitude of single microbubbles in response to varying ambient pressure was studied both experimentally and numerically. In experiment, approximately 2200 single microbubbles from a monodisperse population were measured at a driving frequency close to twice their resonance frequency. Results: The results of the numerical simulations and experiments show that a pressure change leads to a small size change in the bubble that then changes the lipid packing density, and with that the stiffness of the bubble shell. Conclusion: The dependency of subharmonic oscillation amplitude to changes in ambient pressure can be explained by a shift in the resonance frequency of the bubble as a function of ambient pressure. The subharmonic response increases with ambient pressure when the resonance frequency shifts toward half the driving frequency and decreases when the resonance frequency shifts away from half the driving frequency. These findings help to understand non-invasive pressure sensing through subharmonic ultrasound imaging.