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Sensitivity of the subharmonic responses from contrast microbubbles to ambient pressure

Microbubbles are well-known ultrasound contrast agents which can produce nonlinear oscillation leading to harmonic and subharmonic responses. There has been an interest in utilizing this phenomenon for noninvasive pressure estimation and its use in diagnosis of diseases such as portal hypertension. The subharmonic response of a microbubble display three different regimes with increasing excitation: occurrence, growth, and saturation. In this study, subharmonic responses of lipid-shelled microbubbles were investigated with varying ambient pressures at different excitation parameters. We observed that subharmonic sensitivity to ambient pressure varied differently in different excitation ranges. We also noted that applying overpressure could induce subharmonic generation where there was no subharmonic without overpressure. At occurrence stage, the sensitivity of subharmonic to ambient pressure was significantly higher. This property can be utilized for improved pressure estimation with high sensitivity even at low acoustic excitation.