Ambient pressure dependent subharmonic response of contrast microbubbles for blood pressure estimation using ultrasound imaging

Subharmonic Aided Pressure Estimation (SHAPE) is a non-invasive method to measure blood pressure inside critical organs using ultrasound imaging. This method utilizes the strong sensitivity of subharmonic response from ultrasound contrast microbubbles to the change in the ambient pressure i.e. blood pressure. The subharmonic generation is known to be a threshold phenomenon with the threshold depending on the acoustic parameters as well as the physical properties of bubbles such as size, resonance frequency, and shell initial condition. In this study, we characterized the subharmonic generation and its sensitivity to the ambient pressure for different microbubbles over 25 – 700 kPa acoustic pressures, 3 MHz frequency, and hydrostatic pressure range of 0-25 kPa. The subharmonic showed different trends of increase and decrease with hydrostatic pressure depending on the maximum overpressure magnitude, number of pressure cycles, and initial subharmonic amplitude (before and after threshold). These findings could play important role in accurate determination of subharmonic correlation with ambient pressure resulting in improved pressure estimation in SHAPE.