Correlation Between Portal Vein Pressure and Subharmonic Scattering Signals From SonoVue Microbubbles in Canines

The current gold standard for the clinical diagnosis of portal hypertension (PH) is an invasive and indirect estimation of portal vein pressure (PVP). Therefore, the need for a non-invasive PVP measurement method is urgent. Subharmonic scattering of ultrasound contrast agent (UCA) microbubbles is under investigation in clinical research as a pressure indicator. However, the driving acoustic pressure must be optimized to improve the ambient pressure sensitivity of the subharmonic amplitude for different UCAs. In this study, for the first time, we obtained the relationship between the PVP and the amplitude of the subharmonic signal scattered from SonoVue microbubbles by using two canines to build the PH model. The results revealed a desirable linear correlation between the subharmonic amplitude and PVP (<20 mmHg) at the incident acoustic pressure of 453 kPa (r = -0.910, p < 0.005; sensitivity: -2.003 dB/mmHg); this was one order of magnitude higher in sensitivity than that of the in vitro case with a detectable pressure variation of approximately 1 mmHg. This indicates the feasibility of using UCA microbubbles to accurately measure low ambient pressures in vivo and further exhibits the potential of the method for non-invasive pressure estimation in clinical applications.