Subharmonic Scattering of SonoVue Microbubbles Within 10–40-mmHg Overpressures In Vitro

Ultrasound contrast agent microbubbles are considered promising sensors to measure portal vein pressure noninvasively. In this study, we investigated the subharmonic scattering power and optimal incident acoustic pressure of SonoVue microbubbles (concentration: $1~\mu \text{L}$ /mL 0.9% NaCl solution) in the ambient pressure range of 10–40 mmHg with 10-mmHg increments at a temperature of 25 °C. The results demonstrated that the subharmonic response of the SonoVue microbubbles existed in three stages: the first growth stage (40–300 kPa), saturation (300–400 kPa), and the second growth stage (400–540 kPa). In the first growth stage, the subharmonic amplitude increased with ambient pressure. However, while the ambient pressure increased, the subharmonic amplitude decreased in the second growth stage. The best correlation of the subharmonic amplitudes with the ambient pressures was obtained at a high incident acoustic pressure of 520 kPa (sensitivity: 0.15 dB/mmHg, ${r}^{{{2}}} =0.99$ , and root-mean-square error = 0.49 mmHg), which indicated that the subharmonic signals in the second growth stage might be suitable for estimating low ambient pressures. The results presented in our study may pave the way for portal vein pressure estimation using SonoVue microbubbles as sensors in clinical applications.

I. Introduction

Portal hypertension (PH) is a severe symptom of chronic liver diseases [1] and is associated with serious clinical complications, such as variceal hemorrhage, ascites, hepatic encephalopathy, and failure [2]. According to clinical practice guidelines, measuring the portal pressure is crucial for developing clinical management and evaluating treatment efficacy [1], [3]. The normal pressure of the portal vein ranges from 13 to 24 cm H₂O (9.6–17.6 mmHg) [2]. The gold standard for monitoring portal pressure is the measurement of the hepatic venous pressure gradient (HVPG) through hepatic vein catheterization. However, hepatic vein catheterization with the measurement of the HVPG is an invasive and indirect method, and complications, such as bleeding, bile leakage, and infection, may be caused in a small subset of patients [4]. Whether patients with PH can be reliably identified using noninvasive approaches remains a domain of intense investigation [2].