A novel numerical approach to elucidate experimental scatter in portal pressure measurement using ultrasound contrast agent

The use of ultrasound contrast agents (UCAs) for estimating portal pressure has recently gained attention due to its clinical promise, yet variability in acoustic amplitude poses challenges. UCAs contain microbubbles (1-10 µm in diameter), and understanding their acoustic response is essential to address this variability. However, systematic exploration of factors influencing microbubble behavior remains limited in current literature. This paper introduces a novel finite element analysis-based framework for portal pressure estimation, bridging key gaps. Developed in two stages, the model first captures the subharmonic response of a single bubble to an acoustic excitation of 50 kPa at 4 MHz, highlighting the influence of bubble size on resonance frequency. In the second stage, single-bubble responses are extended to analyze how microbubble population, size, and spatial distribution affect portal pressure estimation. For the first time, this study elucidates the experimental scatter in pressure measurements through a comprehensive consideration of these variables, offering new directions for UCA-based clinical pressure estimation in applications such as portal and cardiac pressure assessment.