Towards reliable subharmonic-aided pressure estimation: Simulation and experimental validation of microbubble dynamics

This study examines the reliability of subharmonic-aided pressure estimation (SHAPE) using polydisperse microbubbles. SHAPE utilizes the subharmonic response of ultrasound contrast agent microbubbles to estimate pressure non-invasively. Despite its potential, gaps in theoretical understanding and experimental inconsistencies with polydisperse microbubbles necessitate further investigation. This research explores the impact of microbubble distribution, excitation parameters, and contrast-enhanced ultrasound imaging modes on SHAPE’s signal consistency, measurement linearity, and sensitivity. A one-dimensional microbubble population model was developed to simulate microbubble behavior and the Hilbert transform demodulation technique was applied for subharmonic analyses. Variability in SHAPE was further assessed through flow phantom experiments using Sonazoid agents and a commercial SHAPE scanner. Findings indicate that bubble distribution in both size and location, microbubble interactions, and CEUS imaging modes significantly influence subharmonic responses. An excitation frequency of 3.5 MHz is recommended for robust SHAPE. Monte Carlo simulations confirmed the inherent variability of subharmonic amplitude signals due to dynamic bubble distributions. Using monodisperse microbubbles enhanced SHAPE sensitivity and consistency, without markedly reducing signal variability. These results underscore the necessity of further research to optimize SHAPE for clinical applications, focusing on microbubble characteristics and excitation conditions to enhance consistency and reliability.