Using Microbubble Subharmonics to Non-Invasively Measure Internal Pressures

Abstract

Hydrostatic pressure measurements give healthcare providers essential information regarding patient health and are necessary for the diagnosis and treatment of many diseases. The current gold standard for these measurements is a catheterization procedure which is invasive and costly. A promising non-invasive alternative is to use ultrasound and microbubbles to monitor hydrostatic pressure by detecting changes in the subharmonic frequency component of the microbubble response to ultrasound. However, the relationship between subharmonic signal and hydrostatic pressure varies widely across microbubble formulations, experimental setups and acoustic parameters, limiting clinical implementation of the technique. SonoVue, a clinically approved contrast agent, is a promising option for this purpose, but there has been limited exploration of its hydrostatic pressure sensitivity compared to other agents, especially at low acoustic pressures. This thesis presents several investigations into the relationship between subharmonic signal and hydrostatic pressure utilizing both a single-element transducer bench-top setup and a modified clinical ultrasound system. Chapter 1 introduces subharmonic imaging and its utilization for noninvasive hydrostatic pressure measurements. In Chapter 2, a single-element transducer bench-top setup was established to characterize the subharmonic response of SonoVue across a range of physiologically relevant hydrostatic pressures and acoustic parameters. In Chapter 3, optimal acoustic parameters were implemented on a clinical scanner and the mode’s sensitivity to hydrostatic pressure across a range of acoustic pressures, microbubble concentrations, and agent formulations was evaluated. Chapter 4 concludes with a summary of the accomplishments and future directions of the work. Together, these investigations represent a meaningful step toward a standardized, non-invasive framework for hydrostatic pressure estimation using clinically approved tools.