Non-Invasive Pressure Estimation Using Ultrasound Imaging and Phase Change Contrast Agents

Pulsed ultrasound (US) energy can be used to activate a phase-change contrast agent (PCCA) from a liquid nanodroplet state to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure, and temperature of the surrounding media, applied frequency of the US transducer, and size of the PCCA. This research explores the relationship of these parameters on the activation threshold as a potential non-invasive pressure measurement and foundation for a unique technology our research group is developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). This thesis outlines development of TIPE-US using a programmable US research scanner for both PCCA activation and MB detection. An automated pressure sweep was applied to acquire US images at each hydrostatic pressure increment. The activation threshold required to convert PCCA from liquid to gaseous state was recorded for various hydrostatic pressures (10 to 100 mmHg) applied to PCCA samples and the effect of aforementioned parameters were demonstrated. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration. Although, theoretically the activation threshold decreases as diameter of the PCCA increases, experimentally this effect was not discernible.