Remote Intravascular Pressure Sensing using Ultrasound

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PROJECT SUMMARY Many of the clinically significant complications of liver cirrhosis arise as a consequence of increased portal hypertension. Direct measurement of portal venous pressures is invasive and requires significant procedural experience. Therefore, an accurate and noninvasive method for measurement of portal venous pressure has the potential to reduce risk and enable clinicians to improve the routine workup of patients with liver disease. To that end, our group has exciting data that suggests remote pressure sensing in tissue can be performed using a novel contrast agent and custom technology we have termed tissue intravascular pressure estimation using ultrasound (TIPE-US). A recent advance was in the development of a phase-change contrast agent (PCCA), which is a stabilized liquid nanodroplet under ambient conditions but can be selectively activated using pulsed ultrasound energy to undergo a phase transition into a highly echogenic microbubble detectable using ultrasound imaging. Several studies by our group have consistently shown that the ultrasound energy required for PCCA activation is highly linear and dependent on the hydrostatic pressure of the surrounding fluid. Therefore, we hypothesize that these PCCAs and real-time ultrasound imaging techniques can be used for remote intravascular pressure sensing and detection of portal hypertension. The overarching goal of the proposed research project is to develop a next-generation TIPE-US imaging system and method for remote pressure sensing in vascularized tissue. The first aim of this project is to implement new TIPE-US functionality and feedback control on a programmable ultrasound scanner. In the second aim, we will evaluate the use of custom and monodisperse PCCAs to maximize sensing signal generation and quantification during TIPE-US imaging. We will also conduct the first in vivo tests of TIPE-US using an established animal model portal hypertension.