A Clinical Perspective and Review on the Use of the Subharmonic Signal of Ultrasound Contrast Agents for Noninvasive...

Changes in physiological pressures play a key role in the development and progression of human disease processes. Thus, the assessment of pressures within blood vessels and other bodily compartment is crucial in the diagnosis and management of multiple medical conditions. Presently, techniques for pressure measurement are invasive or have limited accuracy and scope of assessment. Utilizing the subharmonic signal of ultrasound contrast agents offers a promising solution that could address these limitations. After the initial development of this technology in the late nineties, further investigation has brought subharmonic pressure estimation from in vitro exploration to attempts at clinical implementation. However, lack of availability of subharmonic imaging on most clinical scanners, and variability of subharmonic response with different contrast agents have impeded clinical acceptance and widespread use of this modality. This review examines subharmonic imaging and the use of ultrasound contrast agents for estimating physiological pressures, particularly in the heart and portal venous system. A focus is placed on clinically relevant physiologic pressures and their existing measurement approaches, the physics of subharmonic signal generation, in vitro studies demonstrating key findings, and more recent clinical trials. The review also highlights present limitations and future research directions that may help advance clinical translation.