Design of Phantoms and Targeted Agents for Ultrasound Contrast Imaging of Microvessels and Fibrin Clots

Abstract

Venous thromboembolisms (VTE) are common cardiovascular events including deep vein thrombosis and pulmonary embolism. Early diagnosis and management of VTEs can significantly improve patient quality of life and mortality. Such clinical insights made possible through medical imaging are critical for clinicians to manage patient risk and treatment efficacy. As the linchpin in point of care medical imaging, Ultrasound (US) is the workhorse modality in patient diagnosis and treatment monitoring within the clinic. However, specific detection of the molecule fibrin which is the current clinical treatment target for VTEs remains elusive for US in the clinic. In this dissertation, I designed an ultrasound contrast agent with fibrin targeting properties. The baseline contrast agent was used to test a novel in vitro flow phantom with tissue mimicking characteristics to validate a contrast specific super-resolution ultrasound algorithm. The contrast agent was further modified to target fibrin leveraging the existing fibrin targeting properties of a therapeutic agent and demonstrated to be adherent to a fibrin surface as well as enhancing the detection of fibrin surfaces when imaging with a clinical scanner. Finally, a comparison study was performed examining the fibrin targeting ligand options in ultrasound literature and to further investigate the robustness of using anti-fibrin therapeutics for pure imaging applications in more physiologically realistic flow scenarios. This work aims to raise current developments in ultrasound molecular imaging to address the existing clinical need to detect fibrin as a treatment target. Baseline MBs were shown to be versatile enablers for specialized contrast imaging applications. Moreover, the significant improvement to ultrasound signal using fibrin targeting contrast confirms that ultrasound molecular imaging can be a robust solution to improve fibrin detection. Finally, the insights gained through comparing the existing MB targeting strategies provides new directions to consider for future development of fibrin targeting contrast.