Pilot Project Abstract - Owen McCarty, PhD
Owen McCarty, PhD, Assistant Professor of Biomedical Engineering at OHSU: “Contrast-enhanced ultrasound imaging of thrombotic thrombocytopenic purpura”
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, multisystemic disorder resulting from the formation of platelet microthrombi, which in turn results from the incomplete processing of the adhesive protein von Willebrand factor (VWF). In TTP, VWF-induced platelet aggregates form in the microcirculation throughout the body, causing partial occlusion of vessels and leading to organ ischemia, thrombocytopenia, and erythrocyte fragmentation. Presently, the TTP mortality rate is about 95% for untreated cases. In contrast, the survival rate is 80-90% with early diagnosis and treatment with plasma infusion and plasma exchange. However, at present, the detection of TTP relies on clinical diagnosis of a pentad of signs and symptoms, as there is no pathognomonic laboratory assay for TTP. Diagnostic medical imaging has been explored recently, to enable the detection of underlying pathophysiologic cellular and molecular processes of diseases. We propose to create novel, targeted contrast agents that specifically bind to TTP-related antigens. We hypothesize that non-invasive detection of VWF, the principal adhesive protein involved in initiating platelet microthrombi formation, could be used to diagnose TTP. The goal of our research is to develop a contrast-enhanced ultrasound (CEU) molecular imaging method that targets to VWF via the high-affinity platelet receptor glycoprotein (GP) Ib.