Clinical thrombosis has a series and wide-ranging impact on the health of millions of patients, as occurs with heart attacks, strokes, venous thrombo-embolism and disseminated intravascular coagulation. The experimental study of thrombosis requires a consideration of many converging elements within a single physical locale - an intravascular thrombus. The interplay of coagulation factors and platelet activation/accumulation is incompletely understood, as well as the relative involvement of each element in arterial or venous or microvascular thrombosis - distinct entities with different mechanisms of thrombus development and resolution. To overcome the high cost and labor-intensive aspects of recently developed systems for thrombosis study, and to adapt such a system to large-vessel (both artery and vein) thrombosis investigations, the following proposed study will develop a low-cost imaging system for continuous quantitative evaluation of a developing thrombus. Murine large arteries and veins (up to 1 mm in diameter) will be imaged with a low-light digital camera with video development capabilities. Thrombus targets will be labeled with fluorophores (attached to systemically circulating platelets or fibrinogen, or antibodies to coagulation cascade enzymes) to permit monitoring of incorporation into a standardly induced thrombus (using thrombosis models developed and published by the PI). Low-cost excitation light sources (e.g., LEDs or laser pointers) will be matched to the excitation wavelength of each fluorophore, using band-pass filters to permit image capture of emission wavelengths for each fluorophore. The system will undergo rigorous ex vivo testing, followed by in vivo analyses, directly comparing outcomes with established methods for thrombus quantitation. The findings will demonstrate the feasibility of developing such a system and show its applicability to the investigation of experimental thrombosis. This imaging methodology may have a capacity for future adaptation to clinical thrombosis imaging. ? ? ?
| Cooley, Brian C; Herrera, Anthony J (2013) Cross-modulatory effects of clopidogrel and heparin on platelet and fibrin incorporation in thrombosis. Blood Coagul Fibrinolysis 24:593-8 |
| Maroney, Susan A; Cooley, Brian C; Ferrel, Josephine P et al. (2012) Absence of hematopoietic tissue factor pathway inhibitor mitigates bleeding in mice with hemophilia. Proc Natl Acad Sci U S A 109:3927-31 |
| Maroney, Susan A; Cooley, Brian C; Ferrel, Josephine P et al. (2011) Murine hematopoietic cell tissue factor pathway inhibitor limits thrombus growth. Arterioscler Thromb Vasc Biol 31:821-6 |
| Cooley, Brian C (2011) In vivo fluorescence imaging of large-vessel thrombosis in mice. Arterioscler Thromb Vasc Biol 31:1351-6 |
