? Inflammation plays a critical role in the development and progression of vascular disease, including atherosclerosis. Strategies for visualizing the inflammatory process in vivo can help elucidate the timing of cellular infiltration, the signals that recruit inflammatory cells, and the role of these cells in the pathogenic process. A greater understanding of these mechanisms, through the application of sensitive imaging tools to this disease, will aid in the evaluation and development of effective therapies. The overall goals of this research are to develop and evaluate a sensitive and reliable platform for imaging vascular inflammation in relevant rodent models of disease and to use this technology to help understand the biological basis of atherosclerosis formation in order to guide novel approaches to therapy. ? ? Toward this end, we use two complementary imaging technologies - in vivo bioluminescence imaging and MRI. Bioluminescence has high sensitivity, is quantitative, and can reveal gene regulatory pathways. MRI provides high-resolution vascular imaging and tissue characterization and can image inflammatory cells using ultra-small superparamagnetic iron-oxide contrast agents (USPIOs). ? ? Specific Aims: 1) In vivo bioluminescence imaging of inflammatory cell trafficking to the vessel wall. ? 2) In vivo MRI of inflammatory cell trafficking to the vessel wall. ? 3) Bioluminescence and MRI of vascular inflammation in response to interventions. ? ? We have directed these studies to rodent models of vascular disease as they are ideal for studying the underlying molecular and cellular biology of disease progression and response to therapy. The long-term goal of our research is to improve the detection, evaluation, understanding, and treatment of human atherosclerotic disease. (End of Abstract) ? ? ?
