New imaging methods are urgently needed to identify and to guide treatment of high-risk atherosclerotic plaques before lead to their devastating complications of myocardial infarction and stroke. While imaging technologies have made progress in illuminating plaque volume and plaque structure, they do not routinely visualize aspects of plaque biology such as inflammation, a key determinant of plaque complications. Imaging of molecular and cellular detail in atherosclerosis offers a transformative approach to improve the biological diagnosis, risk stratification, and treatment of high-risk plaques. In addition, molecular imaging of atherosclerosis can identify new pharmacotherapies that favorably alter plaque biology (e.g. anti-inflammatory), with the potential to streamline drug development and to efficiently bring new therapies into the clinic. At present however, existing molecular imaging approaches are unable to routinely visualize high-risk plaques in human coronary arteries. The long-term objective of this grant proposal is to develop new human coronary artery-targeted intravascular near-infrared fluorescence (NIRF) molecular imaging strategies to identify atherosclerotic plaques responsible for myocardial infarction. Recently, a one-dimensional, manual pullback intravascular NIRF sensing catheter established the feasibility of imaging plaque inflammation through blood in coronary-sized vessels. The Proposal now aims to develop a next-generation intravascular NIRF catheter capable of true two- dimensional NIRF imaging in human coronary-sized arteries in vivo.
Specific Aim 1 will design, construct, and validate a rotational and automated pullback NIRF catheter to enable 360-degree and longitudinal 2D vessel wall imaging of atheroma inflammation in rabbit aortic vessels, an advance over existing limited-arc spectroscopic NIRF catheters.
Specific Aim 2 will utilize the validated NIRF rotational catheter to assess anti- inflammatory (statin) effects in experimental atherosclerosis, extending the in vivo imaging armamentarium to assess the efficacy of therapeutics for vascular disease.
Specific Aim 3 investigates the ability of indocyanine green, an FDA-approved diagnostic imaging agent, to serve as an inflammation-targeted intravascular NIRF imaging agent for atherosclerotic plaques.
Specific Aim 4 tests the NIRF catheter's ability to perform molecular imaging directly in experimental coronary arteries in vivo, with the goal of accelerating catheter translation into the clinical arena. The Proposal builds on established large animal catheter-based imaging efforts in the Investigator's laboratory and leverages established engineering, imaging, and biological expertise from a multidisciplinary team.
New imaging methods are urgently needed to identify high-risk atherosclerotic plaques before they cause heart attacks. This research project is directed at developing new fluorescence catheters and approaches for imaging of high-risk plaques in human coronary-sized arteries. The results from this project could enable the development of clinical fluorescence imaging strategies to reduce heart attacks.
|Mulder, Willem J M; Jaffer, Farouc A; Fayad, Zahi A et al. (2014) Imaging and nanomedicine in inflammatory atherosclerosis. Sci Transl Med 6:239sr1|
|Sawada, Naoki; Jiang, Aihua; Takizawa, Fumihiko et al. (2014) Endothelial PGC-1? mediates vascular dysfunction in diabetes. Cell Metab 19:246-58|
|Press, Marcella Calfon; Jaffer, Farouc A (2014) Molecular intravascular imaging approaches for atherosclerosis. Curr Cardiovasc Imaging Rep 7:9293|
|Hara, Tetsuya; Truelove, Jessica; Tawakol, Ahmed et al. (2014) 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables the detection of recurrent same-site deep vein thrombosis by illuminating recently formed, neutrophil-rich thrombus. Circulation 130:1044-52|
|Sadat, Umar; Jaffer, Farouc A; van Zandvoort, Marc A M J et al. (2014) Inflammation and neovascularization intertwined in atherosclerosis: imaging of structural and molecular imaging targets. Circulation 130:786-94|
|Jaffer, Farouc A; Verjans, Johan W (2014) Molecular imaging of atherosclerosis: clinical state-of-the-art. Heart 100:1469-77|
|Osborn, Eric A; Jaffer, Farouc A (2013) The advancing clinical impact of molecular imaging in CVD. JACC Cardiovasc Imaging 6:1327-41|
|Verjans, Johan W; Jaffer, Farouc A (2013) Biological imaging of atherosclerosis: moving beyond anatomy. J Cardiovasc Transl Res 6:681-94|
|Taqueti, Viviany R; Jaffer, Farouc A (2013) High-resolution molecular imaging via intravital microscopy: illuminating vascular biology in vivo. Integr Biol (Camb) 5:278-90|
|Osborn, Eric A; Jaffer, Farouc A (2013) Imaging atherosclerosis and risk of plaque rupture. Curr Atheroscler Rep 15:359|
Showing the most recent 10 out of 20 publications