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.
|Stein-Merlob, Ashley F; Hara, Tetsuya; McCarthy, Jason R et al. (2017) Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging. Circ Cardiovasc Imaging 10:|
|Hara, Tetsuya; Ughi, Giovanni J; McCarthy, Jason R et al. (2017) Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo. Eur Heart J 38:447-455|
|Verjans, Johan W; Osborn, Eric A; Ughi, Giovanni J et al. (2016) Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green. JACC Cardiovasc Imaging 9:1087-1095|
|Stein-Merlob, Ashley F; Kessinger, Chase W; Erdem, S Sibel et al. (2015) Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study. Theranostics 5:1317-27|
|Kessinger, Chase W; Kim, Jin Won; Henke, Peter K et al. (2015) Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring. PLoS One 10:e0116621|
|Cui, Jie; Kessinger, Chase W; McCarthy, Jason R et al. (2015) In vivo nanoparticle assessment of pathological endothelium predicts the development of inflow stenosis in murine arteriovenous fistula. Arterioscler Thromb Vasc Biol 35:189-96|
|Osborn, Eric A; Jaffer, Farouc A (2015) Imaging inflammation and neovascularization in atherosclerosis: clinical and translational molecular and structural imaging targets. Curr Opin Cardiol 30:671-80|
|Ughi, Giovanni J; Verjans, Johan; Fard, Ali M et al. (2015) Dual modality intravascular optical coherence tomography (OCT) and near-infrared fluorescence (NIRF) imaging: a fully automated algorithm for the distance-calibration of NIRF signal intensity for quantitative molecular imaging. Int J Cardiovasc Imaging 31:259-68|
|Jaffer, Farouc A; Verjans, Johan W (2014) Molecular imaging of atherosclerosis: clinical state-of-the-art. Heart 100:1469-77|
|Mulder, Willem J M; Jaffer, Farouc A; Fayad, Zahi A et al. (2014) Imaging and nanomedicine in inflammatory atherosclerosis. Sci Transl Med 6:239sr1|
Showing the most recent 10 out of 38 publications