The goal of this Phase I STTR project is to construct, optimize, and test a clinically viable intravascular near-infrared fluorescence/intravascular ultrasound (NIRF-IVUS) imaging catheter for simultaneous molecular and structural diagnosis of coronary artery disease (CAD). CAD is a worldwide leading cause of death and disability, including acute myocardial infarction, congestive heart failure, and sudden cardiac death. Molecular processes such as inflammation drive devastating CAD and stent complications, but are largely invisible to contemporary clinical imaging methods. The ability to image and quantify molecular processes will greatly improve our ability to improve CAD patient risk stratification, improve percutaneous coronary intervention (PCI) procedures at the point of care, optimally tailor CAD and stent pharmacotherapies (including PCSK9 inhibitors), and streamline new CAD and coronary stent product development. Intravascular Imaging Inc. (i3) in collaboration with MGH has developed novel and innovative intravascular imaging systems that combine high-resolution IVUS, the current anatomical imaging standard of care, with NIRF molecular imaging, a powerful new molecular imaging approach. However, our prototype intracoronary NIRF-IVUS catheter is too large (4.5 French/1.5 mm) for routine clinical coronary imaging. In order to enable clinical translational and commercialization of intracoronary NIRF imaging, this Phase I STTR objective is design, construct, and miniaturize a NIRF-IVUS imaging catheter for imaging smaller coronary arteries and to test it in vivo.
In Aim 1, i3 will engineer miniaturized NIRF-IVUS catheters for use in coronary arteries (<3.6French/1.2 mm diameter).
In Aim 2, MGH will test the NIRF-IVUS catheters in swine coronary arteries to obtain simultaneous in vivo coronary molecular-structural imaging of plaque inflammation and plaque burden. The anticipated results of this proposal will generate a highly translatable, coronary artery NIRF-IVUS imaging catheter that can simultaneously image plaque inflammation based on NIRF molecular contrast, and plaque structure based on IVUS. Following successful completion of this project, i3 will submit an SBIR/STTR Phase II application to construct GMP grade intracoronary NIRF-IVUS coronary artery imaging catheters and systems, with the goal of obtaining FDA IDE approval for first-in-human studies. The long-term objective of intracoronary NIRF-IVUS is to improve the outcome of CAD patients entering the cardiac catheterization laboratory by: A) Better risk-stratifying patients at risk of coronary plaque or stent complications; B) Identifying the higher-risk CAD patients likely to benefit from PCSK9 inhibitor therapy; and C) Comprehensively assessing the molecular and structural efficacy of novel CAD pharmacotherapeutics and new stents in Phase IIa/IIb and Phase III clinical trials.
New methods are needed to identify patients that will suffer heart attacks and sudden cardiac death from coronary plaque and stent complications. This Project will, for the first time, combine two intravascular imaging methods based on light (near-infrared fluorescence) and sound (ultrasound) into a clinically and commercially viable catheter system (NIRF-IVUS) that can simultaneously image the biology and structure of coronary artery disease. The new knowledge gained from intracoronary NIRF-IVUS will eventually better identify patients at higher risk of coronary plaques and stent complications, guide the selection of the medicines to reduce these complications, and provide a new approach to streamline the development of new drugs and stents designed to treat coronary disease.