PROJECT SUMMARY / ABSTRACT More than 1 million patients in the U.S. undergo cardiac catheterization each year, and more than 200k of these patients have stable coronary artery disease. Approximately 10% of patients with stable disease will experience a major adverse event within a given two year period. Current imaging approaches based on independent indicators have largely failed to predict adverse events, thus there are currently no techniques capable of determining which patients are likely to experience adverse events such as myocardial infarction (MI). The ability to make treatment decisions based on comprehensive, simultaneous measurements of the complete coronary environment—including biomechanics and hemodynamics—rather than independent indicators could improve outcomes and reduce costs in at-risk patients. This project proposes to develop a very small, forward-viewing ultrasound catheter capable of simultaneously interrogating the comprehensive 3D coronary environment in order to guide decisions in the cardiac catheterization lab. Specifically, the CoSHIS catheter (Composition, Structure, and Hemodynamics in Intermediate Stenoses) will simultaneously quantify the coronary environment (including plaque mechanics and blood flow) in real-time 3D, unlike current imaging approaches that seek to identify independent indicators of plaque rupture. In order to enable this multi- functional quantification to guide treatment decisions, technological development is needed to ensure accurate performance in a very small form factor. By leveraging recent advances in ultrasound imaging technology including array design, data reconstruction, high frame rate image formation, and internal flow catheters designed to minimize flow disturbance, this project will develop the core technology on for 4D mapping of the coronary mechanical enviornment This technology for imaging-guided intervention in the cardiac catheterization lab will unite expertise in ultrasound imaging and technology development, imaging-based computational modeling, animal models of coronary artery disease, and interventional cardiology, and will be developed according to the following three Aims: 1. Development of a forward-viewing system for 3D intravascular ultrasound (US) imaging of lesion morphology, hemodynamics, and plaque composition. 2. Validation of novel ultrasound measurement technology with established techniques including computed tomography (CT), computational fluid dynamics (CFD) based on angiography, and virtual histology intravascular ultrasound. 3. Evaluation of simultaneous US-based measurement in animal models of intermediate stenoses with validation using established techniques.

PROJECT NARRATIVE >200k people in the U.S. undergo cardiac catheterization for their stable coronary artery disease (CAD) each year to stratify risk of major adverse cardiac events in a patient population having a wide range of outcomes, with annual mortality rates varying by a factor of 6 between “low risk” and “high risk” stable CAD patients. Current imaging and non-imaging techniques for risk stratification and prediction of adverse events (such as myocardial infarction) based on independent indicators such as lesion structure and plaque composition are largely unsuccessful. By leveraging recent advances in ultrasound transducer array design, data reconstruction, high frame rate image formation, and catheter design, this project will develop an ultrasound imaging catheter designed to characterize the comprehensive coronary enviornment based on the full mechanics and hemodynamics surronding the stenosis.