Heart disease is the leading cause of death in the US; the most prevalent type of heart disease is caused by atherosclerosis, the thickening of the vessel wall and creation of atherosclerotic plaque. Intravascular optical coherence tomography (IV-OCT) has enabled the imaging of coronary artery structures with un- precedented detail, and can be used to evaluate the response to percutaneous coronary intervention when treating atherosclerotic lesions. However, there remains a significant need to assess plaque vul- nerability: the determination of which mild lesions are likely to produce cardiac events in the future, and thus require immediate preventative interventional measures. Among lesion types, thin-cap fi- broatheromas (TCFA) are of particular concern since they are believed to be at increased risk of rup- ture; however, studies have found that only a fraction of TCFAs rupture. Although the likelihood of rupture has been linked to its mechanical stability, its chemical composition, and its microstructure, there is currently no technology capable of the biomechanical profiling of plaques in individual patients during intervention [without the need for time-consuming finite element modeling (FEM)] and the available methods for determining composition either lack specificity or spatial resolution. To address this significant need unmet by current intravascular imaging technology, we will develop an all-optical imaging platform that will profoundly broaden the access to accurate biomechanical, chemi- cal and microstructural profiling of coronary plaques in individual patients. Our novel platform will en- able a transformational leap in the current capability for comprehensive plaque characterization, in- cluding the assessment of plaque composition and vulnerability. We will leverage new ultra-fast laser sources to develop IV-OCT at 2,000 frames per second, enabling a host of powerful post-processing techniques that will enhance comprehensive characterization of plaques. In Aim 1 we will develop the enabling hardware to realize high-speed intravascular imaging. In Aim 2 we will develop hardware and signal processing to enable microstructural profiling at the 10×302 µm3 (depth×lateral) scale, chemical profiling at the 80×802 µm3 scale, and biomechanical profiling at the 60×602 µm3 scale in an all-optical technique without the need for FEM. In Aim 3 we will develop a novel validation platform based on a soft-robotics cardiac simulator of the biomechanical environment of the human beating heart. Our single imaging platform will facilitate clinical studies to determine the parameters of plaque vulner- ability, opening the door to the identification of optimal treatment strategies. Initially, it will become an invaluable research tool in atherosclerosis; later, it will have the potential to guide intervention in indi- vidual patients. After completion of the technological developments at the end of the proposed funding cycle, our platform will be ready for testing in human subjects.

The most prevalent type of heart disease is caused by atherosclerosis, the thickening of the vessel wall and creation of atherosclerotic plaque. In this project, we will develop an imaging tool for the compre- hensive assessment of atherosclerotic plaque composition and vulnerability, with a clear pathway for translation into the clinical environment to enable the determination of the optimal treatment strategy in individual patients.