Dual-modality FLIm and PSOCT for intravascular imaging of plaque in patients

PROJECT SUMMARY/ABSTRACT The clinical management of coronary artery disease (CAD) and the prevention of acute coronary syndromes (ACS) require knowledge of the underlying atherosclerotic plaque pathobiology. Current intravascular standalone imaging techniques are limited in their ability to evaluate processes that lead to plaque progression and sudden changes in plaque structure (e.g. rupture or erosion) conducive to ACS in humans. Hybrid intravascular imaging systems hold premises for a more comprehensive evaluation of plaque pathobiology in patients and are urgently needed. Our goal is to address this need through the development of an intravascular imaging approach capable of simultaneous assessment of changes in plaque biochemical composition and morphology associated with critical pathobiological processes in patients. We propose to advance an intravascular imaging system combining two complementary label-free optical techniques, specifically, Fluorescence Lifetime Imaging (FLIm) and Polarization Sensitive Optical Coherent Tomography (PSOCT) via an innovative bimodal imaging catheter suitable for percutaneous coronary imaging (PCI). This dual-modality approach should 1) yield great insight into the interplay of biochemical-morphological features that have a key role in plaque progression, destabilization and/or remodeling and 2) enable immediate display this information in near real-time, in a visual format useful for guiding personalized management of coronary lesions at the time of cardiac catheterization. The proposed technique will be able to perform safe and rapid co-registered measurement of (1) time-resolved fluorescence decays in multiple spectral emission bands, and (2) polarization- resolved optical tomographic data in a single pullback. To achieve our goal, we will first construct a FLIm-PSOCT catheter system including a freeform reflective optic providing optimized optical performance for both FLIm and PSOCT (Aim 1). Second, to demonstrate FLIm-PSOCT’s performance for fast and simultaneous/synergetic assessment of critical biochemical features associated with distinct morphological features, we will use the proposed hybrid system to image human coronary samples (ex vivo), with histopathology corroboration (Aim2). Finally, we will deploy this system in patients (first-in-human) to evaluate plaques during cardiac catheterization and determine clinical feasibility (Aim 3). The successful completion of this study will demonstrate the clinical feasibility and utility of intracoronary FLIm-PSOCT for assessment of critical plaque features likely to cause ACS. If such features can be reliably detected, the patients undergoing PCI procedures may benefit from personalized treatment of these plaques and improved outcome.