Sensing Vulnerable Plaque in vivo by an All-optical Intravascular Ultrasound and Photoacoustic Catheter

项目总结:

Project Summary: Vulnerable plaques are the main contributor to acute coronary syndrome. In early stages, vulnerable plaques are not blood flow limiting, thus not visible in X-ray angiography. Thin cap fibroatheroma, which is found to be the precursor lesion associated with plaque rupture, is featured by a thin fibrous cap, a large necrotic lipid pool, and inflammation. Under the support of R01HL125385, our team developed an intravascular photoacoustic (IVPA) imaging modality for in vivo detection of lipid-laden plaques, which simultaneously measures lipid-specific components and their depth in an artery wall, summarized in 9 journal articles and 2 book chapters. Towards the long-term goal of identification and quantification of lipid-laden vulnerable plaque in human patients, we recognize that current piezoelectric-transducer-based IVPA technology has intrinsic limitations. First, the sensitivity for lipid detection is limited by the insufficient coverage of the low-frequency PA signal; Second, the bandwidth of piezoelectric transducer is not large enough to provide sufficient axial resolution to identify the thin fibrous cap (typically < 65 μm); Third, the piezoelectric transducer makes it difficult for the eventual size of an IVPA catheter to meet the clinical requirement (< 1 mm in diameter). To address the limitations, this competitive renewal R01 proposal aims to develop a novel all-optical IVUS/PA catheter and validate the system by in vivo imaging of arteries in a clinically relevant Ossabaw swine model. An interdisciplinary team is assembled to achieve this objective. Dr. Ji-Xin Cheng (PI, Boston University) is an expert in development and applications of novel label-free optical imaging methods. Dr. Michael Sturek (co-investigator, Indiana University School of Medicine) is an expert in vascular research and atherosclerotic animal model development. Dr. Islam A. Bolad (consultant, Indiana University School of Medicine) is an interventional cardiologist who has over 20 years of experience on clinical research with multimodal intravascular imaging tools; Dr. Qifa Zhou (consultant, University of Southern California) is an expert of ultrasound transducers. Dr. Yingchun Cao (Research Scientist, Boston University) is an expert on fiber optics and catheter development. We will take three steps to build this all-optical IVUS/PA catheter. In Aim 1, we will develop a dual-frequency IVPA/US catheter with optical-resolution PA imaging capacity. In Aim 2, we will develop and validate an all-optical IVPA/US catheter with high sensitivity and high axial resolution. In Aim 3, we will validate the all-optical IVUS/PA system by in vivo intracoronary imaging on an Ossabaw swine model. Our intravascular fiber-optic ultrasound generation and detection approach will provide significantly extended bandwidth, which not only allows sensitive detection of the low frequency PA signal, but also overcomes the long-standing insufficient spatial resolution of both IVPA and IVUS imaging.