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

项目总结： 易损斑块是急性冠脉综合征的主要致病因素。在早期阶段，脆弱的斑块 没有血流限制，因此在X射线血管成像中看不到。薄帽纤维瘤，被发现是 与斑块破裂相关的前驱病变的特点是纤维帽薄，有大的坏死性脂池， 和炎症。在R01HL125385的支持下，我们团队开发了一种血管内光声 (IVPA)体内检测载脂斑块的成像方式，同时测量脂质特异性 动脉壁中的成分及其深度，在9篇期刊文章和2本书的两章中总结。朝向 在人类患者中识别和量化载脂易损斑块的长期目标，我们 认识到目前基于压电式换能器的IVPA技术具有内在的局限性。首先， 血脂检测的灵敏度受到低频PA信号覆盖不足的限制；第二， 压电式换能器的带宽不足以提供足够的轴向分辨率来识别薄层 纤维帽(通常为&lt；65μm)；第三，压电换能器使测量最终尺寸变得困难 IVPA导管符合临床要求(直径1 mm)。为了解决这些限制，这一竞争对手 更新R01方案旨在开发一种新型的全光学IVUS/PA导管，并在体内验证该系统 临床相关的Ossabaw猪模型的动脉成像。组建了一个跨学科团队，以 实现这一目标。郑继新博士(波士顿大学派)是开发和应用的专家 新的无标签光学成像方法。Michael Sturek博士(印第安纳大学学院联合研究员 医学)是血管研究和动脉粥样硬化动物模型开发方面的专家。伊斯兰·A·博拉德博士 (印第安纳大学医学院顾问)是一位介入心脏病专家，他有20多年的 多模式血管内成像工具的临床研究经验；周启发博士(大学顾问 是超声波换能器方面的专家。曹迎春博士(波士顿研究科学家 大学)是光纤和导管开发方面的专家。我们将采取三个步骤来构建这一全光网络 IVUS/PA导管。在目标1中，我们将开发一种具有光学分辨率PA的双频IVPA/US导管 成像能力。在目标2中，我们将开发和验证一种全光学IVPA/US导管，具有高灵敏度和 高轴向分辨率。在目标3中，我们将通过活体冠状动脉成像来验证全光学IVUS/PA系统 在奥萨巴猪模型上。我们的血管内光纤超声产生和检测方法将 提供显著扩展的带宽，这不仅允许对低频功率放大器进行灵敏检测 此外，还克服了IVPA和IVUS成像长期以来空间分辨率不足的问题。

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.