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

项目摘要： 易损斑块是急性冠状动脉综合征的主要原因。在早期阶段，易损斑块 不限制血流，因此在X射线血管造影中不可见。薄帽纤维粥样硬化，这被发现是 与斑块破裂相关的前驱病变的特征在于薄的纤维帽，大的坏死脂质池， 和炎症。在R 01 HL 125385的支持下，我们的团队开发了一种血管内光声 （IVPA）成像模式，其用于体内检测载脂斑块，其同时测量脂质特异性 成分及其在动脉壁中的深度，在9篇期刊文章和2本书的章节中进行了总结。朝向 长期目标是鉴定和量化人类患者中富含脂质的易损斑块，我们 认识到当前基于压电换能器的IVPA技术具有固有的局限性。一是 脂质检测的灵敏度受到低频PA信号覆盖不足的限制;其次， 压电换能器的带宽不足以提供足够的轴向分辨率来识别薄的 纤维帽（通常< 65 μm）;第三，压电换能器使最终尺寸的 IVPA导管满足临床要求（直径< 1 mm）。为了解决这些局限性， 更新R 01提案旨在开发一种新型全光学IVUS/PA导管，并通过体内试验验证该系统 在临床相关的Ossabaw猪模型中的动脉成像。组建了一个跨学科的团队， 实现这一目标。Ji-Xin Cheng博士（PI，波士顿大学）是开发和应用 新颖的无标记光学成像方法。Michael Sturek博士（合作研究者，印第安纳州大学医学院） 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。伊斯兰博士波拉德 （印第安纳州大学医学院顾问）是一名介入心脏病专家， 多模式血管内成像工具的临床研究经验;周启发博士（顾问，大学 是超声波传感器的专家。曹迎春博士（研究科学家，波士顿 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建立这个全光学 IVUS/PA导管。目标一：研制具有光学分辨率PA的双频IVPA/US导管 成像能力。在目标2中，我们将开发和验证具有高灵敏度的全光学IVPA/US导管， 高轴向分辨率。在目标3中，我们将通过体内冠状动脉内成像来验证全光学IVUS/PA系统 奥萨博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，这不仅允许灵敏地检测低频PA 信号，而且还克服了IVPA和IVUS成像两者的长期存在的空间分辨率不足。

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.