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

项目摘要/摘要 冠心病的临床处理与急性冠脉综合征的预防 (ACS)需要了解潜在的动脉粥样硬化斑块病理生物学。电流血管内 独立的成像技术在评估导致斑块进展的过程方面的能力有限 以及斑块结构的突然变化(如破裂或侵蚀)有利于人类的急性冠脉综合征。混血儿 血管内成像系统为更全面地评估斑块病理生物学提供了前提。 患者和急切需要。我们的目标是通过开发一种血管内支架来满足这种需求 一种可同时评估斑块生化成分和斑块变化的成像方法 形态学与患者的关键病理生物学过程相关。我们建议提前一年 结合两种互补的无标记光学技术的血管内成像系统，具体地说， 荧光寿命成像(FLIM)和偏振敏感光学相干层析成像(PSOCT) 一种适用于经皮冠状动脉成像(PCI)的创新双峰成像导管。这是一种双重模式 方法应该1)深入了解具有关键作用的生化-形态特征之间的相互作用 在斑块进展、失稳和/或重塑中的作用和/或2)能够立即显示这些信息 以接近实时的可视格式，可用于指导当时的冠状动脉病变的个性化管理 心导管插入术。建议的技术将能够安全和快速地进行联合注册 测量(1)多个光谱发射带中的时间分辨荧光衰减，以及(2)偏振- 一次回调即可解析光学层析数据。为了实现我们的目标，我们将首先构建一个薄膜-PSOCT 包括自由形状反射光学的导管系统，为薄膜和 PSOCT(目标1)。第二，展示Flim-PSOCT在快速和同步/协同方面的性能 评估与不同形态特征相关的关键生化特征，我们将使用 建议的混合系统成像人类冠状动脉样本(体外)，并有组织病理学证实(AIM2)。 最后，我们将在患者(首例人类)中应用该系统来评估心导管置入术中的斑块。 并确定临床可行性(目标3)。这项研究的成功完成将证明这项临床 冠状动脉内FLIM-PSOCT用于评估可能导致急性冠脉综合征的关键斑块特征的可行性和实用性。 如果能够可靠地检测到这些特征，接受经皮冠状动脉介入治疗的患者可能会受益于个性化 这些斑块的治疗和改善的结果。

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.