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

项目概要/摘要 冠状动脉疾病的临床处理和急性冠状动脉综合征的预防 (ACS)需要了解动脉粥样硬化斑块的病理学基础。当前血管内 独立的成像技术在评估导致斑块进展的过程的能力方面是有限的 以及斑块结构的突然变化（例如破裂或侵蚀），这有助于人类的ACS。混合 血管内成像系统为更全面地评价斑块病理生物学提供了前提， 患者，急需。我们的目标是通过开发血管内 能够同时评估斑块生化组成变化的成像方法， 形态学与患者的关键病理生物学过程相关。我们建议提出一项 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， 荧光寿命成像（FLIm）和偏振敏感光学相干断层扫描（PSOCT）， 一种适用于经皮冠状动脉成像（PCI）的创新型双峰成像导管。这种双重模式 这种方法应该：1）深入了解生物化学形态特征的相互作用，这些特征具有关键的 在斑块进展、不稳定和/或重塑中的作用，以及2）能够立即显示该信息 以接近实时的方式，以可视的形式，用于指导当时的冠状动脉病变的个性化管理， 心脏导管插入术所提出的技术将能够执行安全和快速的共注册 测量（1）多个光谱发射带中的时间分辨荧光衰减，和（2）偏振- 在单次回撤中解析光学层析成像数据。为了实现我们的目标，我们将首先构建FLIm-PSOCT 一种导管系统，其包括为FLIm和FLIm两者提供优化的光学性能的自由形式反射光学器件， PSOCT（目标1）。其次，为了证明FLIm-PSOCT的快速和同步/协同性能， 评估与不同形态学特征相关的关键生化特征，我们将使用 提出的混合系统，以成像人类冠状动脉样本（离体），与组织病理学确证（Aim 2）。 最后，我们将在患者中部署该系统（首次在人体中），以评估心导管插入术期间的斑块 并确定临床可行性（目标3）。本研究的成功完成将证明临床 冠状动脉内FLIm-PSOCT评估可能导致ACS的关键斑块特征的可行性和实用性。 如果可以可靠地检测到这些特征，则经历PCI手术的患者可以从个性化治疗中受益。 治疗这些斑块并改善结果。

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.