Morphological and Molecular Imaging System for in vivo Atherosclerosis Research

描述（由申请人提供）：动脉粥样硬化是美国发病率和死亡率的主要原因，其特征是一种全身性进行性疾病过程，其中动脉壁通过炎症、氧化应激和血脂异常增厚。这一过程导致斑块的形成和血管腔内的血流受限。动脉斑块的突然破裂导致血栓形成和血管突然闭塞，最终导致心肌梗死、中风或肢体损伤。动脉粥样硬化的全身或局部治疗的未来发展可能取决于对斑块发展的更详细的了解。提高对斑块发展的理解需要在体内监测斑块形成和/或对治疗反应的形态学、生化和功能/分子变化。不幸的是，目前没有影像学（非侵入性和血管内）可以提供这种水平的斑块特征。我们建议开发一种新的成像技术，通过将光学相干断层扫描（OCT）与内源性和外源性荧光寿命成像（FLIM）相结合，实现斑块形态、生化成分和分子活性的高速体内血管内成像。血管内OCT提供动脉粥样硬化斑块的高分辨率血管内成像。与稳态荧光相比，FLIM已被证明远不容易受到体内成像特有的伪影的影响。内源性斑块荧光成像可以量化斑块的生化含量。外源性荧光标签标记多个分子靶标的FLIM成像将允许监测斑块分子活性。为了发展和验证这种新的血管内成像模式，提出了以下三个具体目标。目的1：将OCT与内源性FLIM成像相结合，对不同类型的动脉粥样硬化斑块进行无损识别。目的2：设计并构建一种高速光学成像系统，包括双模光纤导管，适用于动脉粥样硬化斑块的体内血管内同步共登记OCT和内源性/外源性FLIM成像。目的3：量化OCT/FLIM血管内成像系统监测斑块形态、生化组成和体内分子活性的能力。我们相信，由此产生的血管内成像技术将有助于全面了解斑块的形成，并可能最终有助于促进动脉粥样硬化治疗的发展。

DESCRIPTION (provided by applicant): Atherosclerosis is the leading cause of morbidity and mortality in the United States and is characterized as a systemic, progressive disease process in which the arterial wall thickens through a process of inflammation, oxidative stress, and dyslipidemia. This process leads to plaque formation and flow limitation in the vessel lumen. The sudden rupture of this arterial plaques lead to thrombosis and sudden occlusion of the vessel and ultimately, in myocardial infarction, stroke, or limb injury. Future development of systemic or localized therapies for atherosclerosis will likely depend upon a more detailed understanding of plaque development. Improving the understanding of plaque development will require in-vivo monitoring of morphological, biochemical and functional/molecular changes accompanying plaque formation and/or response to treatments. Unfortunately, there is no current imaging modality (neither non-invasive nor intravascular) that can provide such level of plaque characterization. We propose to develop a novel imaging technology that will enable high-speed in vivo intravascular imaging of plaque morphology, biochemical composition and molecular activity, by combining optical coherence tomography (OCT) with endogenous and exogenous fluorescence lifetime imaging (FLIM). Intravascular OCT offers high-resolution intravascular imaging of atherosclerotic plaque. FLIM has been shown to be far less susceptible to artifacts endemic to in vivo imaging than steady-state fluorescence. FLIM imaging of endogenous plaque fluorescence allows quantifying plaque biochemical content. FLIM imaging of exogenous fluorescent tags labeling multiple molecular targets will allow monitoring plaque molecular activity. To develop and validate this novel intravascular imaging modality, the following three specific aims are proposed. Aim 1: To integrate OCT with endogenous FLIM imaging for non-destructive identification of the different types of atherosclerotic plaques. Aim 2: To design and build a high-speed optical imaging system, including a dual-mode fiber catheter, suitable for in vivo intravascular simultaneous and coregistered OCT and endogenous/exogenous FLIM imaging of atherosclerotic plaques. Aim 3: To quantify the capacity of the OCT/FLIM intravascular imaging system to monitor over time plaque morphology, biochemical composition and molecular activity in-vivo. We believe that the resulting intravascular imaging technology will enable comprehensive understanding of plaque development and may ultimately help facilitate the development of a cure for atherosclerosis.