NIRF-OFDI of Inflammation in Atheroma Progression and Stent Complications

动脉粥样硬化进展和支架并发症中炎症的 NIRF-OFDI

• 批准号: 8815887
• 负责人: Farouc Amin Jaffer
• 金额: $ 45.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-11-14 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8815887
• 关键词: Address; Area; Arterial Fatty Streak; Arteries; Arteriogram; Atherosclerosis; Automobile Driving; Catheterization; Catheters; Cessation of life; Cicatrix; Clinical; Coagulation Process; Coronary; Coronary Arteriosclerosis; Coronary artery; Deposition; Development; Disease; Engineering; Exhibits; Expenditure; Fibrin; Fluorescence; Goals; Healed; Healthcare; Histopathology; Human; Hyperplasia; Image; In Vitro; Inflammation; Inflammatory; Knowledge; Laboratories; Lesion; Life; Measurement; Medicine; Metals; Molecular; Myocardial Infarction; Myocardial Ischemia; Nature; Near-infrared optical imaging; Oryctolagus cuniculus; Outcome; Patients; Peptide Hydrolases; Performance; Pharmaceutical Preparations; Prevention; Publishing; Research; Risk; Role; Signal Transduction; Staging; Stents; Structure; System; Technology; Testing; Thrombosis; Translating; Ultrasonography; clinically relevant; computer studies; disability; effective therapy; healing; imaging system; improved; in vivo; insight; knowledge translation; molecular imaging; new technology; next generation; optical frequency domain imaging; percutaneous coronary intervention; prevent; prototype; public health relevance; response; response to injury; restenosis; sensor; stent thrombosis

DESCRIPTION (provided by applicant): Coronary artery disease (CAD) is a worldwide leading cause of heart attacks, death and disability, and leads to billions of dollars of healthcar expenditures each year. Clinically, a widely effective interventional treatment for CAD is percutaneous coronary intervention (PCI) using coronary metal stents. Over 1 million coronary stents are placed annually in the US alone. Yet, two complications can limit the benefit of coronary stents: restenosis (scarring), and thrombosis (clotting). Prevention of plaque progression and stent complications would eliminate hundreds of thousands of invasive catheterizations, heart attacks, and deaths each year. Biologically, inflammation underlies all of these diseases: atherosclerosis, stent restenosis, and stent thrombosis. Yet the in vivo mechanisms by which inflammation drives plaques progression and the injury response to stenting remains poorly understood. The ability to quantitatively image inflammation in vivo, especially with translatable technology, could provide clinically relevant, vital new insights into these disorders. To address this unmet need, our laboratory is developing coronary artery-targeted intravascular near-infrared fluorescence (NIRF) molecular imaging approaches to image and quantify arterial inflammation and stent healing. Most recently we have developed an early-stage intravascular NIRF-optical frequency domain imaging (OFDI, Nature Medicine 2011; 17:1680-4) system to quantitatively image molecular signals in the context of arterial structure. The objective of this Proposal is to develop translatable intravascular NIRF-OFDI molecular-microstructural imaging approaches to better understand mechanisms of plaque progression and stent complications. This Proposal tests the central hypothesis that integrated NIRF-OFDI will comprehensively assess the role of in vivo inflammation in driving plaque progression, stent restenosis, and stent thrombosis. Our long-term goal is to assess inflammatory mechanisms in human coronary arteries and to ultimately reduce the immense burden of CAD and stent complications. The Specific Aims of this proposal are: Specific Aim 1. To engineer a next-generation intravascular NIRF-OFDI 2.9F catheter system. Specific Aim 2. To determine how plaque inflammation modulates atheroma progression and stent restenosis. Specific Aim 3. To determine how plaque inflammation modulates stent healing and risk of stent thrombosis. This research will transform the field of atherosclerosis and coronary stenting by (1) providing new, valuable pathobiological knowledge about the role of inflammation in regulating atheroma progression, restenosis, and stent malhealing; and (2) provide translatable strategies for inflammation-structural imaging, to ultimately improve the outcomes of patients with CAD and those undergoing coronary stenting.

描述（由申请人提供）：冠状动脉疾病（CAD）是全球心脏病发作，死亡和残疾的主要原因，每年导致数十亿美元的医疗费用。在临床上，使用冠状化金属支架是经皮冠状动脉介入（PCI），对CAD进行了广泛有效的干预治疗。仅美国，每年将超过100万个冠状动脉支架放置在美国。然而，两个并发症可以限制冠状动脉支架的益处：再狭窄（疤痕）和血栓形成（凝结）。预防牙菌斑进展和支架并发症将消除每年数十万个侵入性导管，心脏病发作和死亡。 从生物学上讲，炎症是所有的基础 这些疾病：动脉粥样硬化，支架再狭窄和支架血栓形成。然而，炎症驱动斑块进展的体内机制和对支架支架的损伤反应仍然很少了解。在体内进行定量图像炎症的能力，尤其是使用可翻译技术的能力，可以为临床上相关的，重要的新见解 这些疾病。为了满足这种未满足的需求，我们的实验室正在开发冠状动脉动脉内血管内近红外荧光（NIRF）分子成像方法，以形象和量化动脉炎症和支架愈合。最近，我们开发了一种早期的血管内NIRF光学频率域成像（OFDI，Nature Medicine 2011; 17：1680-4）在动脉结构的背景下定量图像分子信号。 该建议的目的是开发可翻译的血管内NIRF-OFDI分子微观结构成像方法，以更好地了解斑块进展和支架并发症的机制。该提案检验了一个中心假设，即综合的NIRF-OFDI将全面评估体内炎症在驱动斑块进展，支架再狭窄和支架血栓形成中的作用。我们的长期目标是评估人类冠状动脉的炎症机制，并最终减轻CAD和支架并发症的巨大负担。该提案的具体目的是：具体目的1。设计下一代血管内NIRF-OFDI 2.9F导管系统。具体目的2。确定牙菌斑炎症如何调节动脉粥样硬化的进展和支架再狭窄。具体目的3。确定牙菌斑炎症如何调节支架愈合和支架血栓形成的风险。这项研究将通过（1）提供有关炎症在调节动脉粥样硬化进展，再狭窄和支架不良症中的作用的新的，有价值的病理学知识，从而改变动脉粥样硬化和冠状动脉支架的领域； （2）为炎症结构成像提供了可翻译的策略，以最终改善CAD患者的结局和患有冠状动脉支架的患者的结果。