NIRF-OFDI of Inflammation in Atheroma Progression and Stent Complications

描述(申请人提供)：冠状动脉疾病(CAD)是心脏病发作、死亡和残疾的全球主要原因，每年导致数十亿美元的医疗支出。临床上，一种广泛有效的冠心病介入治疗方法是使用冠状动脉金属支架的经皮冠状动脉介入治疗(PCI)。仅在美国，每年就有100多万个冠状动脉支架被放置。然而，两种并发症可能会限制冠状动脉支架的益处：再狭窄(疤痕形成)和血栓形成(凝血)。防止斑块恶化和支架并发症将消除每年数十万例侵入性导尿术、心脏病发作和死亡。从生物学上讲，炎症是所有 这些疾病包括：动脉粥样硬化、支架再狭窄和支架血栓形成。然而，炎症驱动斑块进展和支架置入术的损伤反应的体内机制仍然知之甚少。对体内炎症进行定量成像的能力，特别是使用可翻译的技术，可以为临床提供相关的、至关重要的新见解 这些障碍。为了解决这一未得到满足的需求，我们的实验室正在开发针对冠状动脉的血管内近红外荧光(NIRF)分子成像方法，以成像和量化动脉炎症和支架愈合。最近，我们开发了一种早期血管内NIRF-光频域成像(OFDI，Natural Medicine 2011；17：1680-4)系统，用于在动脉结构的背景下对分子信号进行定量成像。这项建议的目的是开发可翻译的血管内NIRF-OFDI分子微结构成像方法，以更好地了解斑块进展和支架并发症的机制。这项建议验证了中心假设，即整合的NIRF-OFDI将全面评估体内炎症在推动斑块进展、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，并最终减少冠心病和支架并发症的巨大负担。这项建议的具体目标是：具体目标1。设计下一代血管内NIRF-OFDI2.9F导管系统。明确目标2：确定斑块炎症如何调节动脉粥样硬化进展和支架再狭窄。明确目标3：确定斑块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)提供关于炎症在调节动脉粥样硬化进展、再狭窄和支架愈合不良中的作用的新的、有价值的病理生物学知识；(2)提供可翻译的炎症结构成像策略，从而最终改善冠心病患者和接受冠状动脉支架植入术的患者的预后，从而改变动脉粥样硬化和冠状动脉支架置入术领域。

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.