Intravascular NIRF-IVUS imaging of inflammation-guided arterial therapy

炎症引导动脉治疗的血管内 NIRF-IVUS 成像

• 批准号: 10364770
• 负责人: Farouc Amin Jaffer
• 金额: $ 49.81万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-17 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364770
• 关键词: Anti-Inflammatory Agents; Antiinflammatory Effect; Architecture; Arterial Fatty Streak; Arteriogram; Atherosclerosis; Biological; Biology; Caliber; Catheters; Cause of Death; Cessation of life; Clinical; Colchicine; Coronary; Coronary Arteriosclerosis; Coronary artery; Development; Dose; Elements; Engineering; Event; Exhibits; FDA approved; Family suidae; Fluorescence; Foundations; Generations; Goals; Guidelines; Heart; Human; Image; Individual Differences; Inflammation; Inflammatory Response; Knowledge; Laboratories; Light; Lipids; Measures; Medicine; Metals; Methods; Modeling; Molecular; Morbidity - disease rate; Myocardial Infarction; National Heart, Lung, and Blood Institute; Oryctolagus cuniculus; Outcome; Patient risk; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Process; Program Development; Property; Randomized; Research; Research Priority; Resolution; Risk; Role; Speed; Stents; Structure; System; Testing; Therapeutic; Time; Translations; Ultrasonography; atherothrombosis; clinical imaging; clinical translation; clinically translatable; coronary plaque; design; disability; ezetimibe; high risk; imaging approach; imaging modality; imaging system; implantation; improved; improved outcome; in vivo; innovation; knowledge translation; miniaturize; molecular imaging; mortality; next generation; novel; novel strategies; novel therapeutics; personalized medicine; point of care; pre-clinical; precision medicine; predicting response; prototype; response; restenosis; risk stratification; sound; sudden cardiac death; therapeutic development; therapeutic target; thrombogenesis; translational potential; ultrasound

ABSTRACT The goal of this R01 application is to improve the treatment of atherosclerosis and endovascular stenting by illuminating their underlying pathobiology through translatable intravascular imaging of arterial inflammation and structure. To achieve this goal, we will engineer a next-generation intravascular near-infrared fluorescence-intravascular ultrasound (NIRF-IVUS) imaging system targeted to human coronary arteries. We will then harness NIRF-IVUS to elucidate the role of inflammation in assessing and guiding atherosclerosis and stent restenosis pharmacotherapeutic strategies. Coronary artery disease (CAD) is a worldwide leading cause of death and disability, and often requires coronary stenting for treatment. Biological and molecular processes such as inflammation drive devastating CAD and stent complications, but are largely invisible to contemporary clinical imaging methods. The ability to image and quantify coronary arterial molecular processes such as inflammation would improve patient risk stratification, guide the selection CAD and stent pharmacotherapies, and help streamline CAD and stent therapeutics development from phase 0 /preclinical to phase IV/post-approval stages. Our laboratory has co-developed novel and innovative intravascular imaging systems that combine high- resolution IVUS, the dominant intracoronary structural imaging method, with NIRF molecular imaging, a powerful new molecular imaging approach under rapid clinical translation. In this application, we will substantially improve the translational potential of intravascular NIRF-IVUS to detect high-risk plaques and stents at risk of complications, and further guide the personalized selection of arterial pharmacotherapy. The Specific Aims of this proposal are: Aim 1: Develop a next generation NIRF-IVUS v2.0 system optimized for in vivo intracoronary imaging, and test in vivo in a swine serial coronary stent inflammation model. Aim 2: Demonstrate that NIRF-IVUS measures of inflammation drive atheroma progression and atherothrombosis in vivo, and predict the response to ezetimibe, an FDA-approved atherosclerosis agent. Aim 3: Demonstrate that NIRF-IVUS measures of inflammation drive stent restenosis in vivo, and predict the response to colchicine, an FDA-approved therapy with the potential to reduce restenosis. The long-term objectives of this research are to provide a translational foundation for clinical NIRF-IVUS, and to provide a new, personalized medicine approach to select patients for anti-inflammatory therapy to reduce plaque progression, atherothrombosis, and stent complications. Clinical translation of this knowledge may provide a new paradigm using intravascular NIRF-IVUS to improve outcomes in patients with CAD.

抽象的 R01应用的目标是改善动脉粥样硬化和血管内治疗的治疗 通过可翻译的血管内成像阐明支架置入术的潜在病理学 动脉炎症和结构。为了实现这一目标，我们将设计下一代血管内 针对人体冠状动脉的近红外荧光血管内超声（NIRF-IVUS）成像系统 动脉。然后，我们将利用 NIRF-IVUS 来阐明炎症在评估和指导中的作用 动脉粥样硬化和支架再狭窄药物治疗策略。冠状动脉疾病（CAD）是一种 是世界范围内死亡和残疾的主要原因，通常需要冠状动脉支架植入术进行治疗。生物 炎症等分子过程会导致毁灭性的 CAD 和支架并发症，但很大程度上是 现代临床成像方法不可见。冠状动脉成像和量化的能力 炎症等分子过程将改善患者风险分层，指导选择 CAD 和支架药物疗法，并帮助简化 CAD 和支架疗法从 0 阶段的开发 /临床前到第四阶段/批准后阶段。 我们的实验室共同开发了新颖且创新的血管内成像系统，该系统结合了高 分辨率 IVUS，主要的冠状动脉内结构成像方法，具有 NIRF 分子成像， 快速临床转化的强大的新分子成像方法。在这个应用程序中，我们将 显着提高血管内 NIRF-IVUS 检测高风险斑块的转化潜力 支架的并发症风险，并进一步指导动脉药物治疗的个性化选择。这 该提案的具体目标是： 目标 1：开发针对 in 优化的下一代 NIRF-IVUS v2.0 系统 体内冠状动脉成像，并在猪连续冠状动脉支架炎症模型中进行体内测试。目标 2： 证明 NIRF-IVUS 炎症测量可促进动脉粥样硬化进展和动脉粥样硬化血栓形成 体内，并预测对依折麦布（FDA 批准的动脉粥样硬化药物）的反应。目标 3：展示 NIRF-IVUS 测量炎症驱动体内支架再狭窄，并预测对炎症反应的反应 秋水仙碱，FDA 批准的一种疗法，具有减少再狭窄的潜力。 这项研究的长期目标是为临床 NIRF-IVUS 提供转化基础，以及 提供一种新的个性化医疗方法来选择患者进行抗炎治疗，以减少 斑块进展、动脉粥样硬化血栓形成和支架并发症。这些知识的临床转化可能 提供了一种使用血管内 NIRF-IVUS 来改善 CAD 患者预后的新范例。