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 该R01应用的目的是改善动脉粥样硬化和血管内的治疗 通过通过可翻译的血管内成像来阐明其潜在病理生物学 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血管 针对人冠状动脉的近红外荧光内部超声（NIRF-IVUS）成像系统 动脉。然后，我们将利用Nirf-Ivus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 全球死亡和残疾的主要原因，通常需要冠状动脉支架进行治疗。生物 和分子过程，例如炎症驱动毁灭性的CAD和支架并发症，但在很大程度上是 与当代临床成像方法无关。图像和量化冠状动脉动脉的能力 分子过程（例如炎症）将改善患者风险分层，指导选择CAD 和支架药物疗法，并帮助简化第0阶段的CAD和支架治疗剂开发 /临床前IV/IV/后批准阶段。 我们的实验室共同开发了新颖和创新的血管内成像系统，结合了高度 分辨率IVU，是主要的冠状结构成像方法，具有NIRF分子成像，A 在快速临床翻译下，强大的新分子成像方法。在此应用程序中，我们将 大大提高了血管内NIRF-IVU的转化潜力，以检测高风险斑块和 支架有并发症的风险，并进一步指导个性化的动脉药物疗法选择。这 该提案的具体目的是：目标1：开发针对IN优化的下一代NIRF-IVUS v2.0系统 体内冠状动脉内成像，并在猪串行冠状动脉支架炎症模型中进行体内测试。目标2： 证明NIRF-IVU的炎症测量促进了动脉瘤进展和动脉粥样硬化 体内，并预测对FDA批准的动脉粥样硬化剂Ezetimibe的反应。目标3：演示 炎症的NIRF-IVU量度驱动体内的支架再狭窄，并预测了对 秋水仙碱是一种由FDA批准的疗法，可减少再狭窄。 这项研究的长期目标是为临床NIRF-IVU和 提供一种新的个性化医学方法来选择患者进行抗炎疗法以减少 斑块进展，动脉粥样硬化和支架并发症。这种知识的临床翻译可能 使用血管内NIRF-IVU提供新的范式，以改善CAD患者的预后。