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: 10576857
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576857
• 关键词: Acceleration; Anti-Inflammatory Agents; Antiinflammatory Effect; Aorta; Architecture; Arterial Fatty Streak; Arteriogram; Atherosclerosis; Biological; Biology; Catheters; Cause of Death; Cessation of life; Clinical; Colchicine; Coronary; Coronary Arteriosclerosis; Coronary artery; Development; Diameter; 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 Selection; 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; coronary plaque; design; disability; ezetimibe; high risk; imaging approach; imaging modality; imaging system; implantation; improved; improved outcome; in vivo; in vivo evaluation; 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; structural imaging; 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.

摘要 此R01应用程序的目标是改进动脉粥样硬化和血管内的治疗 通过可翻译的血管内成像照亮支架的潜在病理生物学 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 近红外荧光血管内超声成像系统(NIRF-IVUS) 动脉。然后，我们将利用NIRF-IVUS来阐明炎症在评估和引导中的作用 动脉粥样硬化与支架再狭窄药物治疗策略。冠心病(CAD)是一种 这是世界范围内导致死亡和残疾的主要原因，通常需要冠状动脉支架治疗。生物学 炎症等分子过程会导致毁灭性的CAD和支架并发症，但在很大程度上 对于现代临床成像方法来说是不可见的。冠状动脉成像和量化的能力 炎症等分子过程将改善患者的风险分层，指导选择CAD 和支架药物疗法，并帮助简化0阶段的CAD和支架疗法的开发 /临床前至第四阶段/批准后阶段。 我们的实验室共同开发了新颖和创新的血管内成像系统，将高密度的 分辨率IVUS是冠状动脉内主要的结构成像方法，结合NIRF分子成像，a 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-IVUS检测高危斑块和 有并发症风险的支架置入，进一步指导个体化选择动脉药物治疗。这个 该提案的具体目标是：目标1：开发针对智能网而优化的下一代NIRF-IVUS v2.0系统 活体冠状动脉内成像，并在活体内测试猪冠状动脉支架炎症模型。目标2： 显示炎症的NIRF-IVUS措施推动动脉粥样硬化进展和动脉粥样硬化血栓形成 并预测对FDA批准的动脉粥样硬化剂Ezetimibe的反应。目标3：示范 NIRF-IVUS炎症指标可在体内驱动支架再狭窄，并可预测对 秋水仙碱，一种FDA批准的治疗方法，有可能减少再狭窄。 本研究的长期目标是为临床NIRF-IVUS提供翻译基础，以及 提供一种新的、个性化的医学方法，以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。这一知识的临床翻译可以 提供一种使用血管内NIRF-IVUS来改善冠心病患者预后的新范例。

项目成果

Accounting for blood attenuation in intravascular near-infrared fluorescence-ultrasound imaging using a fluorophore-coated guidewire.

• DOI: 10.1117/1.jbo.28.4.046001
• 发表时间: 2023-04
• 期刊: Journal of biomedical optics
• 影响因子: 3.5