Intravascular Fluorescence Molecular Imaging of Inflammation in Atherosclerosis

动脉粥样硬化炎症的血管内荧光分子成像

• 批准号: 8121532
• 负责人: Farouc Amin Jaffer
• 金额: $ 43.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8121532
• 关键词: Angiography; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Applications Grants; Arterial Fatty Streak; Arteries; Atherosclerosis; Biological; Biology; Blood; Calcium Chloride; Caliber; Cathepsins; Catheters; Clinic; Clinical; Collaborations; Collagen; Computer software; Confocal Microscopy; Control Animal; Coronary; Coronary artery; Custom; Detection; Development; Diagnosis; Diagnostic Imaging; Dose; Engineering; FDA approved; Family suidae; Fiber; Fibrin; Fluorescence; Fluorescence Microscopy; Fluorescent Dyes; Foundations; Fresh Frozen Plasmas; Goals; Human; Image; Imaging technology; Immunohistochemistry; Implant; In Vitro; Incubated; Indocyanine Green; Inflammation; Inflammatory; Injection of therapeutic agent; Laboratories; Lasers; Lead; Lipids; Manuals; Measures; Myocardial Infarction; Noise; Oryctolagus cuniculus; Peptide Hydrolases; Performance; Pharmacotherapy; Research Personnel; Research Project Grants; Resolution; Risk; Signal Transduction; Source; Staining method; Stains; Stents; Stratification; Stroke; Structure; System; Testing; Thrombin; Thrombus; Time; Translations; Treatment Efficacy; Ultrasonography; Vascular Diseases; Writing; base; design; design and construction; dosage; drug development; fluorescence imaging; high risk; image reconstruction; imaging modality; improved; in vivo; inflammatory marker; injured; molecular imaging; molecular/cellular imaging; multidisciplinary; nanoparticle; next generation; novel; public health relevance; research study; response; success; two-dimensional

DESCRIPTION (provided by applicant): New imaging methods are urgently needed to identify and to guide treatment of high-risk atherosclerotic plaques before lead to their devastating complications of myocardial infarction and stroke. While imaging technologies have made progress in illuminating plaque volume and plaque structure, they do not routinely visualize aspects of plaque biology such as inflammation, a key determinant of plaque complications. Imaging of molecular and cellular detail in atherosclerosis offers a transformative approach to improve the biological diagnosis, risk stratification, and treatment of high-risk plaques. In addition, molecular imaging of atherosclerosis can identify new pharmacotherapies that favorably alter plaque biology (e.g. anti-inflammatory), with the potential to streamline drug development and to efficiently bring new therapies into the clinic. At present however, existing molecular imaging approaches are unable to routinely visualize high-risk plaques in human coronary arteries. The long-term objective of this grant proposal is to develop new human coronary artery-targeted intravascular near-infrared fluorescence (NIRF) molecular imaging strategies to identify atherosclerotic plaques responsible for myocardial infarction. Recently, a one-dimensional, manual pullback intravascular NIRF sensing catheter established the feasibility of imaging plaque inflammation through blood in coronary-sized vessels. The Proposal now aims to develop a next-generation intravascular NIRF catheter capable of true two- dimensional NIRF imaging in human coronary-sized arteries in vivo. Specific Aim 1 will design, construct, and validate a rotational and automated pullback NIRF catheter to enable 360-degree and longitudinal 2D vessel wall imaging of atheroma inflammation in rabbit aortic vessels, an advance over existing limited-arc spectroscopic NIRF catheters. Specific Aim 2 will utilize the validated NIRF rotational catheter to assess anti- inflammatory (statin) effects in experimental atherosclerosis, extending the in vivo imaging armamentarium to assess the efficacy of therapeutics for vascular disease. Specific Aim 3 investigates the ability of indocyanine green, an FDA-approved diagnostic imaging agent, to serve as an inflammation-targeted intravascular NIRF imaging agent for atherosclerotic plaques. Specific Aim 4 tests the NIRF catheter's ability to perform molecular imaging directly in experimental coronary arteries in vivo, with the goal of accelerating catheter translation into the clinical arena. The Proposal builds on established large animal catheter-based imaging efforts in the Investigator's laboratory and leverages established engineering, imaging, and biological expertise from a multidisciplinary team. PUBLIC HEALTH RELEVANCE: New imaging methods are urgently needed to identify high-risk atherosclerotic plaques before they cause heart attacks. This research project is directed at developing new fluorescence catheters and approaches for imaging of high-risk plaques in human coronary-sized arteries. The results from this project could enable the development of clinical fluorescence imaging strategies to reduce heart attacks.

描述（由申请人提供）：迫切需要新的成像方法来识别和指导高风险动脉粥样硬化斑块的治疗，以免导致心肌梗塞和中风等破坏性并发症。虽然成像技术在阐明斑块体积和斑块结构方面取得了进展，但它们通常无法可视化斑块生物学的各个方面，例如炎症，而炎症是斑块并发症的关键决定因素。 动脉粥样硬化的分子和细胞细节成像为改善高风险斑块的生物学诊断、风险分层和治疗提供了一种变革性方法。此外，动脉粥样硬化的分子成像可以识别有利于改变斑块生物学（例如抗炎）的新药物疗法，有可能简化药物开发并有效地将新疗法引入临床。然而，目前现有的分子成像方法无法常规地观察人类冠状动脉中的高风险斑块。 该拨款提案的长期目标是开发新的人类冠状动脉靶向血管内近红外荧光（NIRF）分子成像策略，以识别导致心肌梗塞的动脉粥样硬化斑块。最近，一维手动回拉血管内 NIRF 传感导管确立了通过冠状动脉大小的血管中的血液对斑块炎症进行成像的可行性。该提案现在的目标是开发下一代血管内 NIRF 导管，能够在体内对人体冠状动脉大小的动脉进行真正的二维 NIRF 成像。具体目标 1 将设计、构建和验证旋转和自动回拉 NIRF 导管，以实现兔主动脉血管粥样斑块炎症的 360 度纵向 2D 血管壁成像，这是对现有有限弧光谱 NIRF 导管的进步。具体目标 2 将利用经过验证的 NIRF 旋转导管来评估实验性动脉粥样硬化中的抗炎（他汀类药物）效果，扩展体内成像设备以评估血管疾病治疗的功效。具体目标 3 研究了吲哚菁绿（FDA 批准的一种诊断成像剂）作为针对动脉粥样硬化斑块的炎症靶向血管内 NIRF 成像剂的能力。具体目标 4 测试 NIRF 导管直接在体内实验冠状动脉中进行分子成像的能力，目标是加速导管转化为临床领域。该提案建立在研究者实验室中已建立的基于大型动物导管的成像工作的基础上，并利用了多学科团队已建立的工程、成像和生物专业知识。 公共卫生相关性：迫切需要新的成像方法来在高风险动脉粥样硬化斑块引起心脏病发作之前识别它们。该研究项目旨在开发新的荧光导管和方法，用于对人类冠状动脉大小的高风险斑块进行成像。该项目的结果可以促进临床荧光成像策略的开发，以减少心脏病发作。