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）：在导致其毁灭性的心肌梗死和中风并发症之前，迫切需要使用新的成像方法来识别和指导高危动脉粥样硬化斑块的治疗。虽然成像技术在照明斑块体积和牙菌斑结构方面取得了进展，但它们并未常规地可视化斑块生物学的各个方面，例如炎症，这是斑块并发症的关键决定因素。 动脉粥样硬化中分子和细胞细节的成像提供了一种变革性的方法，可改善生物学诊断，风险分层和高危斑块的治疗。此外，动脉粥样硬化的分子成像可以鉴定出有利改变牙菌斑生物学（例如抗炎）的新药物疗法，并有可能简化药物发育并有效地将新疗法带入诊所。然而，目前，现有的分子成像方法无法常规地可视化人类冠状动脉中的高风险斑块。 该赠款提案的长期目标是开发新的人类冠状动脉动脉内血管内近红外荧光（NIRF）分子成像策略，以鉴定负责心肌梗塞的动脉粥样硬化斑块。最近，一种一维手动回调性血管内NIRF传感导管确定了成像斑块炎症通过冠状动脉大小的血管中的可行性。该提案现在旨在开发下一代内血管内NIRF导管，能够在体内人类冠状动脉大小的动脉中具有真正的两维NIRF成像。特定的目标1将设计，构建和验证旋转和自动回调的NIRF导管，以使兔主动脉症中的动脉瘤炎症启用360度和纵向2D容器壁成像，这是对现有限量的限量ARC ARCSPECTROSCOPIC NIRF CATERES的进步。具体目标2将利用经过验证的NIRF旋转导管评估实验性动脉粥样硬化中的抗炎症（他汀类药物）作用，从而扩展了体内成像armammentarium，以评估治疗剂对血管疾病的功效。具体目标3研究了由FDA批准的诊断成像剂吲哚氰氨酸绿色的能力，可作为动脉粥样硬化斑块的炎症针对炎症的炎症性血管内NIRF成像剂。特定的目标4测试了NIRF导管直接在体内实验性冠状动脉中进行分子成像的能力，目的是加速导管转化为临床领域。该提案建立在研究人员实验室中既定的大型动物导管成像努力的基础上，并从多学科团队中建立了工程，成像和生物学专业知识。 公共卫生相关性：迫切需要采用新的成像方法来识别高危动脉粥样硬化斑块在引起心脏病发作之前。该研究项目旨在开发新的荧光导管，并采用用于人类冠状动脉大小动脉中高风险斑块的成像的方法。该项目的结果可以使临床荧光成像策略的发展以减少心脏病发作。