A Novel Intravascular CRI-PAT Imaging System to Characterize Vulnerable Plaque

用于表征易损斑块的新型血管内 CRI-PAT 成像系统

• 批准号: 9096884
• 负责人: Raiyan Tripti Zaman
• 金额: $ 16.12万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096884
• 关键词: Accounting; Address; Advisory Committees; Angiography; Animals; Aorta; Arterial Fatty Streak; Atherosclerosis; Autopsy; Autoradiography; Beta Carotene; Biology; Biomedical Engineering; Cardiovascular system; Career Mobility; Carotene; Carotid Arteries; Carotid Artery Plaques; Catheters; Cause of Death; Cessation of life; Characteristics; Cholesterol; Clinical; Collagen; Copper; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Databases; Detection; Developed Countries; Development; Diagnosis; Disease; Elastin; Electrical Engineering; Event; FDA approved; Family suidae; Fatty Acids; Fiber Optics; Future; Goals; Gold; Histology; Human; Image; Imaging Device; Imaging technology; Immunohistochemistry; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Laboratories; Lesion; Lipids; Location; Malignant Neoplasms; Maps; Medicine; Mentors; Mentorship; Methods; Modality; Modeling; Molecular Probes; Motion; Mus; Myocardial Infarction; Myocardium; Oryctolagus cuniculus; Phase; Radiation Oncology; Radiation Physics; Radio; Radioisotopes; Radionuclide Imaging; Real-Time Systems; Research; Research Personnel; Research Project Grants; Research Proposals; Resolution; Rupture; Safety; Signal Transduction; Societies; Specimen; Structure; System; Techniques; Testing; Thick; Thrombosis; Thrombus; Time; Tissues; Training; United States; Universities; Validation; Work; World Health Organization; acute coronary syndrome; base; calcification; cancer imaging; cardiovascular imaging; cardiovascular visualization; career; career development; glucose uptake; image reconstruction; imaging modality; imaging system; improved; in vivo; information gathering; lens; luminescence; macrophage; medical schools; meetings; miniaturize; molecular imaging; molecular marker; novel; optical imaging; plaque lesion; prevent; professor; programs; quantitative imaging; research study; sudden cardiac death; tomography; uptake; Accounting; Address; Advisory Committees; Angiography; Animals; Aorta; Arterial Fatty Streak; Atherosclerosis; Autopsy; Autoradiography; Beta Carotene; Biology; Biomedical Engineering; Cardiovascular system; Career Mobility; Carotene; Carotid Arteries; Carotid Artery Plaques; Catheters; Cause of Death; Cessation of life; Characteristics; Cholesterol; Clinical; Collagen; Copper; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Databases; Detection; Developed Countries; Development; Diagnosis; Disease; Elastin; Electrical Engineering; Event; FDA approved; Family suidae; Fatty Acids; Fiber Optics; Future; Goals; Gold; Histology; Human; Image; Imaging Device; Imaging technology; Immunohistochemistry; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Laboratories; Lesion; Lipids; Location; Malignant Neoplasms; Maps; Medicine; Mentors; Mentorship; Methods; Modality; Modeling; Molecular Probes; Motion; Mus; Myocardial Infarction; Myocardium; Oryctolagus cuniculus; Phase; Radiation Oncology; Radiation Physics; Radio; Radioisotopes; Radionuclide Imaging; Real-Time Systems; Research; Research Personnel; Research Project Grants; Research Proposals; Resolution; Rupture; Safety; Signal Transduction; Societies; Specimen; Structure; System; Techniques; Testing; Thick; Thrombosis; Thrombus; Time; Tissues; Training; United States; Universities; Validation; Work; World Health Organization; acute coronary syndrome; base; calcification; cancer imaging; cardiovascular imaging; cardiovascular visualization; career; career development; glucose uptake; image reconstruction; imaging modality; imaging system; improved; in vivo; information gathering; lens; luminescence; macrophage; medical schools; meetings; miniaturize; molecular imaging; molecular marker; novel; optical imaging; plaque lesion; prevent; professor; programs; quantitative imaging; research study; sudden cardiac death; tomography; uptake

 DESCRIPTION (provided by applicant): This research proposal describes a five-year career development and training plan to prepare the candidate, Dr. Raiyan T. Zaman, for a career as an independent investigator. This program will build on Dr. Zaman's background as an Electrical and Biomedical Engineer with expertise in development of novel imaging system to investigate and characterize atherosclerotic vulnerable plaque. The primary Mentor is Dr. Michael V. McConnell who is a Professor of Cardiovascular Medicine of the Department of Medicine at the Stanford University School of Medicine. Also, co-Mentor Dr. Lei Xing is the Director of Radiation Physics Division of the Department of Radiation Oncology at the Stanford University School of Medicine. The proposed Mentors are expert in cardiovascular imaging, molecular imaging, and imaging reconstruction. The K99 phase will consist of structured mentorship by the mentors, complementary meeting with an advisory committee, a novel research project, and a program of career transition. In her preliminary studies, Dr. Zaman has developed a novel catheter based radionuclide optical imaging system in bench-top setting and validated the system in ex vivo murine atherosclerotic plaque. The system successfully detected atherosclerotic plaque by a novel scintillating balloon with a molecular probe, 18F-FDG. Dr. Zaman demonstrated vulnerable plaque inside carotid artery provided 4× higher radio-luminescence signal compared to control. To date the candidate has accrued the technical competencies necessary to conduct the proposed research on vulnerable plaque such as inflamed thin-cap fibro atheroma (TCFA), which is thought to account for 60% to 70% of coronary events. The overall goal of this project is to improve our understanding of atherosclerotic plaques characteristics and pathobiology within the coronary arteries. To address this overarching goal a novel intravascular dual-modality fiber-optic catheter radionuclide imaging (CRI) and 4D photoacoustic tomography (PAT) imaging system will be developed for molecular imaging of glucose uptake by metabolically active vulnerable plaque and gather information on plaque constituents. The current clinical paradigm for detecting CAD is angiography, which only evaluates the luminal encroachment of the disease, without providing information about plaque extent, content, and biology. Several study showed that 18F-FDG, a molecular probe, is considered to be a marker of metabolically active ("vulnerable") plaques due to its uptake by inflammatory macrophages in the carotid and aorta. The major advantage of using 18F-FDG for vulnerable plaque detection is that it is FDA approved for cardiac and cancer imaging; thus, clinical transition may be more easily achieved. However, 18F-FDG detection in coronary plaque is still challenging due to their small size, motion, and obscuring signal by adjacent myocardium. These challenges have spurred the long-term goal of this research proposal to develop superior approaches to image coronary arterial inflammation and better define the TCFA constituents. In Specific Aim 1 during K99 phase, the novel dual-modality CRI-PAT imaging system will be built and the CRI and PAT part of the system will be tested separately on ex vivo aortic rabbit plaques (post IV injection of 18F-FDG) and postmortem human coronary plaques from autopsy specimens, respectively. These results will be correlated with histological and immunohistochemistry studies. In addition, these findings will be validated through IVIS-200 and autoradiography. A quantitative image map of the plaque constituents will be developed containing information on fatty acid, lipid or cholesterol, beta-carotene, elastin, collagen, and calcification. In the Specific Aim 2 during R00 phase, the candidate will use a comprehensive approach to test the system in in vivo rabbit aorta and will build data base on plaque constituents. In Specific Aim 3 during R00 phase, the CRI-PAT system will be used to evaluate the safety of the system in in vivo pig model as precursor to human testing. The evidence of injury and thrombosis will be assessed by autopsy. In addition, stable plaque, minimally inflamed fibrous lesion (created by balloon injury), will be compared to vulnerable plaque, inflamed thrombus lesion (created by copper stenting), by CRI-PAT. These results will be validated with autoradiography and histology/immunohistochemistry study. Dr. Zaman's ultimate goal is to use this information to characterize the vulnerable plaque by novel imaging modalities. Collectively, the proposed research work will elucidate novel imaging technology that will identify the vulnerable from stable plaque and characterize the vulnerable plaque with information on plaque constituents.

 描述（由适用提供）：本研究建议描述了一项为期五年的职业发展和培训计划，以准备候选人Raiyan T. Zaman博士作为独立调查员的职业。该计划将基于扎曼博士的背景作为电气和生物医学工程师，该工程师在开发新成像系统方面具有专业知识，以调查和表征动脉粥样硬化易受攻击的斑块。主要导师是斯坦福大学医学院医学系心血管医学教授Michael V. McConnell博士。此外，同事Lei Xing博士是斯坦福大学医学院辐射肿瘤学系辐射物理部主任。拟议的导师是心血管成像，分子成像和成像重建方面的专家。 K99阶段将包括导师的结构化心态，与咨询委员会的完整会议，新的研究项目和职业过渡计划。在她的初步研究中，Zaman博士在台式设置中开发了一种新型的基于导管的放射性光学成像系统，并验证了离体鼠动脉粥样硬化斑块中的系统。该系统通过用分子探针（18f-fdg）成功地检测到动脉粥样硬化斑块。与对照相比，扎曼博士证明了颈动脉内部易受攻击的斑块。迄今为止，候选人累积了对拟议的易受伤害斑块进行研究所需的技术能力，例如发炎的薄型纤维纤维动脉瘤（TCFA），该研究被认为占冠状动脉事件的60％至70％。该项目的总体目标是提高我们对冠状动脉动脉中动脉粥样硬化斑块的特征和病理学的理解。为了解决这个总体目标，一种新型新型的血管内双模式性纤维纤维导管放射性成像（CRI）和4D光声断层扫描（PAT）成像系统将开发出来，以通过代谢活跃的易受活跃的易受伤害的斑块对葡萄糖吸收的分子成像进行分子成像，并收集有关斑块构成的信息。当前用于检测CAD的临床范例是血管造影，它仅评估疾病的管腔加密，而无需提供有关斑块范围，含量和生物学的信息。几项研究表明，18F-FDG是一种分子探针，被认为是代谢活性（“脆弱”）斑块的标志，这是由于颈动脉和主动脉中的炎症性巨噬细胞吸收了它。使用18F-FDG进行脆弱的斑块检测的主要优点是，它已被FDA批准用于心脏和癌症成像。因此，临床过渡可能更容易实现。然而，由于冠状斑块中的18F-FDG检测仍然是挑战，因为它们的尺寸小，运动和相邻的心肌掩盖了信号。这些挑战刺激了这项研究建议的长期目标，即开发出较高的冠状动脉注射方法并更好地定义TCFA构建体。在K99阶段的特定目标1中，将建立新型的双模式CRI-PAT成像系统，并且系统的CRI和PAT将在离体前向兔子斑块上分别测试（IV后注射后注射后 分别来自尸检标本的18F-FDG）和尸体后冠状动脉斑块。这些结果将与组织学和免疫组织化学研究相关。此外，这些发现将通过IVIS-200和放射自显影进行验证。将开发斑块构成的定量图像图，其中包含有关脂肪酸，脂质或胆固醇，β-胡萝卜素，弹性蛋白，胶原蛋白和钙化的信息。在R00阶段的特定目标2中，候选人将采用一种全面的方法来测试体内兔主动脉系统，并将建立斑块构成的数据基础。在R00阶段的特定目标3中，CRI-PAT系统将用于评估体内猪模型作为人体测试前体的安全性。受伤和血栓形成的证据将通过尸检评估。此外，将将稳定的斑块，微小发炎的纤维病变（由气球损伤产生）与脆弱的斑块，发炎的血栓病变（由铜支架产生），由CRI-PAT进行比较。这些结果将通过自显影和组织学/免疫组织化学研究来验证。 Zaman博士的最终目标是使用这些信息来表征新型成像方式的脆弱牌匾。拟议的研究工作总的来说，将阐明新颖的成像技术，这些技术将从稳定的斑块中识别出易受伤害的斑块，并用斑块构成的信息来表征脆弱的牌匾。