Integrating 3-D Intravascular Sensors with Fractional Flow Reserve for Lipid-Rich Plaques

将 3-D 血管内传感器与富脂斑块的血流储备分数相结合

基本信息

批准号：
9892828
负责人：
Rene R.S. Packard
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892828
关键词：
3-Dimensional Afghanistan American Heart Association Angiography Animal Model Apolipoprotein A-I Area Arterial Fatty Streak Atherosclerosis Cardiovascular Diseases Carotid Arteries Cessation of life Clinical Coronary Coronary Arteriosclerosis Coronary artery Detection Diagnostic Disease Electrodes Evaluation Exhibits Family suidae Fatty acid glycerol esters Flowcharts Foam Cells Frequencies Guidelines Gulf War Health High Fat Diet Histologic Individual Inflammatory Intervention Lesion Ligation Lipid-Laden Macrophage Lipids Maps Matrix Metalloproteinases Measurement Measures Medical Metabolic Metabolic Diseases Metabolic syndrome Microelectrodes Middle East Modeling Myocardial Infarction New Zealand Nodule Oryctolagus cuniculus Outcome Oxidative Stress Patients Penetration Phase Randomized Clinical Trials Reproducibility Resolution Risk Factors Rupture Sensitivity and Specificity Specimen Spectrum Analysis Stents Stroke Subendothelial Layer Systemic disease Testing Therapeutic Embolization Thinness Time Translations Ultrasonic Transducer Ultrasonography Vascular calcification Veterans Visualization base calcification cardiometabolism cerebrovascular electric impedance flexibility improved macrophage monocyte multidisciplinary oxidized lipid oxidized low density lipoprotein peptidomimetics percutaneous coronary intervention personalized intervention pre-clinical pressure pressure sensor response sensor

项目摘要

Integrating 3-D Micro-Electrode Sensing with Fractional Flow Reserve for Lipid-Rich Plaques Atherosclerosis and metabolic diseases are on the rise in our veterans returning from battlefields in Afghanistan and the Middle East. Atherosclerosis is a systemic disease; however, its manifestations tend to be focal and eccentric, and rupture of individual plaques is the primary underlying mechanism of myocardial infarction and stroke. Plaques prone to rupture contain high levels of oxidative stress and inflammatory activity in part due to oxidized lipids and foam cells. Based on randomized clinical trials, American Heart Association guidelines recommend the routine measurement of Fraction Flow Reserve (FFR), defined as the ratio of pressure across the stenotic lesions (Pdownstream/Pupstream), to determine the indication for coronary revascularization in patients with coronary artery disease (CAD). For FFR > 0.8, patients are treated with medical optimization; for FFR ≤ 0.8, patients are referred for coronary revascularization, e.g., stent deployment and antiplatelet therapy. Nevertheless, the recent five-year outcomes of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) 2 trial revealed no difference in death or myocardial infarction between FFR-guided percutaneous coronary intervention (PCI) and optimal medical therapy in patients with stable CAD. Thus, real-time detection of the metabolically unstable plaque prone to rupture remains an unmet clinical challenge. Our previous studies demonstrated that endoluminal electrochemical impedance spectroscopy (EIS) distinguishes pre-atherogenic lesions associated with oxidative stress in fat-fed New Zealand White (NZW) rabbits. Specifically, vessel walls harboring oxidized low density lipoprotein (oxLDL) exhibit high EIS magnitude. In parallel, intimal monocytes and oxLDL are deleterious at all stages of atherosclerosis, destabilizing calcific vascular nodules via induction of matrix metalloproteinases (MMP). In this context, we seek to develop an electrochemical strategy to identify apparently stable, but metabolically active (with FFR > 0.8) lesions containing oxLDL-laden monocyte-macrophages (foam cells), during diagnostic angiography. We hypothesize that integrating 3-D electrochemical impedance spectroscopy with FFR pressure sensors allows for detection of oxLDL-rich lesions to improve the accuracy of necessary intervention. To test our hypothesis, we have three Specific Aims. In Aim 1, we will integrate a 12-point 3-D electrode array permitting high spatial and angular resolution with pressure sensors to enhance detection of oxLDL-laden plaque. In Aim 2, we will determine the sensitivity and specificity of 3-D EIS mapping for oxLDL- laden, foam cell-rich atherosclerotic lesions in fat-fed vs. D-4F (an apolipoprotein A-I mimetic peptide) + fat-fed NZW rabbits. In Aim 3, we will establish 3-D EIS mapping in rupture-prone plaque in the carotid arteries of a pig model. Overall, establishing 3-D electrochemical mapping of active lipid-laden lesions with animal models of atherosclerosis provides a new strategy to identify metabolically active lesions for personalized intervention, and improve the accuracy of necessary intervention for our veterans.

将 3D 微电极传感与富脂斑块的分数流量储备相结合从战场归来的退伍军人中，动脉粥样硬化和代谢性疾病呈上升趋势阿富汗和中东地区动脉粥样硬化是一种全身性疾病；但其表现往往是。局灶性和偏心性，个别斑块的破裂是心肌损伤的主要机制。容易破裂的斑块含有高水平的氧化应激和炎症活性。部分原因是氧化脂质和泡沫细胞。根据美国心脏协会的随机临床试验。指南建议常规测量血流储备分数 (FFR)，定义为狭窄病变处的压力（Pdownstream/Pupstream），以确定冠状动脉的适应症冠状动脉疾病 (CAD) 患者的血运重建对于 FFR > 0.8，患者接受以下治疗：医疗优化；对于 FFR ≤ 0.8，患者被转诊进行冠状动脉血运重建，例如支架置入术尽管如此，FAME（血流储备分数）最近五年的结果。血管造影与多血管评估）2项试验显示死亡或心肌梗塞没有差异 FFR 引导下的经皮冠状动脉介入治疗 (PCI) 与最佳药物治疗之间的关系因此，实时检测容易破裂的代谢不稳定斑块仍然是一个未满足的问题。我们之前的研究表明腔内电化学阻抗。光谱学 (EIS) 区分脂肪喂养中与氧化应激相关的动脉粥样硬化前病变具体来说，新西兰白兔（NZW）的血管壁含有氧化低密度脂蛋白（oxLDL）。同时，内膜单核细胞和 oxLDL 在所有阶段都是有害的。动脉粥样硬化，通过诱导基质金属蛋白酶（MMP）破坏钙化血管结节。在背景下，我们寻求开发一种电化学策略来识别表面稳定但代谢活跃的（FFR > 0.8）诊断期间含有负载 oxLDL 的单核巨噬细胞（泡沫细胞）的病变我们一直在将 3D 电化学阻抗谱与 FFR 相结合。压力传感器可以检测富含 oxLDL 的病变，以提高必要的准确性为了检验我们的假设，我们有三个具体目标，在目标 1 中，我们将整合 12 点 3-D。电极阵列允许高空间和角度分辨率与压力传感器，以增强检测在目标 2 中，我们将确定 oxLDL- 的 3-D EIS 映射的敏感性和特异性。脂肪喂养与 D-4F（载脂蛋白 A-I 模拟肽）+ 脂肪喂养中充满、富含泡沫细胞的动脉粥样硬化病变在目标 3 中，我们将在 NZW 兔子的颈动脉中建立易破裂斑块的 3-D EIS 映射。总体而言，利用动物模型建立活性脂质损伤的 3D 电化学图谱。动脉粥样硬化的研究提供了一种新的策略来识别代谢活跃病变以进行个性化干预，并提高对退伍军人进行必要干预的准确性。