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

• 批准号: 10436777
• 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
• 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/10436777
• 关键词: 3-Dimensional; Afghanistan; American Heart Association; Angiography; Animal Model; Apolipoprotein A-I; Area; Arterial Fatty Streak; Atherosclerosis; Cardiometabolic Disease; 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; 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; Vascular calcification; Veterans; Visualization; base; calcification; cerebrovascular; electric impedance; flexibility; improved; macrophage; monocyte; multidisciplinary; oxidized lipid; oxidized low density lipoprotein; peptidomimetics; percutaneous coronary intervention; personalized intervention; porcine model; pre-clinical; pressure; pressure sensor; response; sensor; ultrasound

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.

三维微电极传感与分数流储备相结合的富脂斑块研究 动脉粥样硬化和代谢性疾病在我们从战场归来的退伍军人中呈上升趋势 阿富汗和中东。动脉粥样硬化是一种全身性疾病；然而，它的表现往往是 局灶性斑块和偏心性斑块破裂是心肌梗死的主要潜在机制 脑梗塞和中风。容易破裂的斑块含有高水平的氧化应激和炎症活性。 部分原因是氧化的脂类和泡沫细胞。基于随机临床试验，美国心脏协会 指南建议常规测量分数流量储备(FFR)，定义为 狭窄病变(P下行/P上游)的压力，以确定冠状动脉的适应症 冠心病(CAD)患者的血管重建。对于FFR&GT；0.8，患者接受 医疗优化；对于FFR≤0.8，患者被转介进行冠状动脉血运重建，例如支架部署 和抗血小板治疗。然而，FAME(部分流动储量)最近五年的成果 与血管造影术用于多支血管评估)2试验显示死亡或心肌梗死无差异 FFR引导下经皮冠状动脉介入治疗与最佳药物治疗的比较 稳定的CAD。因此，对容易破裂的代谢不稳定斑块的实时检测仍然是一个未达到的目标。 临床挑战。我们先前的研究表明，管腔内的电化学阻抗 光谱学(EIS)鉴别脂肪喂养的新生动物中与氧化应激相关的动脉粥样硬化前病变 新西兰白兔(NZW)。具体地说，血管壁含有氧化型低密度脂蛋白(OxLDL) 表现出较高的EIS震级。同时，内膜单核细胞和oxLDL在血管病变的各个阶段都是有害的。 动脉粥样硬化，通过诱导基质金属蛋白酶(MMP)使钙化血管结节不稳定。在这 背景下，我们试图开发一种电化学策略来识别表面上稳定但代谢活性 (FFR&GT；0.8)诊断过程中含有oxLDL的单核巨噬细胞(泡沫细胞)的病变 血管造影术。我们假设将三维电化学阻抗谱与FFR相结合 压力传感器允许检测富含oxLDL的病变，以提高必要的准确性 干预。为了检验我们的假设，我们有三个具体目标。在目标1中，我们将积分一个12点的3-D 电极阵列允许高空间和角度分辨率，并带有压力传感器，以增强对 富含oxLDL的斑块。在目标2中，我们将确定三维EIS图谱对oxLDL的敏感性和特异性。 脂肪喂养与D-4F(一种载脂蛋白A-I模拟肽)+脂肪喂养的富含泡沫细胞的动脉粥样硬化病变 新西兰大白兔。在目标3中，我们将在易破裂的颈动脉斑块中建立3D EIS图。 猪模。总之，用动物模型建立活动性脂质损伤的三维电化学图 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的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。