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

三维微电极传感与血流储备分数联合检测高脂斑块 年，从战场返回的退伍军人中，动脉粥样硬化和代谢性疾病正在增加。 阿富汗和中东。动脉粥样硬化是一种全身性疾病;然而，其表现往往是 单个斑块的局部和偏心性以及破裂是心肌梗死的主要潜在机制。 梗塞和中风。易于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。根据随机临床试验，美国心脏协会 指南建议常规测量血流储备分数（FFR），定义为 通过狭窄病变的压力（P下游/P上游），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，患者被转诊接受冠状动脉血运重建，例如，支架展开 和抗血小板治疗。尽管如此，最近五年的FAME（部分流量储备）结果 与血管造影进行多支血管评价）2项试验显示死亡或心肌梗死无差异 FFR引导的经皮冠状动脉介入治疗（PCI）与最佳药物治疗之间的关系 稳定CAD。因此，易于破裂的代谢不稳定斑块的实时检测仍然是一个未满足的要求。 临床挑战我们以前的研究表明，腔内电化学阻抗 光谱（EIS）区分与氧化应激相关的动脉粥样硬化前病变 新西兰白色（NZW）兔。具体来说，血管壁含有氧化低密度脂蛋白（oxLDL） 表现出很高的EIS幅度。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）使钙化血管结节不稳定。在这 背景下，我们寻求开发一种电化学策略，以确定明显稳定，但代谢活性 (with FFR > 0.8）诊断期间含有oxLDL负载单核细胞-巨噬细胞（泡沫细胞）的病变 动脉造影我们假设将三维电化学阻抗谱与血流储备分数相结合 压力传感器允许检测富含oxLDL的病变，以提高必要的测量的准确性。 干预为了验证我们的假设，我们有三个具体目标。在目标1中，我们将集成一个12点三维 电极阵列允许高空间和角度分辨率，具有压力传感器， 载oxLDL的斑块。在目标2中，我们将确定3-D 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）+脂肪喂养中富含泡沫细胞的动脉粥样硬化病变 新西兰兔子在目标3中，我们将建立一个颈动脉破裂倾向斑块的3-D EIS标测。 猪模型总之，用动物模型建立活动性脂质负荷病变的三维电化学标测 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， 提高对退伍军人进行必要干预的准确性。

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.