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Detection of plaque based macrophages with light

用光检测基于斑块的巨噬细胞

基本信息

批准号：
8394614
负责人：
MARC David FELDMAN
金额：
--
依托单位：
SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8394614
关键词：
Aorta Arterial Fatty Streak Atherosclerosis Biological Biology Biomedical Engineering Blood Blood Chemical Analysis Blood Circulation Blood Vessels Cardiac Cardiac Catheterization Procedures Cardiovascular system Catheterization Cause of Death Cells Cerebrum Cessation of life Chemical Engineering Clinical Research Coin Collaborations Collection Colloids Contrast Media Coupled Data Detection Development Dextrans Dose Excretory function Flow Cytometry Fluorescence Future Goals Gold Growth Half-Life Hemoglobin Hepatic Histology Image Imaging Techniques Infiltration Intravenous Kidney Label Laboratories Lasers Lead Letters Light Lipids Liquid substance Liver Magnetic Resonance Angiography Matrix Metalloproteinases Mechanics Methodology Motion Myocardial Infarction Nanotechnology Optical Coherence Tomography Optics Organ Oryctolagus cuniculus Pathologic Pathway interactions Patients Peripheral Catheterization Peripheral Vascular Diseases Phase Photophobia Physicians Physiologic pulse Production Property Public Health Relaxation Research Resolution Risk Rupture Scientist Sensitivity and Specificity Shoulder Signal Transduction Smooth Muscle Myocytes Societies Specificity Stroke Surface System Techniques Time Tissues Toxic effect Translating Translations Ultrasonography Veterans abstracting acute coronary syndrome base cell type cellular imaging density design dextran eosinophil in vivo iron oxide light scattering macrophage member multidisciplinary nanocage nanometer nanoparticle nanorod nanoshell novel optical imaging particle patient population prevent programs public health relevance receptor research study surface coating time use uptake

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract The pathologic features that predict atherosclerotic plaque rupture are large lipid collections, thinning of the fibrous cap, and infiltration of macrophages. Optical Coherence Tomography (OCT) has already been demonstrated to accurately image thin fibrous caps and large lipid cores. We now propose an approach which will detect macrophages in vulnerable plaque with OCT in patients at the time of catheterization. We demonstrate that by labeling plaque-based macrophages with intravenous gold nanoparticles we can detect the presence of macrophages for the first time using phase-sensitive OCT coupled with a stimulating laser. In this approach, optical nanoparticles engulfed by plaque-based macrophages are put into nanometer (nm) motion via thermal expansion and relaxation due to application of a pulsed laser, and this motion detected with a phase-sensitive OCT system. We have also developed novel optical nanoparticles for this approach which are excited by light maximally at a wavelength of 700-800 nm, to prevent laser interaction with competing plaque components such as hemoglobin, lipid, and arterial wall which maximally absorb light at 500-600 nm. Due to their multi-faceted surface, we have coined the term "nanorose" to describe these nanoparticles. To demonstrate cellular imaging of macrophages in intact plaque, we propose the following specific aims: Specific Aim # 1 - Specificity and sensitivity of nanoparticle (nanorose) uptake. 1.1 We will synthesize and fully characterize nanorose with controlled size, and gold and dextran amounts, to achieve strong NIR absorbance and specific cell (macrophage) uptake. 1.2 We will demonstrate specific uptake of nanorose by macrophages as opposed to endothelial and smooth muscle cells in culture via the use of flow cytometry. 1.3 We will inject nanorose iv into atherosclerotic rabbits, and perform detailed histology with fluorescence microcopy to determine both the minimal detectable dose and the specificity of nanorose uptake in plaque. Specific Aim # 2 - Ex vivo and in vivo OCT imaging of macrophages in rabbit atherosclerotic aortas with nanorose. 2.1 We will inject nanorose iv into atherosclerotic rabbits, perform OCT imaging of ex vivo aortic tissue, and compare these images with histology via RAM-11 identification of macrophages, and hyperspectral imaging of nanorose. 2.2 We will inject nanorose iv into atherosclerotic rabbits, repeat each of the histological experiments in section 2.1, but with in vivo OCT imaging. Specific Aim # 3 - Excretion and toxicity of nanorose. 3.1 We will characterize the excretion pathway of nanorose (hepatic vs. renal, organs of distribution, and blood half-life). 3.2 We will demonstrate in rabbits the absence of organ toxicity via blood chemistry for evidence of hepatic and renal damage, eosinophil production, and post-mortem examination. These studies will also be performed in collaboration with the Nanotechnology Characterization Laboratory (see letter of support).

描述(由申请人提供)：项目摘要/摘要预测动脉粥样硬化斑块破裂的病理特征是大量脂质聚集、纤维帽变薄和巨噬细胞浸润。光学相干层析成像(OCT)已经被证明可以准确地成像薄的纤维帽和大的脂核。我们现在提出一种方法，在插管时用OCT检测患者易损斑块中的巨噬细胞。我们证明，通过静脉注射金纳米颗粒标记基于斑块的巨噬细胞，我们可以首次使用相敏OCT结合刺激性激光来检测巨噬细胞的存在。在这种方法中，被基于斑块的巨噬细胞吞噬的光学纳米颗粒在脉冲激光的作用下通过热膨胀和松弛进入纳米(Nm)运动，并通过相敏OCT系统检测到这种运动。我们还开发了用于这种方法的新型光学纳米颗粒，它们最大限度地由波长700-800 nm的光激发，以防止激光与竞争的斑块成分相互作用，如血红蛋白、脂质和动脉壁，它们最大限度地吸收500-600 nm的光。由于它们的表面多面性，我们创造了“纳米糖”这个术语来描述这些纳米颗粒。为了展示完整斑块中巨噬细胞的细胞成像，我们提出了以下特定目标：特定目标#1-纳米颗粒(纳米糖)摄取的特异性和敏感性。1.1我们将合成并充分表征大小可控、金和葡聚糖含量可控的纳米糖，以实现强大的近红外吸收能力和特定细胞(巨噬细胞)的摄取。1.2我们将通过使用流式细胞术证明巨噬细胞在培养中对纳米糖的特异性摄取，而不是内皮细胞和平滑肌细胞。1.3我们将纳米糖静脉注射到动脉粥样硬化兔体内，并用荧光显微镜进行详细的组织学检查，以确定斑块中纳米糖摄取的最小可检测剂量和特异性。特定目标#2-使用纳米糖对兔动脉粥样硬化动脉内巨噬细胞进行OCT成像。2.1我们将纳米糖静脉注射到动脉粥样硬化兔体内，对体外主动脉组织进行OCT成像，并通过RAM-11巨噬细胞鉴定和纳米糖高光谱成像将这些图像与组织学进行比较。2.2我们将向动脉粥样硬化的兔体内注射纳米糖，重复2.1节中的每一项组织学实验，但要进行体内OCT成像。具体目标#3--纳米糖的排泄和毒性。3.1我们将描述纳米糖的排泄途径(肝与肾、分布器官和血液半衰期)。3.2我们将通过血液化学证明兔的器官没有毒性，以证明肝和肾损伤、嗜酸性粒细胞产生和尸检。这些研究还将与纳米技术表征实验室合作进行(见支持函)。