MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY

早产儿视网膜病变中血管生成和细胞损伤的 MRI 生物标志物

基本信息

批准号：
7450075
负责人：
Junjie Chen
金额：
$ 21.76万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7450075
关键词：
Acetic Acid Acetic Acids Adult Adverse effects Area Binding Biological Markers Blindness Cell Hypoxia Cells Child Cornea Diagnostic Procedure Diffusion Diffusion Magnetic Resonance Imaging Disease Marker Disease Progression Early Diagnosis Fluorocarbons Gadolinium Hyperglycemia Hypoxia Imaging Techniques Integrins Invasive Lead Localized Magnetic Resonance Magnetic Resonance Imaging Malignant - descriptor Measures Medical Medical Imaging Methods Modeling Molecular Neonatal Operative Surgical Procedures Oryctolagus cuniculus Oxygen Oxygen Consumption Pathologic Neovascularization Patients Pentas Peripheral Pharmaceutical Preparations Photoreceptors Premature Infant Preventive Public Health Rattus Research Resolution Retina Retinal Retinal Detachment Retinal Diseases Retinal Neovascularization Retinopathy of Prematurity Rodent Specific qualifier value Surface Techniques Testing Tumor-Associated Vasculature Vision Visual system structure Weight angiogenesis antiangiogenesis therapy base cell injury cost diabetic diethylenetriamine experience indexing injured interest nanoparticle novel novel diagnostics photoreceptor degeneration prevent proliferative diabetic retinopathy retinal angiogenesis retinal ischemia tool

项目摘要

DESCRIPTION (provided by applicant): Proliferative retinopathy is a leading cause of blindness in adults and children. It is manifested as hypoxia induced malignant angiogenesis at retinal surface that will deteriorate vision and lead to retinal detachment to cause permanent vision loss. Medical therapy for proliferative retinopathy is non-effective. Surgical medical treatment to ablate peripheral retina is the method to prevent the disease progression at the cost of losing peripheral vision. This treatment has prominent side effects on the visual system and may not stop the disease progression in some patients. Current interests on developing more effective therapy for proliferative retinopathy are: to develop anti-angiogenesis drug that specifically inhibit retinal neovascularization; to explore predictive markers of the diseases for preventive therapy. We have developed high resolution magnetic resonance imaging (MRI) technique that specifies multiple retinal layers with layer specific T1, T2, and apparent diffusion coefficient (ADC) in rodents. Our preliminary studies have demonstrated that MRI is sensitive to cell injury after retinal ischemia or photoreceptor degeneration. We have also shown that 1v23-integrin targeted nanoparticles specifically bind to corneal neovasculature and provide localized MRI contrast in rabbits. Based on our preliminary result, we hypothesize that hypoxia induced retinal angiogenesis could be specifically delineated with molecular MRI using 1v23-integrin targeted nanoparticles. Hypoxia will also cause retinal cell injury that will result in changes in ADC before retinal angiogenesis. To test our hypothesis, a rat model of hypoxia induced retinal neovascularization is selected. We predict that 1v23-integrin targeted nanoparticles will specifically bind to retinal neovasculature for molecular MRI of retinal angiogenesis. We also expect changes in ADC in hypoxia injured retinal cells can be detected early with diffusion weighted magnetic resonance imaging. The proposed study, if successful, will provide novel MRI biomarkers for early diagnosis of retinal neovascularization that feature cell hypoxia and angiogenesis. PUBLIC HEALTH RELEVANCE: Retinal angiogenesis is the leading cause of blindness in premature infants and diabetic adults. The proposed research aims to develop techniques for early diagnosis of retinal angiogenesis using nanoparticles and non-invasive medical imaging method.

描述（由申请人提供）：增殖性视网膜病变是成人和儿童失明的主要原因。表现为视网膜表面缺氧诱发恶性血管生成，导致视力恶化，导致视网膜脱离，造成永久性视力丧失。增生性视网膜病的药物治疗无效。切除周边视网膜的手术治疗是防止疾病进展的方法，但代价是丧失周边视力。这种治疗对视觉系统有显着的副作用，并且可能无法阻止某些患者的疾病进展。目前对开发更有效的增殖性视网膜病治疗方法的兴趣是：开发特异性抑制视网膜新生血管形成的抗血管生成药物；探索疾病的预测标记以进行预防性治疗。我们开发了高分辨率磁共振成像 (MRI) 技术，可通过层特异性 T1、T2 和表观扩散系数 (ADC) 指定啮齿类动物的多个视网膜层。我们的初步研究表明，MRI 对视网膜缺血或光感受器变性后的细胞损伤敏感。我们还表明，1v23-整合素靶向纳米颗粒特异性结合角膜新生血管，并在兔子中提供局部 MRI 对比。根据我们的初步结果，我们假设缺氧诱导的视网膜血管生成可以使用 1v23-整合素靶向纳米颗粒通过分子 MRI 进行明确描绘。缺氧还会引起视网膜细胞损伤，从而导致视网膜血管生成前ADC发生变化。为了检验我们的假设，选择缺氧诱导视网膜新生血管形成的大鼠模型。我们预测 1v23-整合素靶向纳米颗粒将特异性结合视网膜新生血管，用于视网膜血管生成的分子 MRI。我们还期望通过弥散加权磁共振成像可以早期检测到缺氧损伤的视网膜细胞中 ADC 的变化。拟议的研究如果成功，将为早期诊断以细胞缺氧和血管生成为特征的视网膜新生血管提供新的 MRI 生物标志物。公共卫生相关性：视网膜血管生成是早产儿和糖尿病成人失明的主要原因。该研究旨在开发利用纳米粒子和非侵入性医学成像方法早期诊断视网膜血管生成的技术。