MRI OF ANGIOGENESIS AND VASCULATURE ALTERNATIONS IN ALZHEIMER'S DISEASE

阿尔茨海默病血管生成和血管变化的 MRI

• 批准号: 8362004
• 负责人: Kewen Cai
• 金额: $ 0.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362004
• 关键词: Affect; Alzheimer' s Disease; Angiogenesis Inhibitors; Biological Markers; Blood Vessels; Breathing; Cerebrum; Dementia; Development; Disease; Disease Progression; Early Diagnosis; Elderly; Funding; Grant; Hyperoxia; Hypoxia; Image; Imagery; Investigation; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Methods; Mus; National Center for Research Resources; Onset of illness; Pathology; Permeability; Pharmaceutical Preparations; Population; Principal Investigator; Relative (related person); Research; Research Infrastructure; Research Personnel; Resources; Signal Transduction; Source; Spin Labels; Techniques; Testing; Treatment Efficacy; United States National Institutes of Health; angiogenesis; base; blood oxygen level dependent; brain tissue; cost; novel; optical imaging; prevent; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Affecting 10% of the world's population, Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly. Despite enormous investigative efforts, the pathological basis for AD remains unclear. Recently, it was hypothesized that AD may be an angiogenesis-dependent disorder and anti-angiogenic drugs might be able to prevent and treat this disease. Researchers suggest that imaging vascular alterations, such as angiogenesis, could serve as a biomarker for AD disease onset and progression. Here we present the first MRI demonstration of AD associated angiogenesis by using a technique based on endogenous blood oxygenation level dependent (BOLD) effect. Relative to normoxia, hypoxia inhalation (8% O2) significantly reduces MR signal from cerebral vasculature, creating much higher BOLD effect than hyperoxia (100% O2). While signal from AD plaques and normal brain tissue is less sensitive to oxygenation changes, resulting in a clear cerebral vasculature image (CBV map), the relationship between AD plaque and vasculature network can be characterized. We demonstrate that the endogenous BOLD effect induced by hypoxia enables the visualization of angiogenesis and vasculature alterations associated with AD pathology in mice. It avoids confounding factor due to vessels permeability common in Dynamic Contrast Enhanced MRI (DCE-MRI) methods and produces much higher sensitivity than the endogenous contrast from Arterial Spin Labeling (ASL) MRI. With further development, MRI of angiogenesis and vasculature alternations could serve as a sensitive tool for investigation of AD pathology, early diagnosis and testing therapeutic efficacy of novel drugs.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 阿尔茨海默病（AD）是最常见的疾病之一，影响着世界上10%的人口 老年痴呆症的症状尽管做出了巨大的调查努力，但病理基础 AD仍不清楚。最近，有人假设AD可能是一种血管生成依赖性的疾病， 疾病和抗血管生成药物可能能够预防和治疗这种疾病。研究人员 这表明，成像血管改变，如血管生成，可以作为生物标志物， AD疾病发作和进展。在这里，我们提出了第一次MRI演示AD相关的血管生成，使用的技术基础上内源性血氧水平依赖（BOLD） 效果相对于常氧，低氧吸入（8%O2）显著降低了MR信号， 脑血管，产生比高氧（100%O2）更高的BOLD效应。而信号 AD斑块和正常脑组织对氧合变化的敏感性较低， 明确脑血管图像（CBV图），AD斑块与 可以表征脉管系统网络。我们证明了内源性BOLD效应 缺氧诱导的血管生成和血管系统改变的可视化 与小鼠AD病理学相关。它避免了由于血管渗透性引起的混淆因素 在动态对比增强MRI（DCE-MRI）方法中常见， 灵敏度高于动脉自旋标记（ASL）MRI的内源性造影剂。进一步 MRI对血管生成和血管系统的改变可以作为一个敏感的工具 用于AD病理学研究、早期诊断和新药疗效检测。