MRI OF HIV-INDUCED NEUROPATHY

HIV 引起的神经病变的 MRI

• 批准号: 8357700
• 负责人: MICHAEL DUFF DAVIS
• 金额: $ 0.7万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357700
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Animal Model; Animals; Architecture; Blood flow; Brain; Cerebrum; Elderly; Exhibits; Fiber; Funding; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; Human; Image; Imaging Techniques; Individual; Infection; Macaca mulatta; Magnetic Resonance Imaging; Manuals; Measurement; Measures; Modeling; Motor; National Center for Research Resources; National Institute of Allergy and Infectious Disease; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Neurons; Oxygen; Pan Genus; Phase; Population; Positron-Emission Tomography; Primates; Principal Investigator; Relative (related person); Research; Research Infrastructure; Resources; Scanning; Sensitivity and Specificity; Source; Speed; United States National Institutes of Health; age related; aged; aging brain; base; brain metabolism; cohort; cost; experience; gray matter; neuroimaging; nonhuman primate; tool; trend; white matter; young adult

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. This project seeks to validate the chimpanzee as a valuable non-human primate animal model with which to study brain aging using safe, non-invasive imaging techniques and assessments of motor dexterity and function. The chimpanzee brain exhibits similarities to normal and perturbed (e.g., Alzheimer's) human aging. These studies seek to: 1) develop non-invasive quantitative neuroimaging-based measurements of cerebral integrity in the brains of chimpanzees, 2) compare cerebral architecture in young vs. aged adults to validate the chimpanzee as a NHP model of human aging, and 3) validate assessment of motor slowing using a task previously used in rhesus monkeys. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have the potential of being ideal tools with which to non-invasively and non-destructively evaluate longitudinal degenerative changes in this valuable NHP species through intra-subject serial scanning. We will attempt to demonstrate sensitivity and specificity of cerebral neurodegeneration in the chimpanzee and estimate the magnitude of cerebral changes that normal (and, later, HIV-positive chimps) experience during their lifetime by performing analysis of statistical power and population effects. This will be carried out using multi-modal MRI for quantifying anatomical features (gray matter neurons and white matter fiber tracts) and using PET for measuring aging changes in brain metabolism (neuronal activity), blood flow and oxygen utilization. We will also quantify age-related changes in fine motor function, including measures of manual dexterity, manual speed, and motor coordination. Assessment of these functions will be made by providing chimpanzees relative simple, yet effective, tasks. If the preliminary results obtained with this project show promise in delineating age-related trends in structural brain differences, then the longer range goal of this project will be to seek NIH (e.g., NIA, NIAID or NINDS) R01 funding to: a) expand the numbers in both the young-adult and old-adult normal cohorts sufficiently in order to reach adequate statistical power analysis, and b) assess the influence of HIV infection in accelerating these age-dependent differences and/or whether infection promotes distinct neuropathological changes and how any changes might relate to infection duration. In this second phase, we also expect to image individual animals during age progression through multiple scans across a 5 year period.

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 而子项目的主要调查员可能是由其他来源提供的， 包括其它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。 该项目旨在验证黑猩猩是一种有价值的非人类灵长类动物模型，可以使用安全、非侵入性成像技术和运动灵巧性和功能评估来研究大脑衰老。 黑猩猩的大脑表现出与正常和扰动的相似之处（例如，老年痴呆症）人类衰老。 这些研究旨在：1）开发基于非侵入性定量神经成像的黑猩猩大脑完整性测量，2）比较年轻与老年人的大脑结构，以验证黑猩猩作为人类衰老的NHP模型，3）使用先前在恒河猴中使用的任务验证运动减慢的评估。 磁共振成像（MRI）和正电子发射断层扫描（PET）有可能成为理想的工具，通过受试者内连续扫描，非侵入性和非破坏性地评价这种有价值的NHP物种的纵向退行性变化。我们将试图证明黑猩猩脑神经退行性变的敏感性和特异性，并通过分析统计功效和群体效应来估计正常（以及后来的HIV阳性黑猩猩）在其一生中经历的脑变化的幅度。 这将使用多模态MRI来量化解剖特征（灰质神经元和白色物质纤维束），并使用PET来测量脑代谢（神经元活动）、血流量和氧利用的老化变化。我们还将量化精细运动功能与年龄相关的变化，包括手部灵巧性、手部速度和运动协调性的测量。 对这些功能的评估将通过提供给黑猩猩相对简单但有效的任务来进行。 如果该项目获得的初步结果显示出描绘脑结构差异中与年龄相关的趋势的希望，那么该项目的长期目标将是寻求NIH（例如，NIA、NIAID或NINDS）R 01资助：a）充分扩大成年人和老年人正常队列的数量，以达到充分的统计功效分析，和B）评估HIV感染对加速这些年龄依赖性差异的影响和/或感染是否促进明显的神经病理学变化，以及任何变化如何与感染持续时间相关。 在第二阶段，我们还希望在5年的时间内通过多次扫描对个体动物的年龄增长进行成像。