MRI OF HIV-INDUCED NEUROPATHY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目旨在验证黑猩猩是一个有价值的非人类灵长类动物模型，用来使用安全、非侵入性的成像技术和运动灵活性和功能的评估来研究大脑老化。黑猩猩的大脑表现出与正常和不安(例如阿尔茨海默氏症)人类衰老的相似之处。这些研究试图：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方法，2)比较年轻和老年成年人的大脑结构，以验证黑猩猩是否为人类衰老的NHP模型，以及3)验证使用以前在恒河猴身上使用的任务对运动减慢的评估。磁共振成像(MRI)和正电子发射断层扫描(PET)具有通过受试者内序列扫描非侵入性和非破坏性地评估这种有价值的NHP物种的纵向退行性变化的理想工具。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，并通过对统计能力和种群效应的分析，估计正常黑猩猩(以及后来的HIV阳性黑猩猩)在一生中经历的大脑变化的幅度。这将使用多模式磁共振成像来量化解剖特征(灰质神经元和白质纤维束)，并使用正电子发射计算机断层扫描(PET)来测量大脑代谢(神经元活动)、血流和氧气利用的衰老变化。我们还将量化与年龄相关的精细运动功能的变化，包括手动灵活性、手动速度和运动协调性的测量。这些功能的评估将通过为黑猩猩提供相对简单但有效的任务来进行。如果这个项目获得的初步结果在描绘大脑结构差异中与年龄相关的趋势方面显示出希望，那么这个项目的较长期目标将是寻求NIH(例如，NIA、NIAID或NINDS)R01资金：a)充分扩大青年-成人和老年-成人正常队列中的数量，以便进行充分的统计学力量分析，以及b)评估艾滋病毒感染在加速这些年龄相关差异方面的影响和/或感染是否促进明显的神经病理变化以及任何变化可能如何与感染持续时间相关。在第二阶段，我们还希望通过5年内的多次扫描，对年龄增长过程中的单个动物进行成像。

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.