DTI and MRS Correlates of Aging in Monkeys

描述（由申请人提供）： 恒河猴是正常人类衰老的模型，能够在精心控制的条件下测试大脑生理学，神经化学和结构中与年龄相关的变化，从而避免混淆因素，这些因素会掩盖衰老对大脑的微妙影响。拟议的研究是一项多模态、横断面MRI/MRS研究，旨在检测猴脑中与年龄相关的变化。我们将使用扩散张量成像（DTI）监测猴脑的微观和宏观结构参数，使用高对比度/高分辨率MRI解剖图像监测体积测量的变化，以及使用磁共振波谱（MRS）非侵入性测量的猴脑神经化学特征的变化。在这个建议中，我们希望进行一个试点的多模式MRI/MRS研究三个年龄组的恒河猴（猕猴）。我们希望检查（1）额叶白色物质（WM）扩散各向异性的减少;（2）额叶灰质体积的减少;（3）代谢物浓度的变化，特别是额叶灰质和白色物质中的N-乙酰天冬氨酸（NAA）、肌醇、胆碱、谷氨酰胺和GABA。这些技术将用于对一小组控制良好的雄性和雌性猴进行初步研究。在这些研究之后，将处死猴，并进行脑组织的死后分析：（1）脑提取物的高分辨率高场NMR分析;（2）根据DTI和/或MR体积结果对似乎受到影响的脑区域进行组织学观察。这些数据将帮助我们检验年龄相关认知缺陷存在可靠MRI/MRS相关性的假设。我们的具体目标是：（1）收集关于衰老对猴脑影响的初步数据;（2）用相同大脑的尸检数据验证MRI/MRS结果。

DESCRIPTION (provided by applicant): The rhesus monkey is a model of normal human aging that enables testing age-related changes in brain physiology, neurochemistry and structure under carefully controlled conditions, thus avoiding confounding factors that obscure the sometimes subtle effects that aging has on the brain. The proposed study is a multimodal, cross-sectional MRI/MRS study that aims to detect age-related changes in the monkey brain. We will monitor microscopic and macroscopic structural parameters in the monkey brain using Diffusion Tensor Imaging (DTI), changes in volumetric measures using high-contrast/high resolution MRI anatomical images, as well as changes in the neurochemical profile of the monkey brain that can be non-invasively measured using Magnetic Resonance Spectroscopy (MRS). In this proposal we wish to perform a pilot multimodal MRI/MRS study on three age groups of rhesus monkeys (macaca mulatta). We wish to examine (1) reductions in frontal white matter (WM) diffusion anisotropy; (2) reductions in frontal gray matter volume; (3) changes in metabolite concentrations and in particular N-acetyl aspartate (NAA), myoinositol, choline, glutamine and GABA in frontal gray and white matter. These techniques will be used to perform a preliminary study on a small and well-controlled group of monkeys of both sexes. Following these studies, the monkeys will be sacrificed, and post-mortem analyses of brain tissue will be performed: (1) High resolution high-field NMR analysis of brain extracts; (2) histological observation of brain areas that appear to be affected according to the DTI and/or MR volumetric results.hese data will help us test the hypothesis that there is a solid MRI/MRS correlate of age-related cognitive deficits. Our specific aims are: (1) Collection of preliminary data on the effects of aging on the monkey brain; (2) Validation of the MRI/MRS findings with post-mortem data on the same brains.