Neural substrates of diffusion imaging in cognitively aging rhesus monkeys

描述（由申请人提供）：在大脑成熟和衰老过程中识别和跟踪大脑结构变化的能力是我们了解大脑功能的基础，也是临床研究的关键。虽然人类大脑的死后研究可以提供局部组织学变化的数据，但它们只是横截面的，大脑样本不是最佳的，而且样本量很小。相比之下，非侵入性体内成像可以为大量人群提供强大的纵向数据。此外，后处理技术使分析整个大脑成为可能，为研究成像和功能之间的关系提供了解剖学上的特定数据。扩散MRI和纤维束造影的最新进展揭示了猴子（Makris et al., 2007）和人类（Voineskos et al., 2012）的成像变化与认知衰老之间的相关性。不幸的是，这种影像学变化的生物学基础在很大程度上是推测性的（Paus 2010），因此影像学措施对组织学特征的特异性是未知的。缺乏这种“验证”主要是由于无法对人类脑组织和成像进行良好控制的研究。在这个应用程序中，我们提出了一个多学科的研究，使用恒河猴正常衰老模型。这是由三家pi合作实现的，他们在MRI成像，形态测量学，神经解剖学和认知衰老方面具有独特和互补的专业知识。我们有50多只正常衰老的恒河猴，男女皆有，年龄从5岁（年轻人）到30岁以上（老年人中年龄最大的）。最重要的是认知和DTI数据的可用性，这些数据可用于对所有这些猴子的存档、冷冻保护和未染色组织进行组织病理学验证。本提案的主要目的是：1)。建立个体弥散张量成像（DTI）指标对认知成熟和衰老的敏感性，2)。研究认知成熟和衰老过程中扩散变化的生物学基础；开发必要的免费成像工具，以实现本提案的目标。这项研究的结果将极大地影响我们对衰老过程及其机制的理解，并为正常人类衰老以及许多其他临床人群（包括创伤性脑损伤、多发性硬化症和精神分裂症）的研究提供组织有效的成像方法。

DESCRIPTION (provided by applicant): The ability to identify and follow structural brain changes during brain maturation and aging is both fundamental to our understanding of brain function, and crucial in clinical studies. While post-mortem studies of human brain can provide data on local histological changes, they are only cross sectional, brain samples are not optimal, and sample sizes are small. In contrast, non-invasive in vivo imaging can provide powerful longitudinal data for large populations. Moreover, post-processing techniques make it possible to analyze the entire brain, providing anatomically specific data that allows for investigating relationships between imaging and function. Recent developments in diffusion MRI and fiber tractography have revealed correlations between imaging changes and cognitive aging in both monkeys (Makris et al, 2007), and humans (Voineskos et al., 2012). Unfortunately, the biological underpinnings of such imaging changes are largely speculative (Paus 2010) and hence the specificity of imaging measures for histological features is unknown. The lack of such "validation" is largely due to the inability to conduct well-controlled studies of both brain tissu and imaging in humans. In this application we propose a multidisciplinary study using the rhesus monkey model of normal aging. This is enabled by a collaboration of three PIs, with unique and complementary expertise in MRI imaging, morphometry, neuroanatomy and cognitive aging. We have available a cohort of over 50 normal aging rhesus monkeys of both sexes, ranging in age from 5 (young adults) to over 30 (oldest of the old) years of age. Most important is the availability of cognitive and DTI data that can be used for histopathological validation of archived, cryoprotected, unstained tissue from all of these monkeys. The main aims of this proposal are: 1). To establish sensitivity of individual diffusion tensor imaging (DTI) metrics to cognitive maturation and aging, 2). To investigate biological underpinnings of diffusion changes during cognitive maturation and aging, and 3). To develop free imaging tools necessary to accomplish the goals of this proposal. The results of this proposed study will greatly impact our understanding of aging processes and their mechanisms and provide tissue validated understanding of imaging measures that can be applied to studies of normal human aging as well as many other clinical populations including traumatic brain injury, multiple sclerosis, and schizophrenia.