Neural substrates of diffusion imaging in cognitively aging rhesus monkeys

描述（由申请人提供）：在大脑成熟和衰老期间识别和跟踪大脑结构变化的能力对于我们理解大脑功能至关重要，并且在临床研究中至关重要。虽然人类大脑的死后研究可以提供关于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，并且样本量很小。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，后处理技术可以分析整个大脑，提供解剖学上的特定数据，从而可以研究成像和功能之间的关系。扩散MRI和纤维束成像的最新发展已经揭示了猴子（Makris等人，2007）和人类（Voineskos等人，2012年）。不幸的是，这种成像变化的生物学基础在很大程度上是推测性的（Paus 2010），因此组织学特征的成像测量的特异性是未知的。缺乏这种“验证”主要是由于无法对人类的脑组织和成像进行良好的控制研究。在这个应用中，我们提出了一个多学科的研究，使用恒河猴模型的正常老化。这是由三名PI合作实现的，他们在MRI成像，形态测量学，神经解剖学和认知老化方面具有独特和互补的专业知识。我们有超过50只正常衰老的恒河猴，年龄从5岁（年轻成年人）到30岁以上（老年人中最年长的）不等。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的存档、冷冻保护、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，以及3）。开发必要的免费成像工具，以实现本提案的目标。这项拟议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，并提供组织验证的成像措施的理解，可应用于正常人类衰老以及许多其他临床人群的研究，包括创伤性脑损伤，多发性硬化症和精神分裂症。

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.