HARDI Mapping of Disease Effects on the Brain

描述（由申请人提供）：该项目推进了高角度分辨率扩散成像（HARDI）的最新技术，这是一种强大的新成像方法，可以以惊人的精度解析大脑中的纤维通路。结合NIH资助的国家神经影像资源（加州大学洛杉矶分校），明尼苏达大学磁共振研究中心和西门子公司研究的专业知识，我们的目标是证明HARDI在评估艾滋病毒/艾滋病和阿尔茨海默病（AD）的临床重要脑变性方面提供了新的重要信息，扩展了我们的初步发现，揭示了这些疾病如何在活脑中动态传播。HARDI在多达256个不同的方向上向大脑施加磁场梯度，以精确地详细描述大脑中纤维的方向、路径和完整性。如果没有新的数学将这些信号视为黎曼流形，HARDI数据集还不能在不同学科之间进行比较。本项目提供了这些工具。我们的研究将（1）推进数学-部分基于几何，统计和黎曼流形-从HARDI中提取信息，（2）量化HARDI可以在多大程度上提高我们对大脑退化的理解，以及影响它的因素。使用HARDI图像中的额外细节，我们将开发一种方法，使大规模的多学科比较HARDI图像，通过在受试者之间流畅地对齐3D图像（目标1;多受试者对齐）。这是对疾病进行人群研究的第一步，例如，比较患者群体中的纤维完整性以检查基因或治疗效果，或将患者与标准数据库进行比较。对幻影和合成数据的验证是所有目标的关键部分。在目标2（分割和连通性映射）中，我们将开发算法来映射白色物质连通性，并根据HARDI的完整角度信息识别大脑中临床重要的纤维通路。在目标3（HARDI统计）中，优化的基于体素的统计将在人群中逐点比较HARDI数据，以识别系统性纤维缺陷，将纤维完整性和连接性与正常参考人群进行比较。在目标4（脑退化的HARDI地图）中，我们将评估HARDI揭示AD和HIV相关脑退化的新描述符：我们已经大量发表的两种疾病，其中严重缺乏白色退化的措施。AD和HIV的社会负担正在增加; HIV影响全球4000万人，仅在美国就影响450万人;每个人都有风险。我们强大的大脑白色物质退化标记将帮助我们确定HARDI增加的分辨率提供了多少好处。这种新的分析方法将大大提高我们理解病理性脑退化的能力，提供灵敏的新措施来跟踪它。这对药物试验和患者监测具有直接价值。一如既往，我们将与50多个合作实验室共享所有算法、协议和图像。公共卫生相关性：该项目开发的工具可以释放HARDI（高角度分辨率扩散成像）的全部功能，以推进大脑的临床研究。HARDI在多达256个不同的方向上向大脑施加磁场梯度，以精确地详细描述纤维及其连接的方向、路径和完整性。我们将评估HARDI以了解和揭示阿尔茨海默病和艾滋病毒相关脑白色变性的新描述符-对艾滋病毒药物试验和患者监测具有直接价值，艾滋病毒影响全球4000万人，AD影响美国450万人。

DESCRIPTION (provided by applicant): This project advances the state-of-the-art in High-Angular Resolution Diffusion Imaging (HARDI), a powerful new imaging approach that can resolve fiber pathways in the brain with spectacular precision. Uniting expertise at an NIH-funded National Neuroimaging Resource (at UCLA), the University of Minnesota Center for Magnetic Resonance Research, and Siemens Corporate Research, we aim to demonstrate that HARDI provides new and vital information in assessing clinically important brain degeneration in HIV/AIDS and Alzheimer's Disease (AD), extending our initial findings that revealed how these diseases spread dynamically in the living brain. HARDI applies magnetic field gradients to the brain, in up to 256 different directions, to precisely detail the directions, pathways, and integrity of fibers in the brain. HARDI datasets cannot yet be compared across subjects without new mathematics that treats these signals as lying in Riemannian manifolds. This project provides those tools. Our research will (1) advance the mathematics - based in part on geometry, statistics, and Riemannian manifolds - to extract information from HARDI, and (2) quantify how much HARDI can improve our understanding of brain degeneration, and what factors affect it. Using the extra detail in HARDI images, we will develop a method to enable large-scale multi-subject comparison of HARDI images, by fluidly aligning 3D images across subjects (Aim 1; Multi-subject Alignment). This is the first step towards population studies of disease, e.g., comparing fiber integrity across patient populations to examine gene or treatment effects, or comparing a patient with a normative database. Validation on phantoms and synthetic data is a key part of all Aims. In Aim 2 (Segmentation and Connectivity Mapping), we will develop algorithms to map white matter connectivity, and identify clinically important fiber pathways in the brain, based on the full angular information of HARDI. In Aim 3 (HARDI Statistics), optimized voxel-based statistics will compare HARDI data, point-by-point, across populations, to identify systematic fiber deficits, comparing fiber integrity and connectivity with a normal reference population. In Aim 4 (HARDI Maps of Brain Degeneration), we will evaluate HARDI for revealing new descriptors of AD and HIV-related brain degeneration: two illnesses on which we have published prolifically, where measures of white matter degeneration are sorely lacking. The societal burden of AD and HIV is growing; HIV affects 40 million people worldwide, and AD affects 4.5 million individuals in the U.S. alone; everyone is at risk. Our powerful markers of brain white matter degeneration will help us determine how much benefit HARDI's added resolution provides. This new analytic approach will greatly advance our ability to understand pathological brain degeneration, providing sensitive new measures to track it. This has immediate value for drug trials and patient monitoring. As always, we will share all algorithms, protocols, and images, with 50+ collaborating laboratories. PUBLIC HEALTH RELEVANCE: This project develops tools that unleash the full power of HARDI (high-angular resolution diffusion imaging) to advance clinical studies of the brain. HARDI applies magnetic field gradients to the brain in up to 256 different directions to precisely detail the directions, pathways, and integrity of fibers and their connections. We will evaluate HARDI for understanding and revealing new descriptors of Alzheimer's Disease and HIV-related brain white matter degeneration - with immediate value for drug trials and patient monitoring in HIV, which affects 40 million people worldwide, and in AD, which affects 4.5 million individuals in the U.S. alone.