HARDI Mapping of Disease Effects on the Brain

描述（由申请人提供）：该项目推进了高角分辨率扩散成像（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。结合美国国立卫生研究院资助的国家神经成像资源（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为评估艾滋病毒/艾滋病和阿尔茨海默病（AD）的临床重要脑变性提供了新的重要信息，扩展了我们揭示这些疾病如何在活体大脑中动态传播的初步发现。HARDI将磁场梯度应用于大脑，在多达256个不同的方向上，以精确地详细描述大脑中纤维的方向，路径和完整性。如果没有将这些信号视为黎曼流形的新数学，HARDI数据集还不能跨学科进行比较。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、统计学和黎曼流形——从HARDI中提取信息，(2)量化HARDI能在多大程度上提高我们对大脑退化的理解，以及影响大脑退化的因素。利用HARDI图像中的额外细节，我们将开发一种方法，通过跨主题流畅地对齐3D图像来实现大规模的HARDI图像多主题比较（目标1；多主题对齐）。这是迈向疾病群体研究的第一步，例如，比较不同患者群体的纤维完整性以检查基因或治疗效果，或将患者与规范数据库进行比较。对幻影和合成数据的验证是所有Aims的关键部分。在目标2（分割和连接映射）中，我们将开发算法来绘制白质连接，并基于HARDI的完整角度信息识别大脑中临床上重要的纤维通路。在Aim 3 （HARDI统计）中，优化的基于体素的统计将逐点比较人群中的HARDI数据，以识别系统的光纤缺陷，并将光纤完整性和连通性与正常参考人群进行比较。在Aim 4（大脑退化的HARDI地图）中，我们将评估HARDI对AD和hiv相关的大脑退化的新描述：我们已经发表了大量关于这两种疾病的文章，其中白质退化的测量非常缺乏。阿尔茨海默病和艾滋病毒的社会负担正在增加；全世界有4000万人感染艾滋病毒，仅在美国就有450万人感染阿尔茨海默病；每个人都有风险。我们强大的脑白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，为跟踪它提供敏感的新措施。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充分发挥高角度分辨率扩散成像（HARDI）的力量，以推进大脑的临床研究。HARDI将磁场梯度应用于多达256个不同方向的大脑，以精确地详细描述方向，路径和纤维及其连接的完整性。我们将对HARDI进行评估，以了解和揭示阿尔茨海默病和艾滋病毒相关脑白质变性的新描述，这对艾滋病病毒的药物试验和患者监测具有直接价值，艾滋病病毒影响全球4000万人，阿尔茨海默病影响美国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.