Statistical models for multi-modal brain imaging studies of HIV-associated cognitive decline

 描述(由申请人提供)： HIV患者神经认知障碍及其进展的研究是一项涉及复杂数据结构的多方面努力。这些措施包括多模式脑成像措施以及纵向宿主和病毒标志物。探索这些数据的全部潜力需要 先进统计分析方法的应用和发展。这项提案将解决由圣路易斯华盛顿大学恩斯博士的实验室获得的数据引发的科学问题。他广泛的研究提供了一个独特的机会，可以对艾滋病毒感染者的神经认知障碍(NCI)的诊断和进展做出推断。然而，在这项研究中，大多数数据是以多模式大脑图像的形式出现的。因此，统计分析需要一种超越大规模单变量分析或简单回归方法的创新视角。对这些数据的分析需要创新的方法，通过将辅助的共同信息数据和临床知识结合在一起，用数学和分析框架全面地看待这些神经成像数据。该项目以四个目标应对这些挑战，重点是确定区分艾滋病毒感染患者和匹配的艾滋病毒阴性对照的成像标志物，并建立艾滋病毒感染者中NCI诊断和进展的特定生物标志物。在目标1中，我们确定哪些结构和功能的脑成像标记物区分HIV感染患者和匹配的HIV阴性对照。在目标2中，我们确定了哪些结构和功能成像标志物可以预测HIV感染患者的神经认知障碍(NCI)严重程度，而在目标3中，我们建立了预测未来NCI的成像生物标志物。目的4致力于阐明老龄化和HIV感染对NCI的存在和进展的协同作用。全球有3500万人感染艾滋病毒，其中40%以上患有神经或认知障碍。尽管提供了联合抗逆转录病毒疗法(CART)，但这些人面临大脑加速退化的风险，尽管疾病是通过无法检测到的病毒进行控制的。我们提出的方法直接解决了脑退行性变和随之而来的认知损害的研究，因此具有重大的临床和科学影响。所开发的方法广泛适用于各种复杂的数据设置。

 DESCRIPTION (provided by applicant): The study of neurocognitive impairment and its progression in HIV patients is a multifaceted endeavor involving complex data structures. These include multi-modal brain imaging measures as well as longitudinal host and viral markers. Exploring the full potential of these data requires the application and development of advanced statistical analysis methods. This proposal will address scientific questions motivated by the data obtained in Dr Ances' laboratory at Washington University in St. Louis. His extensive studies provide a unique opportunity to make inferences about the diagnosis and progression of neurocognitive impairment (NCI) among HIV-infected individuals. In this study, however, majority of the data is in the form of multi-modal brain images. Hence, the statistical analysis requires an innovative perspective that goes beyond mass univariate analyses or simple regression methods. Analysis of these data requires innovative methods which take a holistic view of these neuroimaging data with a mathematical and analytical framework that succeeds by incorporating adjunct co-informative data and clinical knowledge. This project answers these challenges with four aims focusing on determining imaging markers discriminating between HIV-infected patients and matched HIV-negative controls and establishing specific biomarkers of NCI diagnosis and progression among HIV-infected individuals. In Aim 1, we determine which structural and functional brain imaging markers discriminate between HIV- infected patients and matched HIV-negative controls. In Aim 2, we determine which structural and functional imaging markers predict neurocognitive impairment (NCI) severity in HIV-infected patients, whereas in Aim 3, we establish the imaging biomarkers predicting future NCI. Aim 4 is devoted to elucidating synergistic effects of aging and HIV infection on the NCI presence and progression. Thirty five million people worldwide are HIV-infected with over 40% having neurological or cognitive impairment. Despite the availability of combination antiretroviral therapy (cART), these individuals are at risk of accelerated brain degeneration, despite disease controlled in terms of undetectable virus. Our proposed methods directly address the study of brain degeneration and consequent cognitive impairment and thus have significant clinical and scientific impact. The developed methods are broadly applicable in a wide variety of complex data settings.