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

HIV相关认知能力下降的多模式脑成像研究统计模型

• 批准号: 8993065
• 负责人: Jaroslaw Harezlak
• 金额: $ 42.16万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-03 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8993065
• 关键词: Address; Adopted; Advanced Development; Aging; Anti-Retroviral Agents; Area; Biological Markers; Blood; Brain; Brain imaging; CD4 Lymphocyte Count; Cerebrum; Clinical; Clinical Data; Complex; Core-Binding Factor; Data; Data Analyses; Data Set; Dependence; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease Progression; Epidemiology; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Goals; HIV; HIV Infections; HIV Seropositivity; HIV-associated neurocognitive disorder; Health; Image; Imaging technology; Impaired cognition; Impairment; Individual; Joints; Knowledge; Laboratories; Life; Magnetic Resonance Imaging; Measures; Medical; Methods; Modeling; Neurocognitive Deficit; Neurologic; Patients; Plasma; Play; Public Health; RNA; Research; Rest; Risk; Role; Severities; Software Tools; Spin Labels; Statistical Methods; Statistical Models; Structure; Test Result; Testing; Thick; Universities; Viral Markers; Virus; Washington; age effect; analytical method; antiretroviral therapy; cognitive change; cohort; disorder control; imaging biomarker; immunological status; improved; innovation; neuroimaging; neuropsychological; novel; public health relevance

 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.

 描述（由申请人提供）： HIV 患者的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工作。这些包括多模式脑成像测量以及纵向宿主和病毒标记。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。该提案将解决由圣路易斯华盛顿大学安塞斯博士实验室获得的数据引发的科学问题。他的广泛研究提供了一个独特的机会来推断 HIV 感染者神经认知障碍 (NCI) 的诊断和进展。然而，在这项研究中，大部分数据都是多模态大脑图像的形式。因此，统计分析需要超越大规模单变量分析或简单回归方法的创新视角。这些数据的分析需要创新的方法，通过数学和分析框架对这些神经影像数据进行整体观察，并通过结合辅助信息数据和临床知识来取得成功。该项目通过四个目标来应对这些挑战，重点是确定区分 HIV 感染者和匹配的 HIV 阴性对照的成像标记物，并建立 HIV 感染者中 NCI 诊断和进展的特定生物标记物。在目标 1 中，我们确定哪些结构和功能脑成像标记可以区分 HIV 感染患者和匹配的 HIV 阴性对照。在目标 2 中，我们确定哪些结构和功能成像标记物可以预测 HIV 感染者的神经认知障碍 (NCI) 严重程度，而在目标 3 中，我们建立了预测未来 NCI 的成像生物标记物。目标 4 致力于阐明衰老和 HIV 感染对 NCI 存在和进展的协同影响。全球有 3500 万人感染艾滋病毒，其中超过 40% 的人患有神经或认知障碍。尽管可以使用联合抗逆转录病毒疗法（cART），但这些人仍面临着大脑加速退化的风险，尽管疾病已被无法检测到的病毒所控制。我们提出的方法直接针对大脑退化和随之而来的认知障碍的研究，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。