MRI data fusion to investigate effects of drug abuse on HIV neurological complications

MRI 数据融合研究药物滥用对 HIV 神经并发症的影响

• 批准号: 10347306
• 负责人: CHRISTINA S MEADE
• 金额: $ 14.17万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10347306
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adult; Affect; American; Arizona; Biological; Biological Factors; Biological Markers; Brain; Brain imaging; Chronic; Clinical; Cocaine; Cocaine use disorder; Cognitive; Collaborations; Complex; Computer software; Corpus striatum structure; Data; Data Set; Databases; Diagnosis; Diffusion; Disease Progression; Drug Use Disorder; Drug abuse; Drug usage; Drug user; Enrollment; Functional Magnetic Resonance Imaging; Funding; Goals; HIV; HIV-associated neurocognitive disorder; Hybrids; Individual; Intervention; Investigation; Joints; Link; Long-Term Effects; Longevity; Machine Learning; Magnetic Resonance Imaging; Measures; Medical Records; Methodology; Methods; Mind-Body Method; Modality; Modeling; Monitor; Morphologic artifacts; National Institute of Drug Abuse; Neurocognitive; Neurocognitive Deficit; Neurologic; Neurophysiology - biologic function; Neurosciences; Pathogenesis; Patients; Pattern; Persons; Pharmaceutical Preparations; Prevalence; Recording of previous events; Research; Rest; Rewards; Risk; Role; Sampling; Scanning; Severities; Shapes; Stimulant; Structure; Supervision; Techniques; Testing; Universities; antiretroviral therapy; base; brain morphology; cocaine use; comorbidity; comparison group; connectome data; daily functioning; data fusion; data harmonization; data quality; denoising; executive function; experience; frontal lobe; gray matter; improved; indexing; innovation; middle age; multimodal data; multimodality; nervous system disorder; neural circuit; neuroAIDS; neurobehavioral; neuroimaging; neuropsychiatric disorder; non-drug; phenotypic data; predictive marker; predictive modeling; prevention service; public health relevance; relating to nervous system; service delivery; sound; stimulant use; substance use; white matter

Project Summary Despite widespread use of antiretroviral therapy, nearly half of the 1.2 million Americans living with HIV experience neurocognitive impairments (NCI) that negatively impact daily functioning. HIV-associated NCI is estimated to be the most common form of midlife NCI worldwide. Drug abuse, a highly prevalent comorbidity in HIV+ persons, increases the risk of HIV-associated NCI. Unimodal MRI studies have shown that HIV and drug abuse are each linked with a distinct set of structural and functional alterations in the brain, but how they interact is not well understood. Conventional unimodal analyses are limited in their ability to characterize complex neuropsychiatric diseases because each modality provides an incomplete view of the brain. In contrast, we propose to use innovative fusion approaches that exploit the richness of multimodal data to discover covariations across multiple neuroimaging modalities and cognitive measures simultaneously. This proposal capitalizes on existing data from 3 completed NIDA-funded projects on the neurobehavioral effects of HIV and drug abuse. When combined, the dataset will consist of 217 unique cases (108 HIV+ and 109 HIV-) with in-depth substance use histories, multimodal brain images (i.e., structural, diffusion, and resting-state functional MRI), comprehensive neurocognitive batteries, and a wide range of other phenotypic data. The central hypothesis is that HIV-specific co-alterations in gray matter volume and white matter integrity shape neural functioning and in turn NCI, and that cocaine use worsens these alterations due to its long-term effects on neural circuitry. Using complementary multimodal analyses (supervised fusion and connectomics), we aim to: (1) identify neural biomarkers of HIV neurological disease and associated NCI; and (2) test cocaine as a moderator of HIV-specific co-alterations in brain structure and function and associated NCI. In addition, the project will develop new, advanced methods to improve MRI data quality for cross-study harmonization and to optimize the prediction of NCI based on multimodal indices. This amalgamated dataset provides an unprecedented opportunity to test new and clinically important hypotheses about the neural substrates of HIV- associated NCI in the context of drug abuse. The proposal responds directly to the need for research to “characterize brain morphology or function that is aberrant as a consequence of chronic drug use” and “[its role] in the evolving dynamics of HIV/AIDS pathogenesis, treatment, prevention, and service delivery” [PAR- 16-234]. This research also addresses high priority topics for AIDS-designated funding, including investigation of neurological complications [NOT-15-137]. Building upon a sound premise and robust preliminary data, this innovative project has strong potential to identify appropriate neural biomarkers of neuroHIV that may facilitate diagnosis and treatment monitoring in active drug users and serve as targets for clinical interventions to mitigate the burden caused by HIV-associated NCI.

项目概要 尽管抗逆转录病毒疗法得到广泛使用，但 120 万美国人中近一半的艾滋病毒感染者 经历对日常功能产生负面影响的神经认知障碍 (NCI)。 HIV 相关 NCI 是 据估计是全球最常见的中年 NCI 形式。药物滥用是一种非常普遍的合并症 HIV+ 人群会增加 HIV 相关 NCI 的风险。单模态 MRI 研究表明，HIV 和药物 每种虐待都与大脑中一组独特的结构和功能改变有关，但它们是如何发生的 交互不是很好理解。传统的单峰分析的表征能力有限 复杂的神经精神疾病，因为每种方式提供的大脑视图都是不完整的。在 相比之下，我们建议使用创新的融合方法，利用多模态数据的丰富性 同时发现多种神经影像模式和认知测量之间的协变。这 该提案利用了 3 个已完成的 NIDA 资助项目的现有数据，这些项目涉及神经行为影响 艾滋病毒和药物滥用。合并后，数据集将包含 217 个独特病例（108 个 HIV+ 和 109 个 HIV-） 具有深入的物质使用历史、多模式大脑图像（即结构、扩散和静息态） 功能性 MRI）、全面的神经认知电池以及广泛的其他表型数据。这 中心假设是，灰质体积和白质完整性形状中的艾滋病毒特异性共同改变 神经功能和 NCI，而可卡因的长期影响会加剧这些变化 关于神经回路。使用互补的多模式分析（监督融合和连接组学），我们的目标是 (1) 识别 HIV 神经系统疾病和相关 NCI 的神经生物标志物； (2) 测试可卡因作为 HIV 特异性大脑结构和功能共同改变以及相关 NCI 的调节剂。此外， 项目将开发新的先进方法来提高 MRI 数据质量，以实现交叉研究协调并 基于多模态指数优化NCI预测。该合并数据集提供了 这是一个前所未有的机会来测试关于 HIV 神经基质的新的、临床上重要的假设。 与药物滥用相关的 NCI。该提案直接响应了研究的需要 “描述由于长期吸毒而导致的大脑形态或功能异常”和“[其 在艾滋病毒/艾滋病发病机制、治疗、预防和服务提供的动态演变中的作用]”[PAR- 16-234]。这项研究还涉及艾滋病指定资金的高度优先主题，包括调查 神经系统并发症 [NOT-15-137]。建立在合理的前提和可靠的初步数据的基础上， 创新项目具有识别神经艾滋病毒适当神经生物标志物的巨大潜力，这可能有助于 对活跃吸毒者进行诊断和治疗监测，并作为临床干预的目标 减轻 HIV 相关 NCI 造成的负担。