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.

项目摘要 尽管抗逆转录病毒疗法被广泛使用，但120万美国艾滋病毒感染者中有近一半 神经认知障碍（NCI）对日常功能产生负面影响。HIV相关的NCI是 估计是世界范围内中年NCI最常见的形式。药物滥用是一种高度流行的合并症， HIV阳性者，增加HIV相关NCI的风险。单峰MRI研究表明，艾滋病毒和药物 每一种虐待都与大脑中一系列不同的结构和功能改变有关，但它们是如何改变的呢？ 交互作用还没有被很好地理解。传统的单模分析在表征能力方面受到限制 复杂的神经精神疾病，因为每一种模式都提供了一个不完整的大脑视图。在 相比之下，我们建议使用创新的融合方法，利用丰富的多模态数据， 同时发现多种神经成像方式和认知测量的协变。这 一项提案利用了来自3个已完成的NIDA资助项目的现有数据，这些项目是关于 艾滋病毒和药物滥用。合并后，数据集将包括217个独特病例（108个HIV+和109个HIV-） 利用深入的物质使用历史，多模态脑图像（即，结构、扩散和静止状态 功能性磁共振成像），全面的神经认知电池，以及广泛的其他表型数据。的 中心假设是，在灰质体积和白色物质完整性形状中的HIV特异性共同改变 神经功能，进而NCI，可卡因使用由于其长期影响而使这些改变消失 神经回路使用互补的多模态分析（监督融合和连接组学），我们的目标是 目的：（1）鉴定HIV神经系统疾病和相关NCI的神经生物标志物;（2）测试可卡因作为一种抗病毒药物。 HIV特异性脑结构和功能的共同改变以及相关的NCI的调节剂。此外该 该项目将开发新的先进方法，以提高MRI数据质量，实现跨研究协调， 优化基于多模态指数的NCI预测。这个合并的数据集提供了一个 前所未有的机会来测试有关艾滋病毒神经基质的新的和临床重要的假设- 在药物滥用的背景下，与NCI相关。该提案直接回应了研究的需要， “描述由于长期吸毒而导致的异常脑形态或功能”和“[其 作用]在艾滋病毒/艾滋病发病机制、治疗、预防和服务提供的不断变化的动态中”[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]。基于一个良好的前提和可靠的初步数据， 创新项目有很大潜力来确定适当的神经HIV的神经生物标志物， 积极吸毒者的诊断和治疗监测，并作为临床干预措施的目标， 减轻HIV相关NCI造成的负担。