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

项目摘要 尽管广泛使用抗逆转录病毒疗法，但在120万携带艾滋病毒的美国人中，近一半 经历神经认知障碍(NCI)，对日常功能产生负面影响。与HIV相关的NCI是 估计是全球最常见的中年NCI形式。滥用药物是一种非常普遍的共病 艾滋病毒携带者会增加与艾滋病毒相关的非传染性疾病的风险。单峰核磁共振研究表明，艾滋病毒和药物 虐待都与大脑中一系列不同的结构和功能变化有关，但它们是如何 互动还没有被很好地理解。传统的单峰分析在其表征能力方面是有限的 复杂的神经精神疾病，因为每一种模式都提供了对大脑的不完整看法。在……里面 相比之下，我们建议使用创新的融合方法，利用多模式数据的丰富性来 同时发现多种神经成像方式和认知测量之间的协变。这 Proposal利用了来自NIDA资助的3个已完成项目的现有数据，这些数据涉及 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个艾滋病毒阳性病例和109个艾滋病毒阴性病例) 有深入的物质使用史，多模式脑成像(即结构、扩散和静息状态 功能磁共振成像)，全面的神经认知电池，以及广泛的其他表型数据。这个 中心假设是HIV特异性灰质体积和白质完整性形状的共同变化 神经功能，进而NCI，而可卡因的使用由于其长期影响而恶化这些改变 在神经回路上。利用互补的多模式分析(监督融合和连接学)，我们的目标是 以：(1)确定HIV神经系统疾病和相关的NCI的神经生物标记物；和(2)将可卡因作为一种 HIV特异性大脑结构和功能改变及相关NCI的协调者。此外， 该项目将开发新的、先进的方法来提高MRI数据质量，以实现交叉研究的协调，并 优化基于多峰指数的NCI预测。此合并数据集提供了一个 史无前例的机会来测试关于HIV神经基质的新的和临床上重要的假说- 在药物滥用的背景下与NCI相关联。这项提议直接回应了研究的需要 “描述由于长期吸毒而导致的大脑形态或功能的异常”和“[ITS 在艾滋病毒/艾滋病的发病、治疗、预防和服务提供的演变动态中的作用“[PAR- 16-234]。这项研究还涉及艾滋病指定资助的高优先主题，包括调查 神经系统并发症[非-15-137]。建立在健全的前提和稳健的初步数据基础上，这 创新项目有很强的潜力来确定合适的神经艾滋病毒生物标志物，这可能会促进 积极吸毒者的诊断和治疗监测，并作为临床干预的目标 减轻艾滋病毒相关非传染性疾病造成的负担。

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.