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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要尽管使用了抗逆转录病毒疗法的宽度，但在120万美国人中，几乎一半体验神经认知障碍（NCI），对日常功能产生负面影响。 HIV相关的NCI是据估计是全球中年NCI的最常见形式。药物滥用，高度普遍的合并症艾滋病毒+人增加了与HIV相关的NCI的风险。单峰MRI研究表明艾滋病毒和药物滥用都与大脑中的一系列结构和功能变化相关联，但它们如何互动不太了解。传统的非峰分析的表征能力有限复杂的神经精神疾病是因为每种方式都提供了对大脑的不完整视图。在对比，我们建议使用创新的融合方法来利用多模式数据的丰富性简单地发现多种神经影像模式和认知措施的协变量。这提案从3个已完成的NIDA资助的项目中利用现有数据，以实现神经行为影响艾滋病毒和吸毒。合并后，该数据集将由217个唯一情况（108 HIV+和109 HIV-）组成。具有深入的物质使用历史，多模式的大脑图像（即结构，扩散和静止状态功能性MRI），全面的神经认知电池和其他表型数据。中心假设是HIV特异性的共同变化灰质体积和白质完整性形状神经功能和NCI反过来，并且可卡因的使用使这些改变因其长期影响而恶化在神经电路上。使用完整的多模式分析（有监督的融合和连接组），我们的目标至：（1）确定HIV神经疾病和相关NCI的神经元生物标志物；（2）可卡因作为一个 HIV特异性共同转化的主持人在大脑结构和功能以及相关的NCI中。另外，项目将开发新的高级方法，以提高MRI数据质量以进行跨研究和协调基于多模式指数优化NCI的预测。此合并数据集提供了前所未有的机会来检验有关HIV的神经底物的新的和临床上重要的假设在吸毒的背景下相关的NCI。该提案直接回应了研究的需求 “特征脑形态或功能是由于长期使用而异常的”和“ 在HIV/AIDS发病机理，治疗，预防和服务递送的演化动力学中的作用] 16-234]。这项研究还涉及艾滋病指定资金的高优先级主题，包括调查神经系统并发症[非15-137]。以合理的前提和强大的初步数据为基础创新项目具有巨大的潜力，可以识别可能有助于促进的神经凝血的合适的神经虫标志物活跃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与HIV相关的NCI引起的燃烧。