Neuromelanin sensitive MRI as a novel, non-invasive index of dopamine function in adolescent-onset substance users

神经黑色素敏感 MRI 作为青少年吸毒者多巴胺功能的新型非侵入性指标

• 批准号: 9808805
• 负责人: Greg Perlman
• 金额: $ 19.94万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9808805
• 关键词: 11 year old; 16 year old; Adolescence; Adolescent; Adult; Age; Age of Onset; Alcohol consumption; Alcohol or Other Drugs use; Amphetamines; Anabolism; Archives; Biological Assay; Biological Markers; Childhood; Chronic; Corpus striatum structure; Cues; Data; Deposition; Development; Developmental Course; Diagnosis; Dimensions; Dopamine; Drug usage; Ensure; Factor Analysis; Female; Functional Magnetic Resonance Imaging; Gender; Goals; Health; Human; Intervention; Interview; Investigation; Link; Longevity; Magnetic Resonance Imaging; Measures; Methods; Neurons; Pathway interactions; Pattern; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Prevention; Prospective Studies; Proxy; Raclopride; Radiation exposure; Recording of previous events; Recovery; Reporting; Research; Rewards; Risk; Sampling; Schedule; Signal Transduction; Source; Structure; Substance Use Disorder; Substantia nigra structure; Technology; Test Result; Testing; Time; Translational Research; Universities; Validation; Visit; Woman; Youth; addiction; adolescent drug use; adolescent substance use; age group; base; clinically significant; cohort; cost; demographics; gender difference; high risk; imaging biomarker; imaging modality; imaging study; in vivo; indexing; male; men; neuromelanin; nicotine use; novel; novel marker; opioid use disorder; prospective; recruit; stimulant use; tool; transmission process; young adult

PROJECT SUMMARY/ ABSTRACT Chronic drug use is associated with low levels of dopamine release in the striatum. Despite the importance to translational science, the developmental course of low dopamine function is unknown. For instance, it is fundamentally unclear in humans whether low dopamine function precedes or follows from substance use, if rate of divergence in substance-exposed youth is slow or rapid, or if there are differential effects by gender or by pattern of substance use. The primary obstacles are that 1.) Positron Emission Tomography (PET) imaging cannot be utilized in pediatric populations to track early changes in dopamine function, and 2.) there is no developmentally-appropriate alternative imaging method. Translational science awaits a valid index of a dopamine-related biosynthesis pathway for assessing normal developmental trajectories in youth, as well as deviation before, during, and after onset of substance use. Recently, we found that a neuromelanin-sensitive magnetic resonance imaging (NM-MRI) sequence yields a direct index of dopamine release in the striatum. Unlike PET imaging, NM-MRI does not involve radiation exposure and is appropriate for pediatric populations. We have also observed that NM-MRI signal is detected as early as 11 years of age. This R21 application proposes to collect NM-MRI in 160 20-22 year-olds, an age group that is transitioning from adolescence to adulthood. Our aim is to establish a definitive link between NM-MRI level and total lifetime substance use. Total lifetime substance use will be carefully assessed by semi-structured interview and quantified dimensionally using factor analysis. We will also explore gender differences and identify if specific aspects of substance use differentially impact NM-MRI level over and above total exposure (e.g., age of onset). The women will be recruited from an existing cohort allowing us to test the link using prospective (archival), as well as retrospective (newly collected), substance use data. The men will be newly recruited and allow for a test of gender differences. Positive results will be novel evidence of a link between early-course dopaminergic disturbance and adolescent-onset substance use. This would support use of NM- MRI to describe synergistic links between dopamine function and adolescent substance use prospectively in a new pediatric study. Indeed, NM-MRI is a promising new tool for dopamine research where PET imaging is not feasible due cost, access to facilities, health risk, or age of sample.

项目摘要/摘要 慢性药物使用与纹状体中多巴胺释放较低有关。尽管有 对于转化科学的重要性，低多巴胺功能的发展过程尚不清楚。为了 实例，在人类中，从根本上不清楚多巴胺功能先于还是从 药物使用，如果暴露于物质的青年的差异速度很慢或很快，或者如果有差异 性别或物质使用模式的影响。主要障碍是1.）正电子发射 层析成像（PET）成像不能在儿科种群中用于跟踪多巴胺的早期变化 功能，2。）没有适当的替代成像方法。翻译科学 等待与多巴胺相关的生物合成途径的有效索引，以评估正常发育 青年的轨迹以及在使用物质发作之前，期间和之后的偏差。最近，我们发现 神经苯胺敏感的磁共振成像（NM-MRI）序列产生的直接指数 多巴胺在纹状体中释放。与PET成像不同，NM-MRI不涉及辐射暴露，IS 适合小儿种群。我们还观察到NM-MRI信号早在11时被检测到 年龄。此R21申请建议收集160 20-22岁的NM-MRI，一个年龄段 从青春期过渡到成年。我们的目的是在NM-MRI级别和 总终身药物使用。终身用品的总使用将通过半结构化仔细评估 使用因子分析在尺寸上进行访谈和量化。我们还将探索性别差异和 确定使用物质的特定方面是否会差异地影响NM-MRI的水平，而不是全面暴露 （例如，发病年龄）。这些妇女将从现有队列中招募，使我们可以使用 潜在的（档案）以及回顾性（新收集），物质使用数据。男人将是新的 招募并允许测试性别差异。积极的结果将是新的证据证明 早期的多巴胺能障碍和青少年发作的药物使用。这将支持使用NM- MRI描述多巴胺功能与青少年物质之间使用的协同联系 新的儿科研究。确实，NM-MRI是多巴胺研究的有前途的新工具，其中宠物成像不是 可行的应有成本，获取设施，健康风险或样本年龄。