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.

项目概要/摘要 长期吸毒与纹状体中多巴胺释放水平低有关。尽管 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 例如，对于人类来说，根本不清楚多巴胺功能低下是先于还是后于 物质使用，如果接触物质的青少年的差异率是缓慢或快速，或者是否存在差异 性别或物质使用模式的影响。主要障碍是 1.) 正电子发射 断层扫描 (PET) 成像不能用于儿科人群来追踪多巴胺的早期变化 功能，以及 2.) 没有适合发育的替代成像方法。转化科学 等待多巴胺相关生物合成途径的有效指标来评估正常发育 青少年时期的轨迹，以及物质使用开始之前、期间和之后的偏差。最近，我们发现 神经黑色素敏感磁共振成像 (NM-MRI) 序列可产生直接指数 纹状体释放多巴胺。与 PET 成像不同，NM-MRI 不涉及辐射暴露，并且 适合儿科人群。我们还观察到，NM-MRI 信号早在 11 点就被检测到。 岁数。该 R21 应用程序建议收集 160 名 20-22 岁人群的 NM-MRI，该年龄组为 从青春期过渡到成年。我们的目标是在 NM-MRI 水平和 终生物质使用总量。终生物质使用量将由半结构化机构仔细评估 访谈并使用因子分析进行维度量化。我们还将探讨性别差异 确定物质使用的特定方面是否对 NM-MRI 水平产生超过总暴露量的差异影响 （例如发病年龄）。这些女性将从现有队列中招募，使我们能够使用以下方法测试这种联系： 前瞻性（档案）以及回顾性（新收集的）物质使用数据。男人们将焕然一新 招募并允许测试性别差异。积极的结果将成为证明两者之间存在联系的新证据 早期多巴胺能紊乱和青少年发病的物质使用。这将支持使用 NM- MRI 前瞻性地描述多巴胺功能与青少年物质使用之间的协同联系 新的儿科研究。事实上，NM-MRI 是一种有前途的多巴胺研究新工具，而 PET 成像则无法做到这一点。 由于成本、设施的使用、健康风险或样本年龄而可行。