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

项目摘要/摘要 长期吸毒与纹状体中低水平的多巴胺释放有关。尽管 对于翻译科学的重要性，低多巴胺功能的发展过程尚不清楚。为 例如，在人类中，基本上还不清楚低多巴胺功能是先于还是之后于 物质使用，如果接触物质的年轻人发散速度慢或快，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 体层摄影术(PET)不能在儿科人群中用来追踪多巴胺的早期变化 函数，以及2.)目前还没有适合发育的替代成像方法。翻译科学 等待评估正常发育的多巴胺相关生物合成途径的有效指标 青少年的运动轨迹，以及在开始使用药物之前、期间和之后的偏差。最近，我们发现 神经黑色素敏感的磁共振成像(NM-MRI)序列产生了 纹状体中的多巴胺释放。与PET成像不同，NM-MRI不涉及辐射暴露， 适用于儿科人群。我们还观察到早在11点就检测到了NM-MRI信号 几年前。这个R21应用程序建议在160名20-22岁的年轻人中收集NM-MRI，这个年龄段是 从青春期过渡到成年期。我们的目标是建立NM-MRI水平和NM-MRI水平之间的明确联系 终生物质使用总量。将通过半结构化方法仔细评估整个生命周期的物质使用情况 访谈采用因子分析进行维度量化。我们还将探讨性别差异和 确定物质使用的特定方面是否会对总暴露以上的NM-MRI水平产生不同影响 (例如，发病年龄)。这些女性将从现有的队列中招募，允许我们使用 预期(档案)以及追溯性(新收集)的物质使用数据。这些人将会是新来的 招聘，并允许对性别差异进行测试。积极的结果将是新的证据，证明 早期多巴胺能障碍和青春期药物使用。这将支持使用NM- MRI用于前瞻性描述多巴胺功能和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是一种很有前途的新工具，用于研究多巴胺，而PET成像不能 可行的应有成本、设施使用情况、健康风险或样品年龄。

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.