Multimodal Neuroimaging Approaches to Modeling Manganese Toxicity

项目摘要/摘要 锰是一种已知的神经毒素，成千上万的工人每天都会接触到它，但它是 目前尚不清楚目前的安全指导方针是适当地强还是太弱，无法保护他们。在理想的世界里 了解个人的接触史应该能够预测对健康造成影响的具体风险。至 监测锰焊烟尘对作业工人的影响医学影像技术磁共振 成像(MRI)和波谱(MRS)用于非侵入性成像结构、功能和 人类大脑中的神经化学。然而，目前的研究并没有在连接方面取得足够的进展 锰暴露在MRI或MRS中的变化研究只是将锰暴露与成像参数相关联 而不考虑金属的药代动力学性质或个人暴露历史，因此 缺乏解释个别数据的能力。该项目的总体目标是通过以下方式填补这一关键空白 创建和验证考虑了成像数据、药动学特性 用来预测个体毒性效应的方法。我们的团队正在进行一项 本地电焊工和配对对照的纵向神经影像研究。因此，我们将拥有丰富的 脑MRI上的纵向数据(例如，用于评估脑MN负荷的T1图)，MRS数据上的几个 包括GABA在内的神经化学物质，来自个人空气采样和工作历史问卷的数据， 神经和神经心理测试结果，以及其他生物标记物(脚趾指甲，血液)供我们处理 模特儿。当前项目的目的是评估和描述关于接触和 锰的药代动力学特性使成像数据能够解释为定量的脑锰 沉积，以及大脑区域特定的锰沉积如何影响大脑其他区域的神经化学 从它存放的地方。目标1寻求使用核磁共振结构成像和已知的药代动力学特性 创建一个数学模型，该模型可以确定特定区域的锰沉积量 大脑。目的2研究大脑中锰沉积的数量、持续时间和位置。 会影响神经化学。这项研究的结果将是监测个人风险的第一步 通过提供必要的工具将暴露信息转化为大脑和 由此产生的健康症状。重要的是，对个别成像数据的更好解释也将有助于 工人个人的安全指南。

Project Summary/Abstract Manganese (Mn) is a known neurotoxin that tens of thousands of workers are exposed to daily, but it is unknown if the current safety guidelines are appropriately strong or too weak to protect them. In an ideal world knowledge of the exposure history of an individual should allow to predict specific risks for health effects. To monitor the effect of Mn welding fumes on workers, the medical imaging techniques Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) are used to non-invasively image the structure, function, and neurochemistry in the human brain. However, currently studies are not making adequate strides in connecting Mn exposure to changes in MRI or MRS. Studies are only correlating Mn exposure to imaging parameters without taking into account the pharmacokinetic properties of the metal or the individual exposure history, thus lacking the ability to interpret individual data. The broad objective of this project is to fill this crucial gap by creating and validating mathematical models that take into account imaging data, pharmacokinetic properties of Mn and the individual exposure to Mn to predict individual effects of toxicity. Our group runs an ongoing, longitudinal neuroimaging study on local welders and matched controls. Thus we will have abundant and longitudinal data on brain MRI (e.g. T1 maps to assess the brain Mn burden), MRS data on several neurochemicals including GABA, data from personal air sampling and work history questionnaires, neurological and neuropsychological test results, and other biomarkers (toe nails, blood) at our disposal for modeling. The purpose of the current project is to assess and describe how knowledge on exposure and pharmacokinetic properties of Mn enables the interpretation of imaging data as quantitative brain Mn deposition, and how brain-region specific Mn deposition affects neurochemistry in other regions of the brain from where it is deposited. Aim 1 seeks to use MRI structural imaging and known pharmacokinetic properties of Mn to create a mathematical model that can determine the amount of Mn deposition in specific regions of the brain. Aim 2 investigates how the amount, the duration, and the location of Mn deposition in the brain affects neurochemistry. The results of this study will be a first step towards monitoring of individual risks from Mn toxicity by providing the necessary tools to translate exposure information to changes in the brain and consequent health symptoms. Importantly, a better interpretation of individual imaging data will also inform safety guidelines for the individual worker.