Multimodal Neuroimaging Approaches to Modeling Manganese Toxicity

项目总结/摘要 锰（Mn）是一种已知的神经毒素，成千上万的工人每天都暴露在其中，但它是 不知道目前的安全指南是适当的强大或太弱，以保护他们。在一个理想的世界里 了解一个人的接触史应有助于预测对健康影响的具体风险。到 监测锰焊接烟尘对工人的影响，医学成像技术，磁共振 成像（MRI）和光谱（MRS）用于对结构、功能和组织进行非侵入性成像。 人类大脑的神经化学然而，目前的研究并没有取得足够的进展， Mn暴露与MRI或MRS变化的关系。研究仅将Mn暴露与成像参数相关联 而不考虑金属的药代动力学特性或个体暴露史，因此 缺乏解释个体数据的能力。该项目的总体目标是填补这一关键空白， 创建和验证考虑成像数据、药代动力学特性 锰和个体暴露于锰，以预测毒性的个体效应。我们的组织正在进行一项， 对当地焊工和匹配对照的纵向神经影像学研究。我们将有丰富的， 脑MRI的纵向数据（例如，评估脑Mn负荷的T1图），几个脑MRI的MRS数据， 神经化学物质，包括GABA，来自个人空气采样和工作历史问卷的数据， 神经学和神经心理学测试结果，以及其他生物标志物（脚趾甲，血液）， 建模本项目的目的是评估和描述如何了解接触和 Mn的药代动力学特性使得能够将成像数据解释为定量脑Mn 沉积，以及大脑区域特异性锰沉积如何影响大脑其他区域的神经化学 从它被存放的地方。目的1寻求使用MRI结构成像和已知的药代动力学特性 以创建可以确定Mn沉积在特定区域中的量的数学模型。 大脑目的2探讨锰在脑内沉积的数量、持续时间和部位 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的变化， 随之而来的健康症状。重要的是，更好地解释个人成像数据也将告知 对工人个人的安全指导。

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.