Development and Validation of a Novel In Vivo Neutron Activation Analysis Technol

新型体内中子活化分析技术的开发和验证

• 批准号: 8303563
• 负责人: Linda H Nie
• 金额: $ 23.22万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303563
• 关键词: Development; Validation; Novel; Vivo; Neutron

DESCRIPTION (provided by applicant): Millions of workers, including over 500,000 welders employed in the United States, have been exposed to excessive metals. Human and animal studies have strongly linked metal exposure to neurophysiological disorders and neurodegenerative diseases. Manganese (Mn) is one of the most significant metal neuro- toxicants among workers. Many occupational studies have documented Mn toxicity. However, the threshold of Mn exposure, the mechanism of the toxicity of Mn, and the interaction of Mn with other metals (such as lead and mercury) are unknown and therefore deserve further investigation. One pending issue in assessment of Mn exposure pertains to the selection of proper biomarker. Over 40% of Mn in human body is stored in bone, which renders bone Mn to be the ideal biomarkers to assess cumulative Mn in the body with long-term, low dose exposure, a pattern typically seen among workers occupationally exposed to Mn. In this project, a novel neutron activation analysis technology will be developed to noninvasively quantify Mn in bone in vivo. Later we will apply this technology in a larger project to study the possible synergistic neurotoxic effect of the exposure of metal mixtures among worker populations. Our central hypothesis to be tested in this proposal is that a novel transportable neutron activation analysis technology can be developed and validated for non invasive in vivo quantification of Mn in bone. We will conduct a series of Monte Carlo simulations to select the best design of the system, set up the system based on the chosen design, optimize the design with experiments, and develop new algorithms to analyze the data and calibrate the system. At the completion of this project, a novel technology for cumulative Mn exposure assessment will be established. The new technology and knowledge will help to fill the data gaps regarding appropriate individual exposure assessment of metals and to provide valuable information on early diagnose of Mn exposure and toxicity. The use of new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two main reasons. First, neurophysiological disorder is one of the main health issues for these workers; second, neurological impairment reduces the workers' productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page PUBLIC HEALTH RELEVANCE: The proposed research is relevant to occupation health because it addresses a critical problem regarding the development and validation of a novel technology to assess cumulative exposure to one of the most significant metal neuro-toxicants, manganese, among workers. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

描述（由申请人提供）：美国有数百万工人，包括超过 500,000 名焊工，接触过过量的金属。人类和动物研究表明，金属暴露与神经生理障碍和神经退行性疾病密切相关。锰 (Mn) 是对工人最重要的金属神经毒物之一。许多职业研究都记录了锰的毒性。然而，锰暴露的阈值、锰的毒性机制以及锰与其他金属（如铅和汞）的相互作用尚不清楚，因此值得进一步研究。锰暴露评估中的一个悬而未决的问题涉及选择适当的生物标志物。人体内超过 40% 的锰储存在骨骼中，这使得骨锰成为评估长期、低剂量接触体内锰累积情况的理想生物标志物，这种模式通常出现在职业接触锰的工人中。在该项目中，将开发一种新型中子活化分析技术，以无创地量化体内骨骼中的锰。稍后我们将在一个更大的项目中应用这项技术，以研究工人群体中接触金属混合物可能产生的协同神经毒性效应。我们在本提案中要测试的中心假设是，可以开发并验证一种新型可传输中子活化分析技术，用于骨中锰的无创体内定量。我们将进行一系列蒙特卡洛模拟来选择系统的最佳设计，根据所选设计建立系统，通过实验优化设计，并开发新算法来分析数据和校准系统。该项目完成后，将建立一种累积锰暴露评估的新技术。新技术和知识将有助于填补有关适当的个人金属暴露评估的数据空白，并为锰暴露和毒性的早期诊断提供有价值的信息。使用新的生物标志物来了解接触锰的神经毒性作用对于数百万接触锰的工人至关重要，主要原因有两个。首先，神经生理障碍是这些工人的主要健康问题之一；其次，神经功能障碍会降低工人的生产力，是工伤的主要原因。 PHS 398/2590（修订版 06/09） 页面延续 格式页面 公共健康相关性：拟议的研究与职业健康相关，因为它解决了有关新技术开发和验证的关键问题，以评估工人对最重要的金属神经毒物之一锰的累积暴露量。 PHS 398/2590（修订版 06/09） 页面延续 格式页面