Validation of Portable XRF for In Vivo Measurement of Heavy Metal Exposures

描述(由申请人提供)：我们建议使用一种新的便携式X射线荧光(XRF)设备来验证用于人体金属活体分析的方法。目前，在流行病学健康研究中，骨中铅和脚趾甲中几种金属的浓度被用来评估长期接触这些金属的情况。虽然这些生物标志物提供了宝贵的暴露数据，这些数据在许多金属暴露的健康研究中被证明是非常有用的，但它们也有缺陷，可能会限制它们的用途，并可能产生偏差结果。其中最主要的是对研究性研究对象的可接受性，这可能会限制参与者的数量，从而降低检测关联的能力(在某些情况下，还会使研究完全不可行)，并可能根据谁同意参与而对结果产生偏差。传统的骨铅分析方法--CD109KXRF--要求参与者来到一个中心研究地点，静坐至少半个小时。这可能会给许多人带来负担，对于一些患者群体，例如痴呆症患者，这使得研究基本上是不可能的。此外，有关使用放射性镉109源的监管要求限制了具有这一能力的研究小组的数量。测量脚趾甲中的金属要求研究对象有足够的脚趾甲长度来获得修剪， 这可能会限制参与，但此外，一些人发现提供脚趾甲修剪是不可接受的，使他们无法进行研究。我们的新方法包括使用便携式XRF设备进行测量，可以在几分钟内完成，对完整的组织进行非侵入性测量。这些优势将消除当前传统方法的问题，从而导致对金属暴露对健康影响的研究的极大扩展，打开了在有特殊需要的地点对金属进行人类健康研究的可能性，并通过提供金属中毒的实时现场诊断来帮助指导与金属暴露有关的公共卫生预防工作。在我们研究的初始阶段，我们将把骨骼中的铅和脚趾甲中的汞(Hg)和锰(Mn)的分析与目前最先进的测量方法进行比较。根据我们的新方法满足验证和可行性标准，我们将在芝加哥健康和老龄化项目的大型、基于人口的不同种族老年人研究队列的背景下，评估与认知能力下降有关的这三种金属的暴露。我们将比较基于XRF的骨铅测量结果和基于职业史的铅暴露，这是一种常见的、尽管远不理想的长期暴露数据来源，在大型成人研究中。

DESCRIPTION (provided by applicant): We propose to validate approaches using a novel portable X-ray fluorescence (XRF) device for the in vivo analysis of metals in humans. Concentrations of lead (Pb) in bone and several metals in toenails are currently used to assess long-term exposures to these metals in epidemiological health research. While these biomarkers provide valuable exposure data that has proved extremely useful in many health studies of metal exposure, they have drawbacks that can limit their utility and possibly bias results obtained. Chief among these is acceptability to research study subjects, which can limit the number of participants, and as a result reduce the power to detect associations (and in some cases make studies completely unfeasible) and potentially bias results depending on who agrees to participate. The conventional approach to bone Pb analyses-Cd109 KXRF-requires participants to come to a central study site and sit still for at least one half hour. This can be burden to many, and for some patient populations, e.g. patients with dementia, make a study essentially impossible. In addition, regulatory requirements around the use of the radioactive Cd109 source have limited the number of research groups with this capability. Measuring metals in toenails requires that study subjects have sufficient toenail length to obtain clippings, which can limit participation, but furthermore, some populations find providing toenail clippings unacceptable, making research among them impossible. Our new approach involves measurements with a portable XRF device and can be done in a matter of minutes, non-invasively on intact tissue. These advantages will obviate the problems with the current conventional approaches, thereby resulting in a tremendous expansion of research into health effects of metal exposures, opening up the possibility of human health research on metals at sites of particular need, and helping direct public health exposure prevention efforts related to metal exposures by providing real-time on-site diagnosis of metal intoxication. In the initial phase of our study, we will compare the analysis of Pb in bone and mercury (Hg) and manganese (Mn) in toenails with the current state-of-the-art measurement approaches. Contingent on our new approach meeting validation and feasibility criteria, we will evaluate exposures to these three metals in relation to cognitive decline within the context of a large, established population-based research cohort of ethnically diverse elderly adults, the Chicago Health and Aging Project. We will compare findings using the XRF-based measurement of bone Pb with Pb exposure based on occupational history, a commonly available, though far from ideal, source of long-term exposure data in large studies of adults.