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

描述（由申请人提供）：我们建议使用新型便携式X射线荧光（XRF）设备对人体金属体内分析方法进行验证。在流行病学健康研究中，目前使用骨中铅（Pb）和脚趾甲中几种金属的浓度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有价值的暴露数据，在许多金属暴露的健康研究中证明是非常有用的，但它们有缺点，可能会限制它们的实用性，并可能使获得的结果产生偏差。其中最主要的是研究对象的可接受性，这可能会限制参与者的数量，从而降低检测相关性的能力（在某些情况下，使研究完全不可行），并可能根据谁同意参与而产生偏倚结果。骨铅分析的传统方法-Cd 109 KXRF-要求参与者来到中心研究地点，静坐至少半小时。这对许多人来说可能是负担，并且对于一些患者群体，例如痴呆患者，使研究基本上不可能。此外，围绕放射性Cd 109源的使用的监管要求限制了具有这种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具有足够的脚趾甲长度以获得剪下的指甲， 这可能会限制参与，但此外，有些人认为提供脚趾甲剪是不可接受的，使他们之间的研究成为不可能。我们的新方法涉及使用便携式XRF设备进行测量，可以在几分钟内完成，对完整组织无创。这些优点将解决目前传统方法的问题，从而极大地扩展了对金属暴露对健康影响的研究，开辟了在特别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，帮助直接进行与金属暴露有关的公共卫生暴露预防工作。在我们研究的初始阶段，我们将比较分析铅在骨骼和汞（汞）和锰（锰）在脚趾甲与当前国家的最先进的测量方法。视我们的新方法符合验证和可行性标准而定，我们将在一个大型的、已建立的基于人群的研究队列（芝加哥健康与老龄化项目）的背景下，评估这三种金属与认知能力下降的关系。我们将比较结果使用基于X射线荧光光谱测量骨铅与铅暴露的职业史的基础上，一个常见的，但远不理想的，长期暴露的数据来源，在大型研究的成年人。

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.