Rapid Radiation Dose Estimation

说明(申请人提供)：人类暴露在辐射中，无论是意外使用还是故意使用，都有可能影响大量人口，并对授权应对此类事件的设施和资源造成严重负担。目前，辐射暴露的临床管理缺乏快速和可靠地提供相关的人体剂量估计的能力。这些信息对于临床医生就可能暴露在危险水平的辐射中的患者的治疗做出明智的决定至关重要。因此，许多机构高度重视开发用于分诊情况的新的辐射生物剂量测定方法。这项建议描述了对一种新的血液毒性反应矩阵(HAME)的进一步评估，该矩阵将提供可用于估计剂量的辐射诱导的造血系统损害的多参数评估。该分析基于对全血细胞群体的询问，以了解存在的细胞数量和这些细胞的健康状况的变化。这是通过使用流式细胞仪对细胞进行计数并测量作为细胞凋亡指标的线粒体膜电位的变化来实现的。初步实验表明，伤害分析是快速、微创、廉价的，并有可能区分临床相关的辐射剂量。本提案中描述的实验将提供关于该分析满足功能性人体辐射生物剂量计要求的能力的更明确的原则证明数据。因此，可携带性研究将确定其他实验室采用危害分析的能力，以及该分析与流动流式细胞仪的兼容性。将通过将自动化样品处理技术和高通量样品分析仪器应用于目前的方法来审查对提高生产能力的需求。其目的是生产一种具有高信息含量的多参数分析，这将显著提高我们目前确定人类暴露于临床相关辐射剂量的能力。未来的研究将调查用于现场使用的高度便携的专用仪器的生产，更广泛地检查更高物种对辐射的反应以及潜在的混杂因素，如非均匀暴露、复合伤害或先前存在的药物影响。通过制定方法，提高我们在辐射事故后确定人类暴露程度和数量的能力，我们可以更有效地管理这些危机局势。 公共卫生相关性：在发生大规模人类辐射暴露事件后，能够快速估计个人辐射暴露的方法将帮助临床医生更好地决定将资源分配给需要资源的人。这项提议旨在扩大评估范围，这是一种新的方法，可以通过监测辐射对循环血细胞的影响来估计接触情况。这些技术最终将增强我国管理这些危险情景的能力。

DESCRIPTION (provided by applicant): Human exposure to radiation, whether by accidental or intentional use, has the potential to impact large populations and severely tax the facilities and resources mandated to respond to such incidents. The current state of clinical management of radiation exposure is lacking in its ability to rapidly and reliably provide relevant human dose estimation. Such information is critical for clinicians to make informed decisions regarding the treatment of patients potentially exposed to hazardous levels of radiation. Thus numerous agencies have placed a high priority on the development of novel radiation biodosimetry methods for use in triage situations. This proposal describes the further evaluation of a novel HemAtotoxicity Response Matrix (HARM) that will provide a multiparametric assessment of radiation-induced damage to the hematopoietic system that can be used to estimate dose. The assay is based on the interrogation of whole blood cell populations for alterations in the number of cells present and the health status of these cells. This is accomplished by using a flow cytometer to count cells and measure alterations in mitochondrial membrane potential (MMP) as an indicator of apoptosis. Preliminary experiments demonstrate that the HARM assay is rapid, minimally invasive, inexpensive and has the potential to discriminate clinically relevant radiation doses. The experiments described in this proposal will provide more definitive proof-of-principle data regarding the ability of the assay to meet the requirements of a functional human radiation biodosimeter. Thus, portability studies will determine the ability of the HARM assay to be adopted by other laboratories and the assay's compatibility with mobile flow cytometry instrumentation. The requirement for increased throughput capabilities will be examined via application of automated sample processing technologies and high throughput sample analysis instrumentation to the current method. The intention is to produce a multiparametric assay with high information content that will significantly improve our current ability to determine human exposure to clinically relevant radiation doses. Future studies will investigate the production of highly portable, dedicated instrumentation for field use, a more extensive examination of higher-species responses to irradiation and potential confounding factors such as non-homogenous exposure, combined injury or pre-existing drug effects. By producing methodologies that will improve our ability to characterize the extent and amount of human exposure following a radiological incident, we can more efficiently manage these crisis situations. PUBLIC HEALTH RELEVANCE: In the aftermath of a large-scale human radiation exposure incident, methods that can rapidly estimate an individual's radiation exposure will help clinicians make better decisions regarding allocation of resources to those that require it. This proposal seeks to extend the assessment a novel methodology that can estimate exposure by monitoring the effects of radiation on circulating blood cells. Such technologies will ultimately enhance our nation's ability to manage these hazardous scenarios.