Rapid Radiation Dose Estimation

描述（由申请方提供）：无论是意外使用还是有意使用，人类暴露于辐射都有可能影响大量人口，并对负责应对此类事件的设施和资源造成严重负担。辐射照射的临床管理的当前状态缺乏快速和可靠地提供相关人体剂量估计的能力。这些信息对于临床医生做出关于治疗可能暴露于危险辐射水平的患者的知情决定至关重要。因此，许多机构都高度重视开发新的辐射生物剂量测定方法，用于分诊情况。该提案描述了对新型血液毒性反应矩阵（HARM）的进一步评价，该矩阵将提供可用于估计剂量的辐射诱导造血系统损伤的多参数评估。该测定基于对全血细胞群的询问，以了解存在的细胞数量和这些细胞的健康状态的变化。这是通过使用流式细胞仪计数细胞和测量线粒体膜电位（MMP）的变化作为细胞凋亡的指标来实现的。初步实验表明，HARM测定是快速的，微创的，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测定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理验证数据。因此，便携性研究将确定HARM检测试剂盒被其他实验室采用的能力以及该检测试剂盒与移动的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当前方法来检查增加通量能力的要求。其目的是产生一个多参数分析与高信息含量，将显着提高我们目前的能力，以确定人体暴露于临床相关的辐射剂量。未来的研究将调查生产的高度便携式，专用仪器，现场使用，更广泛的检查较高的物种对辐射和潜在的混杂因素，如非均匀暴露，联合损伤或预先存在的药物作用的反应。通过制定方法，提高我们在放射性事件后确定人类照射程度和数量的能力，我们可以更有效地管理这些危机局势。 公共卫生相关性：在一个大规模的人体辐射暴露事件发生后，方法，可以快速估计个人的辐射暴露将有助于临床医生作出更好的决定，资源分配给那些需要it.This建议旨在扩大评估一种新的方法，可以估计暴露通过监测辐射对循环血细胞的影响。这些技术将最终提高我们国家管理这些危险情况的能力。

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.