Rapid Radiation Dose Estimation

描述（由申请人提供）：人类暴露于辐射，无论是意外还是故意使用，都有可能影响大量人口，并严重影响用于应对此类事件的设施和资源。目前的辐射照射临床管理缺乏快速、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在治疗可能暴露于危险辐射水平的患者时做出知情决定至关重要。因此，许多机构高度重视发展用于分诊情况的新型辐射生物剂量测定方法。本提案描述了一种新的血液毒性反应矩阵（HARM）的进一步评估，该矩阵将提供辐射诱导的造血系统损伤的多参数评估，可用于估计剂量。该分析是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况的变化。这是通过使用流式细胞仪来计数细胞和测量线粒体膜电位（MMP）作为细胞凋亡指标的变化来完成的。初步实验表明，HARM测定快速、微创、廉价，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更明确的原理证明数据，证明该分析是否能够满足功能性人体辐射生物剂量计的要求。因此，可移植性研究将确定HARM测定法被其他实验室采用的能力，以及该测定法与移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当前方法来检查对提高吞吐能力的需求。目的是建立一种信息含量高的多参数测定方法，这将显著提高我们目前确定人体暴露于临床相关辐射剂量的能力。未来的研究将调查生产高度便携的专用仪器供现场使用，更广泛地检查更高物种对辐射的反应和潜在的混杂因素，如非均匀暴露、复合损伤或预先存在的药物效应。通过制定方法，提高我们描述放射性事件后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情况。

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.