Project 1: Deployable Software for the Rapid Assessment of Organ Dose Following Radionuclide Intakes

项目1：摘要 该项目将开发可现场部署的软件，该软件与外部探测器测量一起，将 允许对受放射性核素内部污染的个人的器官剂量进行分类报告， 放射性弥散装置（RDD）、简易核装置（IND）或核反应堆事故（NRA） release.这些剂量估计将有助于推动医疗对策的决策，并支持其他形式的预防措施。 暴露评估，如损伤生物标志物。虽然现有的放射分类软件基于单个 一对第50百分位数的成年人和一个有限的RDD放射性核素阵列，我们的软件将允许分类筛选 在不同身高和体重的成年人的现实人群中，将该数据扩展到包括尺寸- 可变的儿童和孕妇，并扩大放射性核素的考虑，包括时间- 依赖裂变产物混合物。我们的第一个假设是一系列经过修改的人体解剖幻象 利用器官内脉管系统的详细模型，将允许准确地说明循环血液， 独立的源区（对寿命较短的放射性核素很重要），并将允许对剂量进行现实的估计 器官实质（对短程辐射很重要）。虽然这些器官的宏观估计 软组织剂量足以进行现场放射分类，本项目将额外进行细化组织 器官毒性剂量反应模型所需的剂量测定。我们的第二个假设是放射性核素 活动在中尺度（组织）和微尺度（细胞）水平上分布不均匀，因此简称为- 在α和β辐射范围内，存在对包括干细胞在内的细胞群的剂量分布， 功能亚单位和免疫细胞。我们将讨论这些假设与以下目标。目标1： 在形态学上多样化的计算人类库中对器官级脉管系统进行建模， 成人、儿童和孕妇。目的2：计算放射性核素S值并评估探测器响应 在整个Aim 1体模库中查找目标3：使用目标2的检测器响应和生物动力学数据 从项目2开始，设计和建造GECAT（伽马射线污染评估工具）。目标4： 扩大GECAT，以包括设计和验证的全身扫描仪所需的放射分类数据 在项目2中。目标5：开发中尺度（组织）和微观尺度（细胞）水平的基于网格的组织学模型 肺，肝，脾和骨髓，当结合X射线荧光显微镜数据时， 项目3（使用来自放射性核素吸入和组织沉积的犬研究的存档组织）将允许 我们计算剂量分布的细胞群体，驱动放射性核素诱导的器官毒性。这 在小鼠放射性核素吸入研究中， 以及暴露后施用新一代放射性核素去放射性剂。

PROJECT 1: ABSTRACT This project will develop field-deployable software which, together with external detector measurements, will permit triage-level reporting of organ dose to individuals internally contaminated with radionuclides following Radiological Dispersion Device (RDD), Improvised Nuclear Device (IND), or Nuclear Reactor Accident (NRA) release. These dose estimates will help drive decisions on medical countermeasures and support other forms of exposure assessment such as injury biomarkers. While existing radiological triage software are based on a single pair of 50th percentile adults and a limited array of RDD radionuclides, our software will permit triage screening across a realistic population of adults of varying heights and weights, expansion of this data to include size- variable children and pregnant females, and expansion of the radionuclides considered to include time- dependent fission product mixtures. Our first hypothesis is that a revised series of human anatomic phantoms with detailed models of intra-organ vasculature will permit accurate accounting for circulating blood as an independent source region (important for shorter-lived radionuclides) and will permit realistic estimates of dose to organ parenchyma (important for short-ranged radiations). While these macroscale estimates of organ parenchyma dose are sufficient for in-field radiological triage, this project will additionally perform refined tissue dosimetry as needed for dose-response modeling of organ toxicity. Our second hypothesis is that radionuclide activity is unevenly distributed at the mesoscale (tissue) and microscale (cellular) levels, and thus for short- ranged alpha and beta radiations, there exists a distribution of dose to cell populations to include stem cells, functional subunits, and immunological cells. We will address these hypotheses with the following aims. Aim 1: Model organ-level vasculature within a morphometrically diverse library of computational humans to include adults, children, and pregnant females. Aim 2: Compute radionuclide S values and evaluate detector responses across the entire Aim 1 phantom library. Aim 3: Use the detector responses from Aim 2 and the biokinetic data from Project 2 to design and construct GECAT (the Gamma-Emitter Contamination Assessment Tool). Aim 4: Expand GECAT to include needed radiological triage data for a whole-body scanner designed and validated within Project 2. Aim 5: Develop mesoscale (tissue) and microscale (cell) level mesh-based histology models of the lungs, liver, spleen, and bone marrow, which when coupled to x-ray fluorescent microscopy data from Project 3 (using archived tissues from canine studies of radionuclide inhalation and tissue deposition), will allow us to compute dose distributions to cellular populations that drive radionuclide-induced organ toxicities. This work will be further expanded using XFM data in murine studies of radionuclide inhalation with both pre-exposure and post-exposure administration of a new generation of radionuclide decorporation agents.