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

项目 1：用于快速评估放射性核素摄入后器官剂量的可部署软件

• 批准号: 10589871
• 负责人: WESLEY E BOLCH
• 金额: $ 39.27万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-10 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589871
• 关键词: 3-Dimensional; Accounting; Adult; Alpha Particles; Anatomic Models; Anatomy; Assessment tool; Back; Beta Particle; Biological Markers; Blood; Blood Vessels; Body Regions; Bone Marrow; Canis familiaris; Cells; Chemicals; Child; Code; Collaborations; Complement; Computer software; Coupled; Data; Deposition; Devices; Diameter; Dose; Elements; Evaluation; Female; Generations; Height; Histology; Human; Immunologics; Individual; Inhalation; Inhalation Exposure; Injury; Intake; International; Libraries; Liver; Location; Lung; Measurement; Measures; Microscopy; Modeling; Mus; Nuclear; Nuclear Reactor Accidents; Organ; Organ Model; Photons; Population; Positioning Attribute; Radiation; Radiation Dose Unit; Radioisotopes; Radiology Specialty; Reporting; Roentgen Rays; Scanning; Series; Slice; Software Tools; Source; Specimen; Spleen; Time; Tissues; Tomogram; Toxic effect; Trees; Triage; Update; Venous; Weight; Work; design; design and construction; detector; dosimetry; image archival system; interest; male; medical countermeasure; microCT; microscopic imaging; pregnant; preservation; response; screening; simulation; skeletal; stem cells; tissue archive

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.

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 允许对体内受到放射性核素污染的个人进行器官剂量分类报告 放射性分散装置 (RDD)、简易核装置 (IND) 或核反应堆事故 (NRA) 发布。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治疗 暴露评估，例如损伤生物标志物。虽然现有的放射分类软件基于单一 一对 50% 的成年人和有限的 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现实成年人口中，扩展该数据以包括尺寸- 可变的儿童和怀孕女性，以及放射性核素的扩展被认为包括时间- 相关裂变产物混合物。我们的第一个假设是一系列经过修改的人体解剖模型 有了详细的器官内脉管系统模型，就可以准确地计算循环血液作为 独立的源区域（对于短寿命放射性核素很重要）并且将允许对剂量进行实际的估计 到器官实质（对于短程辐射很重要）。虽然这些对器官的宏观估计 实质剂量足以进行现场放射学分类，该项目还将额外进行组织细化 根据器官毒性剂量反应模型需要进行剂量测定。我们的第二个假设是放射性核素 活动在中尺度（组织）和微观尺度（细胞）水平上分布不均匀，因此短期内 α和β辐射范围内，存在细胞群（包括干细胞）的剂量分布， 功能亚基和免疫细胞。我们将通过以下目标来解决这些假设。目标 1： 在形态多样的计算人类库中对器官级脉管系统进行建模，包括 成人、儿童和孕妇。目标 2：计算放射性核素 S 值并评估探测器响应 横跨整个 Aim 1 幻像库。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 开始设计和构建 GECAT（伽马发射器污染评估工具）。目标 4： 扩展 GECAT 以包含设计和验证的全身扫描仪所需的放射分类数据 项目 2 中的目标 5：开发中尺度（组织）和微尺度（细胞）级基于网格的组织学模型 肺、肝、脾和骨髓的数据，当与 X 射线荧光显微镜数据结合时 项目 3（使用来自犬类放射性核素吸入和组织沉积研究的存档组织）将允许 我们可以计算驱动放射性核素引起的器官毒性的细胞群的剂量分布。这 工作将进一步扩大，利用 XFM 数据进行预暴露放射性核素吸入的小鼠研究 以及新一代放射性核素脱除剂的暴露后管理。