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，与外部探测器测量一起，将 允许对内部受放射性核素污染的个人进行分流级别的器官剂量报告 放射性弥散装置(RDD)、简易核装置(IND)或核反应堆事故(NRA) 放手。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 暴露评估，如伤害生物标志物。虽然现有的放射学分诊软件是基于单个 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流筛查 在不同身高和体重的现实成人人口中，将该数据扩展到包括体型- 可变的儿童和怀孕的女性，以及被认为包括时间的放射性核素的扩大- 依赖的裂变产物混合物。我们的第一个假设是，一系列修改后的人类解剖幻影 器官内血管的详细模型将允许准确地计算循环血液作为 独立源区域(对寿命较短的放射性核素很重要)，并将允许进行实际的剂量估计 器官实质(对短程辐射很重要)。虽然这些对器官的宏观估计 实质剂量足够进行现场放射分流，该项目还将执行精细化组织 器官毒性的剂量-反应模型所需的剂量学。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，因此，简而言之， 在阿尔法和贝塔辐射范围内，存在包括干细胞在内的细胞群体的剂量分布， 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： 在形态不同的计算人类文库中模拟器官水平的血管系统，以包括 成年人、儿童和怀孕的雌性。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幻影库。目标3：使用来自目标2的探测器响应和生物动力学数据 从项目2设计和建造GECAT(伽马发射器污染评估工具)。目标4： 扩展GECAT以包括设计和验证的全身扫描仪所需的放射学分诊数据 在项目2.目标5：开发基于网格的中尺度(组织)和微尺度(细胞)组织学模型 肺、肝、脾和骨髓，当与x射线荧光显微镜数据相结合时， 项目3(使用犬类放射性核素吸入和组织沉积研究的存档组织)将允许 美国计算驱动放射性核素诱导的器官毒性的细胞群体的剂量分布。这 将利用XFM数据进一步扩大在小鼠放射性核素吸入和暴露前研究中的工作 以及新一代放射性核素脱孔剂的暴露后给药。