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: 10327396
• 负责人: WESLEY E BOLCH
• 金额: $ 37.45万
• 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/10327396
• 关键词: 3-Dimensional; Accounting; Address; Adult; Alpha Particles; Anatomic Models; Anatomy; Assessment tool; Back; Beta Particle; Biological Markers; Blood; Blood Vessels; Body Regions; Bone Marrow; Caliber; Canis familiaris; Cells; Centers for Disease Control and Prevention (U.S.); Chemicals; Child; Code; Collaborations; Complement; Computer software; Coupled; Data; Deposition; Devices; Dose; Elements; Evaluation; Female; Generations; Hand; 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; base; child protection; 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 该项目将开发可剥离的软件，并将 允许对内部受放射性核素内部污染的个体进行分类级报告 放射学分散装置（RDD），即兴核装置（IND）或核反应堆事故（NRA） 发布。这些剂量估计将有助于提出有关医疗对策的决定，并支持其他形式的 暴露评估，例如伤害生物标志物。虽然现有的放射分类软件是基于单个的 一对50％的成年人和有限的RDD放射性核素，我们的软件将允许分类筛选 在各种高度和体重不同的成年人中，该数据的扩展包括大小 - 可变的儿童和孕妇，以及被认为包括时间的放射性核素的扩张 依赖裂变产物混合物。我们的第一个假设是经过修订的一系列人类解剖幻像 凭借详细的管道内脉管系统模型将允许准确地核算循环血液作为一种 独立的源区域（对寿命较短的放射性核素很重要），将允许对剂量进行现实估计 到器官实质（对于短距离辐射很重要）。这些器官的宏观估计值 实质剂量足以容纳场地放射学分类，该项目将进一步进行精制组织 根据需要进行剂量反应建模的器官毒性的剂量测定。我们的第二个假设是放射性核素 活性分布在中尺度（组织）和微观（细胞）水平上，因此 远程α和β辐射，存在剂量到细胞群的分布，包括干细胞， 功能亚基和免疫细胞。我们将以以下目的解决这些假设。目标1： 模型器官级的脉管系统在形态学上多样化的计算人类库中，包括 成人，儿童和怀孕的女性。目标2：计算放射性核素的值并评估检测器响应 在整个目标1幻影库中。 AIM 3：使用AIM 2和生物动力学数据的检测器响应 从项目2到设计和构建GECAT（伽玛 - 发射机污染评估工具）。目标4： 将GECAT扩展到包含所需的放射分类数据，用于设计和验证的全身扫描仪 在项目2中。目标5：开发中尺度（组织）和微观（细胞）基于网格的组织学模型 肺，肝脏，脾和骨髓的含量，当与X射线荧光显微镜数据偶联时 项目3（使用放射性核素吸入和组织沉积的犬类研究的存档组织）将允许 我们要计算剂量分布到驱动放射性核素诱导的器官毒性的细胞群体。这 在放射性核素吸入的鼠研究中，将进一步扩展工作 以及新一代放射性核素装饰剂的暴露后给药。