Anatomically derived airway models to facilitate computational toxicology in mice

 描述(由申请人提供)：小鼠是毒理学风险评估和烟草烟雾暴露最常用的动物模型。由于不可能研究每一种物质的暴露或不同的暴露条件，因此采用数学模型和计算机模拟来研究缺口或扩大实验数据的范围。然而，计算毒理学在小鼠吸入暴露研究中的应用受到限制，因为缺乏建模和特定地点颗粒沉积数据所需的高分辨率准确的气道几何图形。通过将华盛顿大学成像冷冻微型机的独特成像能力与爱荷华大学在高度自动化的呼吸道分割算法方面的专业知识相结合，我们将开发这些方法，并提供四个最常研究的小鼠品系的高分辨率3D几何图形，以及同一动物中特定部位的呼吸道颗粒剂量学。这些高分辨率的数据集将通过一个开放获取的储存库共享，并被其他调查人员用来加快对与呼吸系统有关的健康和疾病的调查。这反过来将提高我们对特定地点的气流以及它们如何影响与职业暴露、空气污染和烟草烟雾有关的健康和疾病中的药物、环境或生物气溶胶沉积的理解。

 DESCRIPTION (provided by applicant): The mouse is the most commonly used animal model for toxicology risk assessments and tobacco smoke exposure. Because it is not possible to study every substance exposure or varying exposure conditions, mathematical models and computer simulations are employed to the gap or to extend the range of experimental data. However, computational toxicology is limited in its application to mouse inhalation exposure studies because of the lack of high-resolution accurate airway geometries needed for modeling and site-specific particle deposition data. By combining the unique imaging capabilities of the Imaging Cryomicrotome at the University of Washington with the expertise in highly-automated airway segmentation algorithms from the University of Iowa, we will develop the methods and provide high-resolution 3D geometries of the four most commonly studied mice strains along with site-specific airway particle dosimetry in the same animals. The high-resolution datasets will be shared through an open access repository and used by other investigators to accelerate investigation of health and diseases related to the respiratory system. This will in turn improve our understanding of site-specific airflows and how they affect drug, environmental, or biological aerosol deposition in health and diseases related to occupational exposures, air pollution and tobacco smoke.