3D IMAGING & COMPUTER MODEL OF THE RESPIRATORY TRACT

描述(由申请人提供)： 呼吸道是人体与环境的主要接口之一。它的主要结构部件旨在最大限度地进行气体交换并提供感官输入(即气味检测)。因此，呼吸道可能成为导致大量人类疾病的各种空气传播环境因子的靶子。疾病引起的呼吸系统结构或功能的改变可以极大地影响与环境的接口，并改变生活质量。为了提高我们预测正常或潜在敏感人群的空气污染物(气体、蒸气、颗粒物或大气释放的化学/生物武器)或故意吸入药物的后果的能力，一个由数学家、物理学家、化学家和生物学家组成的跨学科团队将开发动物和人类呼吸道的三维(3D)生物模型。这一伙伴关系的总体具体目标是：(1)开发和应用磁共振成像和荧光微球技术，以确定呼吸道的动态、3D结构和功能特性；(2)确定3D细胞的组织和代谢能力；(3)开发和扩展3D建模的软件和计算能力，以及用于细胞-器官模型集成的放大技术；(4)开发具有明确可变性测量的归一化大鼠几何图谱；(5)进行体内气体交换和颗粒剂量学研究，用于模型验证和识别模型不确定性；以及(6)提供一个基于网络的“肺生理组”平台，用于传播和培训研究人员和临床医生使用成像和带注释的模型数据库。设计了五个项目，为开发和验证计算模型提供关于呼吸系统动态结构和功能的必要数据。为支持这五个项目，将在高级成像、计算和数据库/模型访问以及外部用户培训方面设立三个技术开发核心。第四个核心将作为行政接口，并将在参与机构和项目之间提供统计支助。

DESCRIPTION (provided by applicant): The respiratory tract is one of the main interfaces between the body and the environment. Its major structural components are designed to maximize gas exchange and provide sensory input (i.e. odor detection). As such, the respiratory tract can become a target for a broad range of airborne environmental agents contributing to an expansive array of human diseases. Alterations in the structure or function of the respiratory system by diseases can dramatically affect the interface with the environment and alter the quality of life. To improve our ability to predict the dosimetry and thus the consequences of airborne pollutants (gases, vapors, particulates or atmospheric releases of chemical/biological weapons) or drugs intentionally administered by inhalation for normal or potentially sensitive populations, 3-dimensional (3D), biologically based models of the respiratory tracts of animals and humans will be developed by a cross-disciplinary team of mathematicians, physicists, chemists, and biologists. The overall specific aims of this partnership are to: (1) develop and apply magnetic resonance imaging and fluorescent microsphere techniques to determine the dynamic, 3D structural and functional properties of the respiratory tract; (2) determine the 3D cellular organization and metabolic capacity; (3) develop and extend software and computational capabilities for 3D modeling and upscaling techniques for cellular-to-organ model integration; (4) develop a normalized atlas of rat geometries with explicit measures of variability; (5) conduct in vivo gas exchange and particulate dosimetry studies for model validation and identification of model uncertainties; and (6) provide a web-based "pulmonary physiome" platform for dissemination and training of researchers and clinicians in the use of imaging and annotated model databases. Five projects are designed to provide the necessary data on the dynamic structure and function of the respiratory system for the development and validation of the computational models. To support these five projects, three technology development cores will be established in advanced imaging, computation, and database/modeling access and training for external users. A fourth core will serve as an administrative interface and will provide statistical support among the participating institutions and projects.