Multiscale Study of the Respiratory Airway Mechanics for Cellular Inflammation

机械通气时呼吸道中的细胞炎症反应是一个复杂的过程，涉及多个长度尺度上的呼吸道压力/应变和细胞组织顺应性。为了了解这一复杂的炎症过程并帮助实验，建立计算模拟是必要的，并可能导致呼吸衰竭患者机械通气的范式转变。这项拟议研究的总体目标是开发一个多尺度的细胞炎症模型，在机械通气过程中顺应肺几何形状。具体的研究目标是：(1)建立基于连续描述的器官水平模型，用于研究呼吸道的行为；(2)建立基于连续描述的组织水平模型，用于研究呼吸道组织的应力/应变行为；(3)建立基于离散系统的细胞水平模型，用于研究细胞炎症行为。这些多层次的计算模拟结果将被用来建立相关性，这些相关性将能够测试各种机械通风策略相对于气道压力和应力参数的结果，以将对肺的损害降至最低。拟议研究的智力优势来自于将组织炎症的离散细胞模型与组织和器官水平的连续描述相结合，以捕捉机械通风引起的肺几何中复杂的压力/应力和细胞炎症参数。除了开发了解机械通风效果的模型外，研究结果还将提供新的呼吸道计算模拟模型(流固相互作用)和细胞水平的基于规则的炎症模型，这可能有助于进一步评估肺应激和细胞炎症参数的最佳特性，同时将对肺组织的损害降至最低。这项拟议研究的广泛影响源于多尺度计算模型的发展，这将促进我们对避免患者肺部相关损伤的机械通气策略的了解。这项拟议的研究将工程模拟技术的进步与临床应用相结合，开创了一种新的机械通风方法。对社会的好处可能包括修复由多种原因导致的呼吸衰竭患者的肺损伤。如果成功，该项目将为患者特定的计算模拟提供场所，以避免儿童和成人发生呼吸衰竭。研究成果将整合到PI的教育活动中，并通过里士满？S？Questers？等项目探索与中学生的外展活动。计划，和VCU的YMCA Metro青少年。将通过期刊和会议出版物以及一个网站进行传播，以进行呼吸衰竭的虚拟模拟和避免呼吸衰竭的策略。

Cellular inflammatory responses in respiratory airways during mechanical ventilation is a complex process dealings airway pressures/strains and cellular tissue compliance at multiple length scales. In order to gain understanding of this complex inflammation process and to aid in experiments, building computational simulations is necessary and may lead to a paradigm shift in mechanical ventilation for patients with respiratory failures. The overall goal of the proposed research is to develop a multi-scale model of cellular inflammation in compliant lung geometry during mechanical ventilation. The specific research objectives are: (i) Development of an organ level model based on continuum description for studying the behaviors of the respiratory airway; (ii) Development of a tissue level model based on continuum description for studying the stress/strain behaviors of the airway tissue; and (iii) Development of a cellular level model based on discrete system for studying the behaviors of the cellular inflammation. Results of these computational simulations at multiple levels will be used to develop correlations that will be capable of testing the outcomes of various mechanical ventilation strategies with respect to airway pressures and stress parameters to minimize the potential for damage to the lung.The intellectual merit of the proposed research come from integrating discrete cellular models of tissue inflammation with continuum description of tissue and organ level models to capture the complex pressures/stresses and cellular inflammation parameters in lung geometry due to mechanical ventilation. Besides developing models to understand the mechanical ventilation effects, the research results will provide new computational simulation models of the airway (fluid-solid interactions) and a rule based inflammation model at a cellular level which might help further to assess optimal characteristics for lung stresses and cellular inflammation parameters while minimizing the potential for damage to the lung tissue. The broad impact of this proposed research stems from the development of multi-scale computational models which will advance our knowledge on mechanical ventilation strategies to avoid lung related injuries in patients. The proposed research pioneers the beginning of a new approach to mechanical ventilation by combining advances in engineering simulation techniques with clinical applications. The benefits to society may include repairing lung injury in patients with respiratory failures resulting from multiple sources. If successful, this project will open a venue for patient specific computational simulations to avoid respiratory failures both in children and adults. The research results will be integrated into PI's educational activities and explore outreach activities with middle school and high school students through programs such as Richmond?s ?QUESTERS? program, and YMCA Metro Teens at VCU. Dissemination will be through journal and conference publications along with a website for carrying out virtual simulations of respiratory failures and strategies to avoid them.