CAREER: Biomechanics of Tension-Induced Lung Tissue Fracture and Subsequent Pulmonary Air Leak

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。该学院早期职业发展（Career）奖将支持研究机械通气如何损伤软肺组织。这项工作还将研究可能导致肺部空气泄漏的组织损伤。机械通气已成为许多临床并发症的救命疗法。本研究将采用工程方法来更好地了解长时间机械通气后肺组织的生物物理特性。首先，本工作将研究肺组织强度与漏气损伤之间的关系。其次，这项工作将使用声学来量化空气泄漏伤害的严重程度。这项工作很重要，因为肺组织如何对反复的气压负荷作出反应仍然知之甚少。众所周知，在机械通气过程中，由于肺部的反复强力拉伸，肺组织可能会受损和撕裂。通过受损的组织，吸入的空气会渗入胸腔，导致呼吸衰竭。这项工作的结果最终有助于减少机械通气期间的肺损伤。这项工作将通过对肺组织行为的基本见解而造福社会。它还将促进创新技术的发展。此外，这项研究将与教育相结合，为当地少数民族学生提供以学生为中心的STEM体验。该项目的总体研究目标是了解肺部的内在变形力学是如何在反复过度膨胀的情况下动态改变的，以及这种改变是如何与张力引起的肺软组织骨折（可能导致肺部空气泄漏）联系在一起的。因此，本项目将研究肺组织断裂和随后的空气泄漏的量化特征，为张力性肺组织损伤的生物力学提供一套全面的解释。本研究有两个研究目的：1)确定机械通气时肺组织力学特性对肺组织骨折发生、传播和消退的影响；2)识别气流与组织动态相互作用产生的漏气声的声学特征，评价声信号作为漏气损伤量化指标的作用。该研究的成功完成将产生新的知识，可以为软组织的非线性变形和断裂力学提供基本的见解，最终提供改进的诊断、治疗和预防张力性肺损伤。此外，这项工作将使PI在肺力学方面开启一个有影响力和可持续的研究生涯，并成为一名致力于减轻少数民族学生学习障碍的教育家。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).This Faculty Early Career Development (CAREER) award will support research to investigate how soft lung tissue can be injured by mechanical ventilation. This work will also study tissue injury that can lead to air leak in the lungs. Mechanical ventilation has been a life-saving therapy for many clinical complications. This research will use an engineering approach to better understand the biophysical characteristics of lung tissue that undergoes prolonged mechanical ventilation. First, this work will study the relationship between the strength of lung tissue and injuries caused by air leak. Second, this work will use acoustics to quantify the severity of air leak injuries. This work is important because how the lung tissue responds to repeated air pressure loading remains poorly understood. It is known that lung tissue can be damaged and torn due to repeated forceful stretching of the lung during mechanical ventilation. Through the damaged tissue, inhaled air can leak into the chest cavity and cause respiratory failure. The results of this work can ultimately help minimize lung injury during mechanical ventilation. The work will benefit society by generating fundamental insights into how lung tissue behaves. It will also facilitate the development of innovative technologies. Further, this research will be integrated with education to provide student-centered STEM experiences to local minority students. The overall research goal of this project is to understand how the intrinsic deformation mechanics of the lung is altered dynamically in response to repeated overdistension, and how the alternation is linked to tension-induced fracture of soft lung tissue that can lead to pulmonary air leak. Accordingly, this project will investigate quantifiable characteristics of lung tissue fracture and subsequent air leak to provide a set of comprehensive explanations for the biomechanics of tension-induced lung tissue injury. This study is organized under two research objectives: 1) determining the impacts of mechanical properties of lung tissue on initiation, propagation, and resolution of lung tissue fracture during mechanical ventilation; and 2) identifying acoustic characteristics of air leak sound generated via dynamic airflow-tissue interaction to evaluate the role of acoustic signal as a quantifiable indicator of air leak injury. Successful completion of the study will generate new knowledge that can provide fundamental insights into non-linear deformation and fracture mechanics of soft lung tissue, ultimately offering improved diagnosis, treatment, and prevention of tension-induced lung injury. Further, the work will allow the PI to initiate an impactful and sustainable research career in lung mechanics, and become an educator who is dedicated to mitigating learning barriers for underrepresented minority students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.