Computer-aided analysis of mechanisms matching ventilation and perfusion in rats

描述（由申请人提供）：本研究的主要目标是探索肺部有效气体交换的新机制。有效的气体交换只能发生在区域通风和血液流动紧密匹配的情况下。我们目前对这些基本机制的了解不足以理解和开发更有效的治疗肺部疾病，如慢性阻塞性肺疾病（COPD）、肺气肿、急性肺损伤或支气管肺发育不良。在这个项目中，我们将利用大鼠肺的冷冻组成像，提供关于肺解剖和区域通气和灌注图的高分辨率信息，来验证我们的假设，即区域灌注和通气通过气道和血管树的共享几何形状紧密匹配。本项目开发的高度自动化计算机辅助分割方法将提供从大鼠肺冷冻组成像数据中提取和分割复杂的气道和肺动脉静脉树的能力。这将允许我们a)比较配对气道和血管段的电导，以确定它们是否相似；b)将基于几何树特性的预测终端通气和血流与通过冷冻组图像测量的结果相关联。我们的研究将为通气和灌注如何在肺的复杂和交织分布系统中匹配提供新的见解和机制理解。从长远来看，我们期望获得的知识，以及开发的新型计算机辅助分析方法，将使我们能够更好地理解和治疗肺气肿和肺动脉高压等肺部疾病，在这些疾病中，气道和血管树被分离，低效的气体交换造成了严重的发病率，并可能危及生命。

DESCRIPTION (provided by applicant): The primary goal of this research is to explore a new mechanism responsible for efficient gas exchange in the lungs. Efficient gas exchange can only occur if regional ventilation and blood flow are closely matched. Our current understanding of these basic mechanisms is inadequate to understand and develop more effective treatments for lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, acute lung in- jury, or bronchopulmonary dysplasia. In this project, we will utilize cryomicrotome imaging of rat lungs, which provides high-resolution information about lung anatomy and maps of regional ventilation and perfusion, to test our hypothesis that regional perfusion and ventilation are tightly matched through the shared geometries of the airway and vascular trees. The highly-automated computer-aided segmentation methods to be developed in this project will provide the ability to extract and segment the complex airway and pulmonary artery and vein trees from cryomicrotome imaging data of rat lungs. This will allow us a) to compare the conductances of paired airway and vascular segments to determine if they are similar and b) correlate the predicted terminal ventilation and blood flows based on geometric tree properties with those measured via the cryomicrotome images. Our investigations will provide new insights and a mechanistic understanding of how ventilation and perfusion are matched within the complex and interwoven distributions systems of the lung. In the long-term we expect that the gained knowledge, as well as the developed novel computer-aided analysis methods, will enable us to better understand and treat lung diseases like emphysema and pulmonary hypertension where the airway and vascular trees become dissociated and inefficient gas exchange creates significant morbidity and can be life-threatening. PUBLIC HEALTH RELEVANCE: This project will allow us to gain new knowledge about the fundamental mechanisms of efficient gas exchange in lungs based on an animal study by utilizing advanced imaging and computer-aided analysis methods. A better understanding of the regional matching between pulmonary ventilation and perfusion is fundamental to developing new treatments for lung diseases like chronic obstructive pulmonary disease (COPD).