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

描述(由申请人提供)：这项研究的主要目标是探索一种负责肺部有效气体交换的新机制。只有当区域通风和血液流动紧密匹配时，才能进行有效的气体交换。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肺部疾病治疗方法，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显微成像，提供有关肺解剖的高分辨率信息以及区域通风和灌注图，以验证我们的假设，即区域灌流和通风通过共享的呼吸道和血管树的几何形状而紧密匹配。本项目将开发的高度自动化的计算机辅助分割方法将提供从大鼠肺的冰冻切片成像数据中提取和分割复杂的呼吸道和肺动静脉树的能力。这将使我们能够a)比较成对的气道和血管节段的电导率，以确定它们是否相似，以及b)将基于几何树特性预测的终端通气量和血流量与通过冷冻显微图像测量的结果相关联。我们的研究将提供新的见解和对肺复杂和交织的分布系统中如何匹配通风和灌流的机制的理解。从长远来看，我们预计所获得的知识以及开发的新的计算机辅助分析方法将使我们能够更好地了解和治疗肺气肿和肺动脉高压等肺部疾病，这些疾病的呼吸道和血管树变得分离，低效的气体交换造成严重的发病率，并可能危及生命。 与公共健康相关：这个项目将使我们能够利用先进的成像和计算机辅助分析方法，在动物研究的基础上，获得关于肺部有效气体交换的基本机制的新知识。更好地了解肺通气和肺灌注之间的区域匹配是开发慢性阻塞性肺疾病(COPD)等肺部疾病新疗法的基础。

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).