ASSESSMENT OF LUNG FUNCTION IN MICE

描述（由申请人提供）：评估小动物，特别是小鼠的肺机械功能，对于肺部疾病病理生理学的许多研究至关重要。强制振荡技术应用于麻醉气管造口动物，提供最准确和具体的肺功能评估，但具有高度侵入性。有意识动物的无约束容积脉搏图提供了一个名为PenH的参数，但这个数量实际上反映的是对呼吸的控制，而不是肺力学。因此，目前还没有完全无创的方法可用于确定小动物的肺功能，尽管在这方面继续错误地使用PenH。然而，我们的研究表明，如果能与肺体积变化的独立测量相结合，无约束容积描记将为跟踪肺力学功能的变化提供一种有效的手段。因此，我们建议的目标是通过将其与一种利用胸腔正交视频图像测量肺体积变化的创新方法相结合，从而扩展无约束的体积脉搏图。到目前为止，我们的研究已经确定了这种方法的可行性，这将成为无约束视频辅助容积脉搏波（UVAP）的基础。我们将在三个具体目标中开发和验证UVAP：具体目标1：通过将用于跟踪肺体积变化的正交视频系统整合到加热和湿化的身体体积脉搏仪中，开发无约束的视频辅助体积脉搏仪（UVAP）。特定目的2：定义小鼠制备和维持如何决定UVAP测定肺功能的准确性。特异性目的3：通过使用UVAP跟踪肺部疾病小鼠模型的气道阻力变化来验证UVAP。这项工作的结果将为研究人员提供一种无创跟踪小鼠气道阻力变化的工具，这对于快速筛选大量动物以及对有价值的肺部疾病小鼠模型进行无损检测是非常宝贵的。

DESCRIPTION (provided by applicant): The assessment of lung mechanical function in small animals, particularly mice, is essential for many investigations into the pathophysiology of pulmonary disease. The forced oscillation technique applied in anesthetized tracheostomized animals provides the most accurate and specific assessment of lung function but is highly invasive. Unrestrained plethysmography in conscious animals provides a parameter called PenH, but this quantity is actually a reflection of the control of breathing and not lung mechanics. Thus, there is currently no completely noninvasive method available for determining lung function in small animals, despite the continued erroneous use of PenH in this regard. However, our research has shown that unrestrained plethysmography would provide a valid means for following changes in lung mechanical function if it could be coupled to independent measurements of changes in lung volume. Accordingly, the goal of our proposal is to extend unrestrained plethysmography by coupling it to an innovative method of measuring changes in lung volume using orthogonal video images of the thorax. Our studies to date have established the feasibility of this approach, which will form the basis of unrestrained video-assisted plethysmography (UVAP). We will develop and validate UVAP in three specific aims: SPECIFIC AIM 1: To develop unrestrained video-assisted plethysmography (UVAP) by incorporating an orthogonal video system for tracking changes in lung volume into a heated and humidified body plethysmograph. SPECIFIC AIM 2: To define how mouse preparation and maintenance determine accuracy of lung function measurement by UVAP. SPECIFIC AIM 3: To validate UVAP by using it to track changes in airway resistance in mouse models of lung disease. The results of this work will provide researchers with a tool for noninvasively following changes in airway resistance in mice, which should prove invaluable for the rapid screening of large numbers of animals, and for the non-destructive testing of valuable mouse models of lung disease.