EVALUATION OF ENDOBRONCHIAL INTERVENTIONS FOR COPD VIA CT AND 3HE MRI

描述（由申请人提供）：我们的总体目标是确定CT和mr成像技术，这些技术将最好地指导和告知世界各地正在开发的两种微创COPD手术治疗方法：从引导气道到肺气肿实质的支气管内支架支持导管，以及在严重肺气肿肺区域实现体积缩小的支气管内单向出口阀。这两种建议的干预措施在减轻严重肺气肿患者的呼吸困难方面都显示出巨大的希望，对于严重肺气肿，除了肺移植和肺减容手术之外，没有其他治疗选择。尽管前景广阔，但目前还没有确定的方法来确定干预的目标区域或预测疗效。本文提出的工作将在晚期COPD移植切除的人类肺中进行，原因有两个：人类肺气肿在任何动物模型中都不能很好地复制，介入放置可以在随机位置，允许在不考虑患者结果的情况下获得一系列功能结果，并允许测试关于区域侧支通气和区域肺功能的潜在假设。虽然这里提出的成像程序都是离体的，但它们可以并且已经在体内使用。通过将干预后的肺功能改善与定量的3He MRI和CT结果（干预前和干预后）相关联，我们将能够证明肺成像技术在以下方面的效用：(1)指导在给定肺内安装瓣膜或支架的内镜操作；(2)预测给定干预后的功能改善结果。该提案旨在通过华盛顿大学和宾夕法尼亚大学/弗吉尼亚大学这两个在胸部成像和严重慢性阻塞性肺病治疗方面处于世界领先地位的机构的联合努力，向有效和可预测的肺气肿内窥镜治疗迈出重要一步。

DESCRIPTION (provided by applicant): Our overall goal is to identify CT and MR-imaging techniques that will best guide and inform the two minimally-invasive surgical therapies for COPD which are under development around the world: endobronchial stent-supported conduits from conducting airways to emphysematous parenchyma, and endobronchial one-way exit valves to effect volume reduction in severely emphysematous lung regions. Both proposed interventions show great promise at reducing dyspnea in patients with severe emphysema, for which there is no therapeutic treatment option other than lung transplantation and, for a few, lung volume reduction surgery. Despite the great promise, there is no currently identified method for identification of target regions for the intervention or for efficacy prediction. The work proposed here will be performed in human lungs removed at transplant for advanced COPD for two reasons: human emphysema is not well replicated in any animal model, and interventional placement can be at random locations, allowing a range of functional results without regard to patient outcomes and allowing testing of the underlying assumptions about regional collateral ventilation and regional lung function. Though the imaging procedures proposed here are all ex vivo, they can be and have been employed in vivo. By correlating lung functional improvements after intervention with quantitative 3He MRI and CT results (pre- and post-intervention), we will be able to demonstrate the utility of pulmonary imaging techniques to (i) guide the endoscopic installation of valves or stents in a given lung and (ii) predict the functional improvement outcomes for a given intervention. This proposal aims to make a significant step forward toward effective and predictable endoscopic treatment of emphysema, through a combined effort at two sites (Washington University and the University of Pennsylvania / University of Virginia) that are world leaders in thoracic imaging and treatment of severe COPD. PUBLIC HEALTH RELEVANCE: Chronic obstructive pulmonary disease (COPD) affects between 11 and 24 million Americans and is a major cause of suffering and premature death. Two minimally- invasive surgical procedures are under development to treat severe COPD and show great promise but results vary significantly among patients. We propose new imaging methods via CT and MRI to test these interventions, to eventually improve patient selection, choice of lung target areas in individuals, and reliable prediction of success of these procedures in individual patients.