Ancillary 129Xe Studies for COPDGene

描述（由申请人提供）： COPD是第四大死亡原因，在美国每年花费370亿美元。现有的诊断方法虽然有价值，但不能区分特定的肺病理生理学成分，从而损害了知情治疗和对疾病进展的敏感观察。我们最近开发了利用超极化129氙的MRI方法，可以无创测量三个重要的肺功能参数。它们是（a）每单位体积的肺泡表面积，其损失是肺气肿的直接量度;（B）间隔厚度，其增加反映间质性疾病;和（c）通过气体交换区域的血液通过时间，在存在肺血管疾病时改变。能够获得这些措施的肺功能与非侵入性的方法，不使用电离辐射是新颖的和前所未有的。我们建议证明这些方法用于COPD受试者的表征的实用性。这项研究的成本将大大降低，因为它是一项已经资助的NIH研究的辅助研究，名为COPDGene，正在调查COPD的因果遗传因素。COPDGene正在获得10,500名具有一系列肺功能的吸烟者的肺功能测定、CT和症状问卷数据。我们将研究来自该队列的130名受试者。我们的目标是创建一个功能正常的吸烟者的超极化129 Ω测量量的数据库，然后测量GOLD 1-3期疾病受试者与该标准数据库的偏差。我们将使用全肺数据和成像方法来实现这一点，该方法将允许测量每个受试者内区域性的疾病异质性。我们的目标是证明129 kD肺功能指标与肺生理窘迫症状指标的相关性比现有的肺功能指标更高。公共卫生相关性：我们建议研究测试一种新的非侵入性技术，以确定它是否可以更清楚地识别肺部疾病的具体原因，特别是慢性阻塞性肺疾病（COPD）。这项新技术使用了一种新型的MRI造影剂，称为超极化氙-129气体。拟议的研究将确定新测试的正常值范围，然后测量患有肺部疾病的受试者与该正常值范围的偏差，并将新测试对疾病的预测价值与肺部医生使用的当前测试进行比较。

DESCRIPTION (provided by applicant): COPD is the 4th leading cause of death, costing $37 billion/year in the US. Existing diagnostic methods, while valuable, do not distinguish among specific pulmonary pathophysiological components, thereby compromising informed treatment and sensitive observation of disease progression. We recently developed MRI methods utilizing hyperpolarized 129-Xenon that allow noninvasive measurement of three important pulmonary function parameters. These are (a) alveolar surface area per unit volume, loss of which is a direct measure of emphysema; (b) septal thickness, increases in which reflect interstitial disease; and (c) blood transit time through the gas exchange region, altered in the presence pulmonary vascular disease. The ability to obtain these measures of pulmonary function with a noninvasive method that does not use ionizing radiation is novel and unprecedented. We propose to demonstrate the utility of these methods for the characterization of COPD subjects. The cost of this study will be substantially reduced as it is an ancillary study of an already funded NIH study, named COPDGene that is investigating causal genetic factors for COPD. COPDGene is obtaining spirometry, CT and symptomatic questionnaire data on 10,500 smokers with a range of lung function. We will study 130 subjects from this cohort. Our aims will be to create a database of the hyperpolarized 129Xe measured quantities from smokers with normal function and then to measure deviations from this normative database for subjects with GOLD Stage 1-3 disease. We will do this both with whole lung data and with an imaging approach that will allow measurement of disease heterogeneity regionally within each subject. Our goal is to demonstrate that 129Xe measures of pulmonary function are more highly correlated with symptomatic measures of pulmonary physical distress than existing measures of pulmonary function. PUBLIC HEALTH RELEVANCE: We propose studies to test a new, noninvasive technique to determine whether or not it can more clearly identify the specific causes of lung disease, specifically Chronic Obstructive Pulmonary Disease (COPD). The new technique uses a novel MRI contrast agent, known as hyperpolarized xenon-129 gas. The proposed research will determine what is a normal range of values with the new test, then measure the deviation from this normal range of values in subjects with lung disease, and compare the new test's predictive value for disease with current tests used by lung doctors.