Ancillary 129Xe Studies for COPDGene

描述(由申请人提供)： 慢性阻塞性肺病是第四大死因，在美国每年造成370亿美元的损失。现有的诊断方法虽然有价值，但不区分特定的肺部病理生理成分，因此影响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-氙气的MRI方法，允许无创测量三个重要的肺功能参数。它们是(A)单位体积的肺泡表面积，其损失是肺气肿的直接测量；(B)肺间隔厚度的增加，反映间质疾病；以及(C)血液通过气体交换区的时间，在存在肺血管疾病时改变。通过一种不使用电离辐射的非侵入性方法获得这些肺功能测量的能力是新颖和前所未有的。我们建议证明这些方法的有效性，用于描述COPD受试者的特征。这项研究的成本将大大降低，因为它是一项已经得到资助的NIH研究的辅助研究，该研究名为COPDgene，正在调查COPD的因果遗传因素。COPD基因公司正在获得10500名吸烟者的肺活量、CT和症状问卷数据，这些吸烟者的肺功能不同。我们将从这个队列中研究130名受试者。我们的目标将是创建一个来自功能正常的吸烟者的超极化129Xe测量量的数据库，然后测量与这个标准数据库的偏差，用于1-3期疾病。我们将使用全肺数据和一种成像方法来实现这一点，这种方法将允许在每个受试者中测量疾病的区域性异质性。我们的目标是证明与现有的肺功能测量相比，肺功能的129Xe测量与肺生理窘迫的症状性测量更具相关性。公共卫生相关性：我们建议进行研究，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，特别是慢性阻塞性肺疾病(COPD)的特定原因。这项新技术使用了一种新的磁共振造影剂，称为超极化氙气-129气体。这项拟议的研究将确定新测试的正常值范围，然后测量肺部疾病受试者与这一正常值范围的偏差，并将新测试对疾病的预测价值与肺科医生目前使用的测试进行比较。

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.