Imaging-based characterization of the COPDGene cohort

 描述(申请人提供)：全球慢性阻塞性肺疾病(COPD)死亡率持续上升。不幸的是，用于评估其进展的主要技术显示出重要的缺陷。肺活量测定法是临床试验中最常用的替代标记物，它只能提供功能改变的全球性指标，而且在敏感和具体评估与COPD相关的异质性异常方面遇到了很大的困难。虽然计算机断层扫描(CT)产生了关键区域异常的高分辨率图像，但这些图像大多是解剖学的，仅与生理学间接相关，患者暴露在电离辐射下可能会阻碍其在纵向研究中的使用。为了解决这些缺陷，该项目旨在改进和测试一种超极化气体磁共振成像(HP GAS MRI)方法，用于测量人体COPD病理生理学的几个重要方面。所提出的方法将允许同时获得三个区域参数，这些参数共同提供了关于肺生理和微结构的细微差别的数据：比通气量(SV)、肺泡氧分压(PAO2)和表观扩散系数(ADC)。在一个采集期内通过多次呼吸提取所有这三个指标的能力提供了几个优势。最重要的是，多呼吸序列的使用带来了更有生理意义的测量。同时技术还导致所有三个参数的固有共同配准。一旦多呼吸HP MRI方法得到优化，我们将使用它来研究从COPD基因研究的Temple队列中招募的120名COPD患者的肺功能和结构。这个队列已经通过CT和肺活量测定得到了很好的特征。我们对这些主题的研究将首先集中于将HP MRI指标与这些更成熟的技术相关联。然后，我们将比较HP MRI参数和CT参数在两年随访期内预测全肺功能变化、恶化频率和肺气肿重塑的能力。这项研究的广泛影响将是开发一种可以同时得出多个阻塞性肺疾病非侵入性标志物的技术。这些指标将提供有关COPD发展和进展的重要生理学数据，这将对正在进行的努力更好地表现这种多变的疾病做出有价值的贡献。这些参数还将为COPD新疗法的纵向研究提供安全和敏感的标记物。

 DESCRIPTION (provided by applicant): The global mortality of chronic obstructive pulmonary disease (COPD) continues to rise. Unfortunately, the predominant techniques for assessing its progression exhibit important shortcomings. Spirometry, the most commonly used surrogate marker in clinical trials, offers only global indications of functional alteration, and it has encountered substantial difficulty in sensitively and specifically assessing the heterogeneous abnormalities associated with COPD. While computed tomography (CT) produces excellent high-resolution images of key regional abnormalities, most of these images are anatomic and only indirectly related to physiology, and the exposure of patients to ionizing radiation can proscribe its use in longitudinal studies. To address these drawbacks, this project aims to refine and test a hyperpolarized gas magnetic resonance imaging (HP gas MRI) approach for the measurement of several important aspects of COPD pathophysiology in human subjects. The proposed method will allow for the simultaneous obtainment of three regional parameters that together offer a nuanced body of data on pulmonary physiology and microstructure: specific ventilation (SV), alveolar partial pressure of oxygen (pAO2), and apparent diffusion coefficient (ADC). The ability to extract all three of these metrics in a single acquisition period over multipe breaths confers several advantages. Most importantly, the use of a multi-breath sequence leads to more physiologically meaningful measurements. The simultaneous technique also results in inherent co-registration of all three parameters. Once the multi-breath HP MRI approach has been optimized, we will use it to study pulmonary function and structure in 120 COPD patients recruited from the Temple cohort of the COPDGene study. This cohort has already been well characterized by CT and spirometry. Our research on these subjects will first focus on correlating HP MRI metrics with these more established techniques. We will then compare HP MRI parameters with CT parameters in terms of their ability to predict whole-lung functional change, exacerbation frequency, and emphysematous remodeling over a two-year follow-up period. The broad impact of this research will be the development of a technique that can simultaneously derive multiple non-invasive markers of obstructive lung disease. These metrics will supply important physiologic data on the development and progression of COPD that will make a valuable contribution to the ongoing effort to better phenotype this protean disease. The parameters will also provide safe and sensitive markers for longitudinal studies of novel COPD therapies.