Imaging-based characterization of the COPDGene cohort

COPDGene 队列的基于成像的表征

• 批准号: 9127347
• 负责人: RAHIM R RIZI
• 金额: $ 71.06万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127347
• 关键词: Address; Alveolar; Anatomy; Caring; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Communities; Data; Deterioration; Development; Devices; Diagnosis; Diffusion; Disease; Environmental air flow; Exhibits; Frequencies; Functional disorder; Gases; Gold; Health; Heterogeneity; Hybrids; Image; Imaging Techniques; Ionizing radiation; Longitudinal Studies; Lung; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Methods; Modeling; Monitor; Obstructive Lung Diseases; Outcome; Oxygen; Partial Pressure; Participant; Patient risk; Patients; Phenotype; Physiologic pulse; Physiological; Physiology; Predisposition; Protocols documentation; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Recording of previous events; Recruitment Activity; Reproducibility; Research; Resolution; Respiratory physiology; Scanning; Site; Smoker; Spirometry; Structure; Surrogate Markers; Symptoms; Syndrome; Techniques; Testing; Tidal Volume; Time; Universities; X-Ray Computed Tomography; base; clinically relevant; cohort; cost; disease heterogeneity; follow-up; functional decline; human subject; imaging agent; imaging modality; improved; lung volume; mortality; novel; pulmonary function; respiratory; treatment response

 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.

 描述（由适用提供）：慢性阻塞性肺疾病（COPD）的全球死亡率继续增加。不幸的是，评估其进展的主要技术暴露了重要的缺点。肺活量测定法是临床试验中最常用的替代标记物，仅提供了全球功能改变的指示，并且在敏感和专门评估与COPD相关的异质异常方面遇到了很难。虽然计算机断层扫描（CT）产生了关键区域异常的出色高分辨率图像，但这些图像中的大多数都是解剖学的，仅与生理学间接相关，并且患者暴露于电离辐射中可以指代其在纵向研究中的使用。为了解决这些缺点，该项目旨在完善和测试超极化气体磁共振成像（HP气体MRI）方法，以测量人类受试者COPD病理生理学的几个重要方面。所提出的方法将允许简单地获得三个区域参数，这些参数共同提供了有关肺部生理学和微观结构的细微差异数据：特定通气（SV），氧气的肺泡部分压（PAO2）和明显的扩散系数（ADC）。在多种呼吸中，在单个采集期间提取所有这三个指标的能力赋予了几个优势。最重要的是，使用多呼吸序列会导致更有意义的测量。简单的技术还导致继承所有三个参数的共同注册。一旦优化了多呼吸HP MRI方法，我们将使用它来研究从COPDGENE研究的寺庙队列中招募的120名COPD患者中的肺功能和结构。该队列已经以CT和肺活量测定法进行了很好的特征。我们对这些主题的研究将首先关注将HP MRI指标与这些更既定的技术相关联。然后，我们将根据HP MRI参数在两年的随访期内预测全肺功能变化，加剧频率和杂质重塑的能力，将HP MRI参数与CT参数进行比较。这项研究的广泛影响将是一项技术的开发，该技术可以轻松得出多种阻塞性肺部疾病的非侵入性标记。这些指标将提供有关COPD的发展和发展的重要生理数据，这将为持续的努力做出更好的贡献，以更好地表现这种蛋白质疾病。这些参数还将为新型COPD疗法的纵向研究提供安全和敏感的标记。