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（由申请人提供）：慢性阻塞性肺疾病（COPD）的全球死亡率持续上升。不幸的是，用于评估其进展的主要技术表现出重要的缺点。肺功能测定法是临床试验中最常用的替代指标，仅提供功能改变的总体指征，在敏感和特异性评估与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）可以生成关键区域异常的出色高分辨率图像，但这些图像大多是解剖图像，仅与生理间接相关，并且患者暴露于电离辐射可能会禁止其在纵向研究中使用。为了解决这些缺点，本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，用于测量人类受试者COPD病理生理学的几个重要方面。所提出的方法将允许同时获得三个区域参数，这些参数一起提供关于肺生理学和微观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）。在多次呼吸的单个采集周期中提取所有这三个度量的能力赋予了几个优点。最重要的是，多呼吸序列的使用导致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COPDGene研究的Temple队列招募的120名COPD患者的肺功能和结构。该队列已经通过CT和肺量测定法得到了很好的表征。我们对这些主题的研究将首先集中在将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参数与CT参数在预测全肺功能变化、加重频率和肺气肿重塑方面的能力。这项研究的广泛影响将是开发一种技术，可以同时获得阻塞性肺疾病的多种非侵入性标志物。这些指标将提供关于COPD的发展和进展的重要生理数据，这将对正在进行的改善这种多变疾病的表型的努力做出有价值的贡献。这些参数还将为新型COPD治疗的纵向研究提供安全和敏感的标志物。