Novel Quantitative Emphysema Subtypes in MESA and SPIROMICS

MESA 和 SPIROMICS 中新的定量肺气肿亚型

• 批准号: 8759952
• 负责人: R Graham BARR
• 金额: $ 45.59万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8759952
• 关键词: Accounting; Alveolus; Atherosclerosis; Autopsy; Cardiac; Cause of Death; Cessation of life; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Code; Cohort Studies; Computer software; Correlation Studies; Development; Diagnosis; Disease; Disease Progression; Environment; General Population; Genetic; Genome; Genotype; Goals; Gold; Hospitalization; Image; Image Analysis; Label; Lead; Learning; Lung; Measures; Methods; Microscope; Modeling; Monitor; Normalcy; Obstruction; Onset of illness; Outcome; Participant; Pathology; Patients; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Population; Prevention strategy; Process; Protocols documentation; Pulmonary Emphysema; Reading; Recruitment Activity; Research; Risk Factors; Sampling; Scanning; Series; Single Nucleotide Polymorphism; Smoker; Structure; Structure of parenchyma of lung; Symptoms; Techniques; Testing; Texture; Time; Tissues; United States; Validation; Variant; Walking; X-Ray Computed Tomography; attenuation; base; clinical practice; clinically relevant; clinically significant; cohort; computerized tools; cost; design; exome; follow-up; functional status; genome-wide; image processing; in vivo; lung imaging; mortality; never smoker; non-smoking; novel; outcome forecast; patient population; prevent; prognostic; prospective; public health relevance; radiologist; rare variant; respiratory; sample fixation; tool; volunteer

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) and emphysema together are the third leading cause of death in the United States. COPD and emphysema are recognized to be heterogeneous diseases, but its underlying mechanisms are not fully understood and there is a lack of precise, biologically based and clinically applicable definitions of emphysema and COPD. In particular, certain subtypes of emphysema have been found to correlate with different risk factors and are therefore likely to represent different diseases. Computed tomography (CT) imaging provides rich in vivo information on the lung parenchyma, airways and vasculature but use of this information is limited. Current approaches for CT-based emphysema quantification and subtyping rely on either crude methods that discard most of the spatial information in CT scans (e.g. thresholding) or on approaches based on supervised learning that simply replicate radiologists' interpretation or use physiological measures as labels. This project will develop the missing computational tools and perform the clinical correlation studies required to exploit CT lung imaging as a new 'microscope' for lung structure examination and will define quantitative emphysema subtypes (QES) for clinical and research use. To reach this goal, we will: (1) develop novel and robust image processing tools for the extraction of emphysema radiological features on thousands of CT scans, (2) perform unsupervised clustering of emphysema radiological features on the large MESA cohort of patients to discover QES and, (3) quantify the levels of normality for QES among homogeneous populations of non-smoking "normal" participants without respiratory symptoms and disease. We will then, starting at the latest in Year 3, demonstrate the clinical relevance of the QES by correlating with symptoms, functional status, respiratory outcomes (hospitalization and death) and examine associations with genotype (genome-wide single nucleotide polymorphisms and exomic rare variants). The power of the analysis is provided by the exploitation of three (MESA, SPIROMICS, EMCAP) very large cohorts of Lung studies - containing CT lung images, respiratory and genetic measures - from normal volunteers and COPD patients. Longitudinal progression of QES in the general population over 10 years (MESA study) and over 5 years among smokers (EMCAP study) will confirm the sensitivity of patients' follow up with CT scans. At the end, QES will be validated to be used to phenotype emphysema into subtypes that have major prognostic significance, contribute to symptoms and have a genetic underpinning. The proposed QES, being derived from automated processing tools, are therefore efficient, low-cost, reproducible, comprehensive, and highly translatable into clinical practice.

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）和肺气肿是美国第三大死亡原因。 COPD和肺气肿被认为是异质性疾病，但其潜在机制尚未完全了解，并且缺乏精确的，基于生物学的和临床适用于肺气肿和COPD的定义。特别是，已经发现某些肺气肿的亚型与不同的危险因素相关，因此可能代表不同的疾病。计算机断层扫描（CT）成像为肺实质，气道和脉管系统提供丰富的体内信息，但使用此信息是有限的。当前的基于CT的肺气肿量化和亚型的方法取决于将CT扫描中大多数空间信息（例如阈值）或基于有监督的学习的方法丢弃的原油方法，这些方法简单地复制了放射科医生的解释或将生理测量方法作为标签。该项目将开发缺失的计算工具，并执行将CT肺成像作为肺结构检查的新“显微镜”所需的临床相关研究，并将定义用于临床和研究使用的定量肺气肿亚型（QES）。为了实现这一目标，我们将：（1）开发出新颖且可靠的图像处理工具，以提取数千次CT扫描的肺气肿放射学特征，（2）（2）在大的ersa ersa同学上对孔隙体放射学特征进行无监督的聚类，以发现QES和QES中的正常性水平，（3）（3）（3）（3）（3）（3）（3）（3）（3）（3） 疾病。然后，我们将从最新的第三年开始，通过与症状，功能状态，呼吸系统结局（住院和死亡）相关，并检查与基因组（全基因组单核苷酸多态性和外生稀有变体）的关联，从而证明了QE的临床相关性。分析的能力是通过对正常志愿者和COPD患者的三种肺部研究（含有CT肺部图像，呼吸和遗传测量的肺部研究）的三种（MESA，螺旋形，EMCAP）的剥削提供的。在10年内，普通人群中QE的纵向进程（MESA研究）和吸烟者中的5年以上（EMCAP研究）将确认患者对CT扫描的敏感性。最后，QE将被验证以表型渗透性为具有重大预后意义的亚型，有助于症状并具有遗传基础。因此，提出的QE是从自动加工工具中得出的，因此是有效的，低成本的，可重现的，全面的，并且可以高度翻译成临床实践。