Detection: Lung Imaging and Profiling

检测：肺部成像和分析

• 批准号: 7231245
• 负责人: Richard A Pierce
• 金额: $ 42.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231245
• 关键词: Affect; Alveolar; Attention; B-Lymphocytes; Breathing; CD8B1 gene; Chronic; Chronic Obstructive Airway Disease; Classification Scheme; Collaborations; Detection; Disease; Elastin; Exposure to; Future; Gases; Genetic; Gold; Heterogeneity; Histology; Image; Imaging technology; Immune; Immunologics; Individual; Infiltration; Inflammatory; Inflammatory Response; Institution; Lead; Lesion; Link; Lung; Lung Transplantation; Lung diseases; Lung volume reduction surgery; Lymphoid; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Methods; Microarray Analysis; Mucous body substance; Nature; Obstruction; Particulate Matter; Pathogenesis; Pathology; Patients; Peripheral; Persons; Principal Investigator; Process; Pulmonary Emphysema; RNA library; Research Infrastructure; Resistance; Resolution; Resources; Sampling; Severities; Severity of illness; Site; Staging; Stimulus; Structure; Structure of parenchyma of lung; Surface; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; Tissues; Transplantation; airway obstruction; alveolar destruction; cell type; disease phenotype; expiration; immunopathology; in vivo; lung imaging; macrophage; novel strategies; programs; regional difference; repaired; size; small airways disease

The defining feature of chronic obstructive pulmonary disease (COPD) is irreversible airflow limitation measured during forced expiration. This results from a varying combination of increased airflow resistance in the small airways and decreased elastic recoil due to emphysematous destruction of lung tissue. We recently showed that significant obstruction of the small airways is present in the lungs of patients with advanced emphysema and that the inflammatory response in the peripheral lung tissue correlates with the severity of COPD as gauged by the GOLD classification scheme. Quantitative analysis of the inflammatory response found strong correlation with the level of lung infiltration by CD8+ T cells, B cells, and macrophages and suggested that these cell types may specially serve to drive the COPD phenotype. Using CT and 3He magnetic resonance imaging (3He MRI) to quantitatively assess regional differences in small airway obstruction and emphysematous destruction in severe COPD, our imaging group has found that regions of mild to moderate disease are found adjacent to sites of severe destruction or obstructive disease even in patients with GOLD 4-stage disease. We hypothesize that the different levels of lesion severity represent different stages in the pathogenesis of the lesions. Our active lung transplantation program, expertise in new imaging technologies and the ability to conduct quantitative analysis of the inflammatory response and tissue remodeling afford a unique opportunity to construct new criteria for assessment of COPD patients. We propose to investigate the pathogenesis of GOLD 4-stage COPD in patients awaiting lung transplant with the following Specific Aims: 1) To test the hypothesis that there is progression in both extent and severity of the inflammatory immune process in regions affected by moderate to severe degrees of emphysema and small airway disease, using morphologic analysis and quantitative immunopathology to characterize the inflammatory immune process. 2) To noninvasively quantify the regional extent and severity of disease separately in subjects with severe COPD using 3He MRI and high-resolution CT imaging. 3) To validate the in-vivo and ex-vivo imaging results in Aim II against the histology in Aim I in order to develop a new approach to quantifying both the extent and severity of emphysema and small airways disease within the lungs of individual patients with COPD.

慢性阻塞性肺疾病（COPD）的定义特征是不可逆的气流限制 在强制呼气期间测量。这是由于空气中增加的气流阻力的不同组合造成的。 小气道和减少弹性回缩由于肺气肿破坏肺组织。我们最近 结果显示，在晚期肺癌患者的肺部存在明显的小气道阻塞， 周围肺组织中的炎症反应与肺气肿的严重程度相关， 根据GOLD分类方案测量的COPD。炎症反应的定量分析 发现与CD8+ T细胞、B细胞和巨噬细胞的肺浸润水平密切相关， 这表明这些细胞类型可能专门用于驱动COPD表型。使用CT和3He 磁共振成像（3He MRI）定量评估小气道的区域差异 阻塞和肺气肿的破坏，我们的成像组发现， 轻度至中度的疾病被发现邻近严重破坏或阻塞性疾病的网站，即使在 GOLD 4期疾病患者。我们假设病变严重程度的不同代表了 病变发病的不同阶段。我们积极的肺移植计划，新领域的专业知识 成像技术和对炎症反应和组织进行定量分析的能力 重塑提供了一个独特的机会，以建立新的标准，COPD患者的评估。我们 建议在等待肺移植的患者中研究GOLD 4期COPD的发病机制， 以下具体目的：1）为了检验以下假设，即在范围和严重程度方面都存在进展， 在受中度至重度肺气肿和小 气道疾病，使用形态学分析和定量免疫病理学来表征 炎症免疫过程。2)非侵入性地量化疾病的区域范围和严重程度 分别在重度COPD受试者中使用3He MRI和高分辨率CT成像。3)验证 体内和离体成像结果与Aim I中的组织学对比，以开发一种新方法 量化肺气肿和小气道疾病的程度和严重程度， 个别COPD患者。