In vivo human lung morphometry with hyperpolarized 3He MRI and CT: effects of aging, smoking, and COPD

使用超极化 3He MRI 和 CT 进行体内人肺形态测量：衰老、吸烟和 COPD 的影响

• 批准号: 9340827
• 负责人: DMITRIY A YABLONSKIY
• 金额: $ 70.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9340827
• 关键词: Acceleration; Adult; Affect; Age; Aging; Air; Alveolar; Alveolar Duct; Alveolar sac; Alveolar wall; Alveolus; Blood capillaries; Cause of Death; Cessation of life; Chest; Chronic Obstructive Airway Disease; Collection; Data; Deterioration; Development; Diffusion; Disease; Distal; Environment; Event; Gases; Generations; Genetic; Goals; Gold; Heterogeneity; Human; Imagery; Imaging Techniques; Individual; Laboratories; Lung; Magnetic Resonance Imaging; Measurement; Measures; Medical History; Oxygen; Participant; Pathology; Physiology; Prevalence; Prevention strategy; Process; Public Health; Pulmonary Emphysema; Quality of life; Respiratory physiology; Role; Rupture; Sampling; Severities; Severity of illness; Smoker; Smoking; Spatial Distribution; Specimen; Structure; Structure of parenchyma of lung; Symptoms; Techniques; Testing; Tissues; Trees; Walking; X-Ray Computed Tomography; age effect; age related; aged; base; capillary; cigarette smoking; disease phenotype; experience; in vivo; innovation; lung volume; morphometry; multimodality; never smoker; novel; novel strategies; prevent; public health relevance; pulmonary function; small airways disease; tool; treatment strategy

 DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) has become the third most common cause of death in the U.S., and the number of COPD-associated deaths has doubled over the past 20 years. Age, environmental, and genetic factors affect COPD development and progression. While studies of COPD have evaluated different aspects of lung physiology, pathology, and function very little in vivo information exists on the structure and the role of the acinar airways, even though these airways represent 95% of the lung volume and function as the major gas-exchanging unit. This proposal has an overarching goal of developing a new understanding of the effects of aging, cigarette smoking, and COPD on the lung, by measuring and differentiating all aspects of the structural changes in acinar airways among these conditions. We also aim to understand the interplay between disease of small conducting airways and changes in the structure of acinar airways in regions of gas trapping which are thought to be early events leading to emphysema. Building on our prior discovery of anisotropic 3He gas diffusion in acinar airways, we developed and validated the innovative imaging technique of lung morphometry with hyperpolarized 3He magnetic resonance imaging (MRI) that provides unique in vivo quantitative information on the structure and spatial distribution of acinar airways for this study. We will combine 3He morphometric data with quantitative CT data to obtain unique information on parenchymal (alveolar walls including capillaries) and non-parenchymal (non-capillary vessels, etc.) lung tissue, as well as on disease of small conducting airways. Our Specific Aims focus on establishing quantitative relationships between structural alterations in acinar and small airways and declines in lung function: Aim 1: Identify and compare structural mechanisms of the progressive deterioration in lung function associated with aging in "healthy" never-smokers and "healthy" smokers, and differentiate contributions of acinar and small airway disease, by using quantitative metrics determined by MRI-based in vivo lung morphometry and quantitative CT. Aim 2: Identify the structural mechanisms of the progressive deterioration in lung function associated with smoking-related COPD, and differentiate the mechanisms of age-related structural changes in the acinar and small airways (in "healthy" never-smokers and "healthy" smokers) from those due to COPD, by using quantitative metrics determined by MRI-based in vivo lung morphometry and quantitative CT. We expect to develop a new approach for assessing the effects of aging and COPD on lung structure and function, provide a new understanding of how aging, cigarette smoking, and emphysema cause lung acinar structural changes and associated deterioration in lung function, and propose novel targets for preventing and treating the major public health problem of COPD.

 描述（由申请人提供）：慢性阻塞性肺疾病 (COPD) 已成为美国第三大常见死因，且与 COPD 相关的死亡人数在过去 20 年中翻了一番。年龄、环境和遗传因素影响慢性阻塞性肺病的发生和进展。虽然 COPD 的研究评估了肺生理学、病理学和功能的不同方面，但关于腺泡气道的结构和作用的体内信息却很少，尽管这些气道占肺体积的 95%，并且作为主要的气体交换单位发挥作用。该提案的总体目标是通过测量和区分这些条件下腺泡气道结构变化的各个方面，对衰老、吸烟和慢性阻塞性肺病对肺部的影响有一个新的认识。我们还旨在了解小传导气道疾病与气体滞留区域腺泡气道结构变化之间的相互作用，气体滞留区域被认为是导致肺气肿的早期事件。 基于我们先前发现的腺泡气道中各向异性 3He 气体扩散的发现，我们开发并验证了采用超极化 3He 磁共振成像 (MRI) 的肺形态测量的创新成像技术，该技术为本研究提供了有关腺泡气道结构和空间分布的独特的体内定量信息。我们将 3He 形态测量数据与定量 CT 数据相结合，以获得肺实质（包括毛细血管的肺泡壁）和非实质（非毛细血管等）肺组织以及小传导气道疾病的独特信息。我们的具体目标侧重于建立腺泡和小气道结构改变与肺功能下降之间的定量关系：目标 1：识别和比较“健康”从不吸烟者和“健康”吸烟者中与衰老相关的肺功能进行性恶化的结构机制，并通过使用基于 MRI 的体内肺形态测量和 定量CT。 目标 2：通过使用基于 MRI 的体内肺形态测定和定量 CT 确定的定量指标，确定与吸烟相关的 COPD 相关的肺功能进行性恶化的结构机制，并将腺泡和小气道（“健康”的从不吸烟者和“健康”的吸烟者）中与年龄相关的结构变化的机制（“健康”的从不吸烟者和“健康”的吸烟者）与 COPD 引起的结构变化区分开来。 我们期望开发一种新方法来评估衰老和慢性阻塞性肺病对肺结构和功能的影响，提供对衰老、吸烟和肺气肿如何导致肺腺泡结构变化和相关肺功能恶化的新认识，并提出预防和治疗慢性阻塞性肺病这一主要公共卫生问题的新靶点。