Hyperpolarized 129Xe MRI to identify structural determinants of low lung function and respiratory symptoms in young adults from the Lung Health Cohort

超极化 129Xe MRI 用于识别肺健康队列中年轻人低肺功能和呼吸道症状的结构决定因素

• 批准号: 10639640
• 负责人: Peter James Niedbalski
• 金额: $ 89.43万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-16 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639640
• 关键词: Acceleration; Age; Air; Alveolar; Alveolar Duct; American Lung Association; Ancillary Study; Blood capillaries; Caring; Cessation of life; Chronic; Chronic lung disease; Clinical; Clinical Markers; Clinical Research; Cohort Studies; Complement; Coughing; Data; Defect; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Distal; Dyspnea; Elderly; Environmental Exposure; Foundations; Funding; Future; Gases; Goals; Image; Imaging Techniques; Impairment; Individual; Investigation; Ionizing radiation; Life; Link; Long COVID; Lung; Lung diseases; Magnetic Resonance Imaging; Maps; Measurable; Measurement; Measures; Membrane; Modeling; Nasal Epithelium; National Heart, Lung, and Blood Institute; Oranges; Outcome; Outcome Study; Parents; Participant; Patients; Physiological; Population; Populations at Risk; Predisposition; Prevention; Process; Protocols documentation; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Gas Exchange; Pulmonary function tests; Recommendation; Recording of previous events; Regimen; Research Personnel; Respiratory Signs and Symptoms; Risk Factors; Site; Smoker; Social Behavior; Spirometry; Sputum; Structural defect; Structure; Symptoms; Techniques; Testing; Therapeutic Intervention; Wheezing; Work; X-Ray Computed Tomography; Xenon; associated symptom; base; cohort; common symptom; disability; fitness; in vivo; insight; lung health; lung injury; multi-site trial; novel imaging technique; palliation; poor health outcome; pulmonary function; pulmonary function decline; respiratory; respiratory imaging; structural determinants; symptomatology; targeted treatment; transcriptome; ventilation; young adult

PROJECT SUMMARY/ABSTRACT Chronic lung disease is a leading cause of disability and death, in large part because it is often diagnosed after irreversible lung damage has occurred. The American Lung Association (ALA) Lung Health Cohort (LHC) was funded by NHLBI to elucidate factors associated with peak lung health and the early deviations from lung health that may progress to chronic lung disease. The LHC will be collecting spirometry, nasal epithelial transcriptome, and CT imaging, alongside comprehensive environmental exposure, socio-behavioral, fitness, and residential history in a nation-wide cohort of 4000 young adults between the ages of 25 and 35. Despite this wealth of information, there is concern that the earliest stages of disease may go undetected in the LHC, as early disease is thought to originate in the most distal airspaces, regions which the LHC testing regimen is unable to probe. To that end, we are proposing an ancillary study to the Lung Health Cohort in which we aim to collect hyperpolarized 129Xe MRI in a subset of LHC participants. Hyperpolarized 129Xe MRI (Xe-MRI) is a novel imaging technique that can be used to measure lung structure and function. Specifically, Xe-MRI can be used to image airway function (“ventilation imaging”), alveolar-airspace size (“diffusion imaging”), and pulmonary gas exchange (“gas exchange imaging”). Notably, these imaging techniques are able to prove structure and function in the smallest airspaces of the lungs. As such, Xe-MRI is expected to be sensitive to the earliest manifestations of pulmonary disease and thus complements the information being acquired by the LHC. In this sub-study, we will use Xe-MRI to image 260 LHC participants across 6 of the 17 sites involved in the parent LHC. In aim 1, we will use Xe-MRI diffusion imaging to assess the pulmonary microstructure in LHC participants with low normal (<85% predicted) lung function. By doing so, we aim to determine the structural basis of deviations from peak lung health. In aim 2, we will use Xe-MRI to assess pulmonary structure and function in LHC participants with respiratory symptoms (cough, sputum, wheeze, dyspnea). By doing so, we aim to elucidate structural and functional determinants of respiratory symptoms that are poorly explained by clinical markers such as spirometry and CT imaging. The expected outcome of this study is to identify structural and functional abnormalities that are associated with the clinically measurable deviations from peak lung health (low normal lung function and respiratory symptoms). Such information will ultimately provide a treatable target for these individuals. Moreover, as the LHC intends to follow participants longitudinally, we expect to be able to link early structural and functional abnormalities to the development of chronic lung disease. Ultimately, our ability to measure lung structure and function using Xe-MRI in young adults at the ages of peak lung health will enable the identification of disease prior to the development of irreversible lung damage, allowing clinicians to transition from palliation to prevention of chronic lung disease.

项目摘要/摘要 慢性肺病是造成混乱和死亡的主要原因，在很大程度上是因为经常在 发生了不可逆的肺部损伤。美国肺协会（ALA）肺健康队列（LHC）是 由NHLBI资助以阐明与肺峰健康和肺部早期出发有关的因素 可能发展为慢性肺部病的健康。 LHC将收集肺部上皮测量值 转录组和CT成像，以及全面的环境暴露，社会行为，健身， 以及居民在全国4000名25至35岁之间的全国人群中的历史。 有很多信息，人们担心疾病的最早阶段可能在LHC中未发现， 由于早期疾病被认为起源于最远端的空域，因此LHC测试方案为 无法探测。为此，我们向肺部健康队列提出了一项辅助研究，我们的目的是 在LHC参与者的一部分中收集超极化的129xE MRI。超极化129XE MRI（XE-MRI）是一种新颖 成像技术可用于测量肺结构和功能。具体而言，可以使用Xe-MRI 图像气道功能（“通风成像”），肺泡空间大小（“扩散成像”）和肺气气 交换（“气体交换成像”）。值得注意的是，这些成像技术能够证明结构和 在肺的最小空间中起作用。因此，Xe-MRI有望对最早的 肺部疾病的表现，从而完成了LHC获得的信息。在这个 子研究，我们将使用XE-MRI在涉及父母的17个站点中的6个中映像260个LHC参与者 LHC。在AIM 1中，我们将使用XE-MRI扩散成像来评估LHC中的肺微结构 正常（预测<85％）肺功能的参与者。通过这样做，我们旨在确定结构 偏离肺峰健康的基础。在AIM 2中，我们将使用Xe-MRI评估肺结构和 具有呼吸道症状的LHC参与者（咳嗽，痰，喘息，呼吸困难）的功能。这样，我们 旨在阐明呼吸道症状的结构和功能决定者，这些症状的解释很差 临床标记，例如肺活量法和CT成像。这项研究的预期结果是确定 与临床可测量的峰值出发有关的结构和功能异常 肺部健康（正常肺功能和呼吸道症状）。这些信息最终将提供 这些人的可治疗目标。而且，由于LHC打算纵向关注参与者，我们 期望能够将早期结构和功能异常与慢性肺的发展联系起来 疾病。最终，我们在年轻人中使用XE-MRI测量肺结构和功能的能力 肺部峰值健康的年龄将在发展不可逆的肺部发展之前鉴定出疾病 损害，允许临床医生从抑制过渡到预防慢性肺部疾病。