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 慢性肺病是导致残疾和死亡的主要原因，这在很大程度上是因为它通常是在 发生了不可逆的肺损伤。美国肺脏协会（ALA）肺部健康队列（LHC） 由NHLBI资助，旨在阐明与肺部健康峰值和早期肺部偏离相关的因素。 可能发展为慢性肺病的健康状况。大型强子对撞机将收集肺功能，鼻上皮细胞 转录组和CT成像，以及全面的环境暴露，社会行为，健身， 和居住历史在全国范围内的4000名年轻人之间的年龄在25岁和35岁。尽管 这些丰富的信息，令人担心的是，疾病的最早阶段可能在LHC中未被发现， 因为早期疾病被认为起源于最远端的空气空间，LHC测试方案是 无法探测。为此，我们建议对肺部健康队列进行一项辅助研究， 收集LHC参与者子集中的超极化129 MRI。超极化129磁共振成像（Xe-MRI）是一种新的 可以用于测量肺结构和功能的成像技术。具体而言，可以使用Xe-MRI 成像气道功能（“通气成像”）、肺泡-空气空间大小（“扩散成像”）和肺气体 气体交换成像（Gas Exchange Imaging）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，预计Xe-MRI对最早的 这是肺部疾病的表现，从而补充了LHC获得的信息。在这 在子研究中，我们将使用Xe-MRI对母研究中涉及的17个研究中心中的6个研究中心的260名LHC参与者进行成像 LHC目的1：利用Xe-MRI弥散成像技术对LHC中肺组织的显微结构进行评价 肺功能正常（<85%预测值）。通过这样做，我们的目标是确定结构 与肺部健康峰值的偏差。在目标2中，我们将使用Xe-MRI评估肺结构， LHC参与者的呼吸道症状（咳嗽、咳痰、喘息、呼吸困难）。通过这样做，我们 目的是阐明呼吸道症状的结构和功能决定因素，这些决定因素很难用 临床指标，如肺量测定和CT成像。本研究的预期结果是确定 与临床可测量的峰值偏离相关的结构和功能异常 肺健康（正常肺功能低下和呼吸道症状）。这些信息最终将提供一个 可治疗的目标。此外，由于LHC打算纵向跟踪参与者，我们 我希望能够将早期结构和功能异常与慢性肺疾病的发展联系起来， 疾病最后，我们使用Xe-MRI测量年轻人肺结构和功能的能力， 肺健康高峰期的年龄将能够在不可逆肺疾病发展之前识别疾病 损害，使临床医生从缓解过渡到预防慢性肺部疾病。