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

项目摘要/摘要 慢性肺病是致残和死亡的主要原因，很大程度上是因为它通常是在 已经发生了不可逆转的肺损伤。美国肺脏协会(ALA)肺健康队列(LHC)是 由NHLBI资助，以阐明与肺健康峰值和早期肺偏离相关的因素 可能发展为慢性肺部疾病的健康。大型强子对撞机将收集肺活量、鼻上皮 转录组和CT成像，以及全面的环境暴露、社会行为、健康、 在全国范围内对4000名年龄在25岁到35岁之间的年轻人进行了调查。尽管 这些丰富的信息令人担忧，大型强子对撞机疾病的早期阶段可能没有被发现， 由于早期疾病被认为起源于最远端的空域，LHC测试方案所在的区域 无法探测。为此，我们建议对肺健康队列进行一项辅助研究，我们的目标是 收集部分大型强子对撞机参与者的超极化129Xe磁共振。超极化129Xe磁共振成像(Xe-MRI)是一种新型的核磁共振成像技术 可用于测量肺结构和功能的成像技术。具体地说，可以使用Xe-MRI 成像呼吸道功能(“通风成像”)、肺泡空隙大小(“弥散成像”)和肺气量 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 在肺部最小的空隙中发挥作用。因此，Xe-MRI有望对最早的 这是对肺部疾病表现形式的补充，从而补充了大型强子对撞机正在获取的信息。在这 在子研究中，我们将使用Xe-MRI对260名LHC参与者进行成像，这些参与者分布在父母参与的17个站点中的6个 强子对撞机。在目标1中，我们将使用Xe-mri扩散成像来评估LHC的肺微结构。 肺功能正常(预计85%)低的受试者。通过这样做，我们的目标是确定结构 偏离肺健康峰值的依据。在目标2中，我们将使用Xe-MRI来评估肺结构和 有呼吸道症状(咳嗽、咳痰、喘息、呼吸困难)的大型强子对撞机参与者的功能。通过这样做，我们 目的阐明呼吸系统症状的结构和功能决定因素 临床指标如肺活量测定和CT成像。这项研究的预期结果是确定 与临床可测量的峰值偏差相关的结构和功能异常 肺健康(肺功能正常程度低和呼吸道症状)。这些信息最终将提供一个 对这些人来说是可治疗的目标。此外，由于大型强子对撞机打算纵向跟踪参与者，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，我们使用Xe-MRI测量年轻成年人肺结构和功能的能力 肺健康高峰期的年龄有助于在不可逆转的肺发展之前识别疾病。 损害，使临床医生从缓解慢性肺部疾病过渡到预防慢性肺部疾病。

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.