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

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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.