Assessment of lung alveolar development in childhood and adolescence using 3-helium magnetic resonance

The major functional units of the lung called alveoli, are located in the periphery of the lung. Despite their functional importance, it has been difficult to evaluate their structure and development. Until the advent of 3-Helium magnetic resonance (3HeMR), it was not possible to directly assess peripheral lung structure in a living individual. When this study commenced, the prevailing hypothesis was that human alveolarization was complete by 3 years. It was believed that preterm birth would lead to persisting alveolar damage. The role of other factors affecting human lung development were not clearly understood. In this work, I describe the use of 3HeMR to : 1. Examine the current hypothesis regarding normal alveolar development, 2. Determine whether birth at very preterm gestation leads to long-term alveolar damage and 3. Evaluate factors affecting human alveolar development. First, we determined alveolar size using 3HeMR in healthy subjects aged 7 to 21 years. Alveolar dimensions did not increase by the expected rate over this age range, despite lung capacity increasing nearly fourfold. The only plausible explanation is new alveoli forming throughout the period of lung growth. Then, we compared alveolar size between children born very prematurely (<32 weeks gestation), including survivors of neonatal chronic lung disease (CLD) with term born children and children born mildly preterm (33-36 weeks gestation). Alveolar dimensions were nearly identical suggesting alveolar catch up growth in the very preterm groups. In the third part of the study, we investigated the relationship between various risk factors and alveolar dimensions. Exposure to environmental tobacco smoke (ETS) was found to be consistently associated with larger alveoli, suggesting its detrimental effect on alveolar development. Our results imply that developing lungs have the potential to recover from early life insults. Conversely, the window for adverse environmental exposures to affect alveolar development may be wider than previously believed.