Image Phenotyping of Preterm-Born Children Using Hyperpolarized 129Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout

Abstract

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized ¹²⁹Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (⩽34 weeks' gestation) and 19 term-born control subjects (⩾37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV₁ < lower limit of normal [LLN] and FEV₁/FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (FEV₁ < LLN and FEV₁/FVC ⩾ LLN), preterm-(FEV₁ ⩾ LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from ¹²⁹Xe ventilation MRI and SF₆ MBW. Alveolar microstructural dimensions were derived from ¹²⁹Xe diffusion-weighted MRI. Measurements and Main Results: ¹²⁹Xe ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean ¹²⁹Xe apparent diffusion coefficient, ¹²⁹Xe apparent diffusion coefficient interquartile range, and ¹²⁹Xe mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

Keywords: bronchopulmonary dysplasia; hyperpolarized 129Xe MRI; lung function; lung microstructure; prematurity-associated lung disease.