Hyperpolarized ¹²⁹Xe magnetic resonance spectroscopy in a rat model of bronchopulmonary dysplasia

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) ¹²⁹Xe gas measured with HP ¹²⁹Xe magnetic resonance spectroscopy (MRS). To investigate HP ¹²⁹Xe MRS as a tool for noninvasive characterization of pulmonary microstructural and functional changes in vivo, HP ¹²⁹Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (L_m), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (t), were compared with airspace mean axis length and area density (MAL and ρ_A) and percentage area of tissue and air (PTA and PAA) from histology. L_m was significantly larger in the exposed rats (P = 0.003) and correlated with MAL, ρ_A, PTA, and PAA (0.59<|ρ|<0.66 and P < 0.05). Observed increase in HCT (P = 0.012) and changes in t are also discussed. These findings support the use of HP ¹²⁹Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.