Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

To compare imaging biomarkers from hyperpolarised ¹²⁹Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression.

Prospective longitudinal.

Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks.

MRI was performed at 1.5 T, including inversion recovery T₁ mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised ¹²⁹Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing.

Five ¹H MRI and two ¹²⁹Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements.

To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models.

The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with ¹²⁹Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. ¹²⁹Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits.

Neither ¹²⁹Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by ¹²⁹Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and ¹²⁹Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.