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

Marta Tibiletti, James A. Eaden, Josephine H. Naish, Paul J.c. Hughes, John C. Waterton, Matthew J. Heaton, Nazia Chaudhuri, Sarah Skeoch, Ian N. Bruce, Stephen Bianchi, Jim M. Wild, Geoff J.m. Parker

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PURPOSE: 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.

STUDY TYPE: Prospective longitudinal.

POPULATION: 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.

FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T, including inversion recovery T 1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing.

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

STATISTICAL TEST: 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.

RESULTS: 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.

DATA CONCLUSION: 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.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalJournal of Magnetic Resonance Imaging
Early online date15 Oct 2022
Publication statusPublished online - 15 Oct 2022

Bibliographical note

The research leading to these results received funding from the Innovative Medicines Initiatives 2 Joint Undertaking under grant agreement No 116106. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This work was also supported by the National Institute of Health Research (RP-R3-12-027), Medical Research Council (MR/M008894/1) and GlaxoSmithKline (PJCH:BIDS3000032592).


  • Hyperpolarised gas MRI
  • Oxygen enhanced MRI
  • Lung MRI
  • Interstitial lung disease


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