Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1 H and 129 Xe lung MRI

  1. Laura C Saunders
  2. Guilhem J Collier
  3. Ho-Fung Chan
  4. Paul J C Hughes
  5. Laurie J Smith
  6. James Watson
  7. James Meiring
  8. Zoë Gabriel
  9. Thomas Newman
  10. Megan Plowright
  11. Phillip Wade
  12. James A Eaden
  13. Jody Bray
  14. Helen Marshall
  15. David J Capener
  16. Leanne Armstrong
  17. Jennifer Rodgers
  18. Martin Brook
  19. Alberto M Biancardi
  20. Madhwesha R Rao
  21. Graham Norquay
  22. Oliver Rodgers
  23. Ryan Munro
  24. James E Ball
  25. Neil J Stewart
  26. Allan Lawrie
  27. Gisli Jenkins
  28. James Grist
  29. Fergus Gleeson
  30. Rolf F. Schulte
  31. Kevin M Johnson
  32. Frederick Wilson
  33. Anthony Cahn
  34. Andrew J Swift
  35. Smitha Rajaram
  36. Gary H Mills
  37. Lisa Watson
  38. Paul J Collini
  39. Rod Lawson
  40. A A Roger Thompson
  41. Jim M Wild

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Abstract

Introduction

Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear.

Methods

Patients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary 1 H and 129 Xe MRI protocol at 6, 12, 25 and 51 weeks after hospital admission. The imaging protocol included: ultra-short echo time, dynamic contrast enhanced lung perfusion, 129 Xe lung ventilation, 129 Xe diffusion weighted and 129 Xe 3D spectroscopic imaging of gas exchange.

Results

9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 51 (n=8) weeks after hospital admission. Patients with signs of interstitial lung damage at 3 months were excluded from this study. At 6 weeks after hospital admission, patients demonstrated impaired 129 Xe gas transfer (RBC:M) but normal lung microstructure (ADC, Lm D ). Minor ventilation abnormalities present in four patients were largely resolved in the 6–25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 week follow up, significant improvements in 129 Xe gas transfer were observed compared to 6-week examinations, however 129 Xe gas transfer remained abnormally low at weeks 12, 25 and 51. Changes in 129 Xe gas transfer correlated significantly with changes in pulmonary blood volume and TL CO Z-score.

Conclusions

This study demonstrates that multinuclear MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Impairment of xenon transfer may indicate damage to the pulmonary microcirculation.

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  1. Version published to 10.1101/2022.04.06.22272747v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2022.04.06.22272747: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variable11 subjects from this previously published work were selected based on age and sex from a cohort of 23 whilst blinded to MRI metrics, such that the control cohort had a median age of 63 (40-70) years and were 27% female.
    Randomizationnot detected.
    BlindingMedian RBC:M, RBC:gas and M:gas for an age and sex matched control cohort were determined by retrospective analysis of a healthy cohort data set, with controls chosen based on age and sex whilst blinded to MRI metrics.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was performed using IBM SPSS Statistics 27
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A limitation of this study is that not all patients had DCE lung perfusion imaging. However, all patients with DCE data available showed an increase in regional pulmonary blood flow and volume between visits 1 and 2, despite only one having a substantial perfusion defect. This may indicate microvascular improvements at 12 weeks. The analysis of covariance between RBC:M and pulmonary blood volume, showed that an individuals’ increase in RBC:M was significantly and positively associated with an increase in pulmonary blood volume. This indicates that microvascular recovery may be partially driving changes in RBC:M in these patients. In parallel a concomitant reduction in M signal due to resolution of post-infection endothelial inflammation could contribute to the increase in RBC:M with time. The main limitation of this study is the relatively small number of participants which was largely due to the challenging nature of recruiting patients for scanning after a recent hospitalisation due to COVID-19. The numbers recruited limit correlations with symptoms, activity and lung function and also the statistical tests used to test for change. A potential source of bias in this study is that 5 patients who were potentially eligible for the study were excluded due to chest size exceeding the size of the xenon MRI coil. Previous data from age and sex matched healthy volunteer cohorts were included in this paper, to illustrate where metrics deviated from normal values. Age dependence of g...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.04.06.22272747v1 on medRxiv