Adapting the UK Biobank Brain Imaging Protocol and Analysis Pipeline for the C-MORE Multi-Organ Study of COVID-19 Survivors

  1. Ludovica Griffanti
  2. Betty Raman
  3. Fidel Alfaro-Almagro
  4. Nicola Filippini
  5. Mark Philip Cassar
  6. Fintan Sheerin
  7. Thomas W. Okell
  8. Flora A. Kennedy McConnell
  9. Michael A. Chappell
  10. Chaoyue Wang
  11. Christoph Arthofer
  12. Frederik J. Lange
  13. Jesper Andersson
  14. Clare E. Mackay
  15. Elizabeth M. Tunnicliffe
  16. Matthew Rowland
  17. Stefan Neubauer
  18. Karla L. Miller
  19. Peter Jezzard
  20. Stephen M. Smith

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Abstract

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the possible effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T 1 , T 2 -FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 min. The automated imaging pipeline derives 1,575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, IDPs related to atrophy, small vessel disease and olfactory bulbs were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed some group differences between recovered COVID-19 patients and controls, across severity groups, but not across anosmia groups. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in other large-scale studies. The protocol, pipeline code and data are openly available and will further contribute to the understanding of the medium to long-term effects of COVID-19.

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  1. Version published to 10.3389/fneur.2021.753284
  2. ScreenIT

    SciScore for 10.1101/2021.05.19.21257316: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was registered at ClinicalTrials.gov (NCT04510025) and approved in the United Kingdom by the North West Preston Research Ethics Committee (reference 20/NW/0235).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Image processing was largely based around tools from FSL (FMRIB Software Library)(Jenkinson et al., 2012).
    FMRIB
    suggested: (FSL, RRID:SCR_002823)
    For the FreeSurfer IDPs, the comparisons were based on the Desikan-Killiany-Tourville DKT (Klein and Tourville, 2012) atlas.
    FreeSurfer
    suggested: (FreeSurfer, RRID:SCR_001847)
    Statistical analyses were performed using SPSS Version 27.0 (IBM, Armonk, NY, USA).
    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:
    This exploratory study has several limitations. The sample size is relatively small and, due to the comparisons performed on a wide range of IDPs, the results do not survive correction for multiple comparison. Anosmia was not assessed at the time of scan but rather at admission. Group differences in brain IDPs between COVID subgroups could be related to the therapy used while in hospital and not specific to COVID-19 per se. In conclusion, we developed a brain MRI protocol and analysis pipeline that enable efficient yet comprehensive assessment of brain changes in COVID-19 patients, and could be used both as part of a multiorgan imaging study as well as standalone. The observed changes in the C-MORE study have provided early insights into the potential repercussions following infection. The C-MORE study included a limited number of previously hospitalised patients and focused on assessing medium-term damage, but has paved the way for more extensive and longitudinal studies that can take advantage of the protocol and analysis developed as part of this study. The follow-up phase of the C-MORE study is currently ongoing and aims to monitor the longitudinal trajectory of multiorgan health beyond the subacute phase. This multiorgan imaging protocol is also now being used in the ‘PHOSP-COVID Post-hospitalisation COVID-19’ study, a large UK-wide national consortium (N=616), and in the CONVALESCENCE study, a study of patients with Long COVID (N=800). This will allow for testing the re...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04510025RecruitingCapturing MultiORgan Effects of COVID-19

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.05.19.21257316v1 on medRxiv