Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.
Creators: name: Duff, Eugene
name: Zelaya, Fernando
name: Almagro, Fidel Alfaro
name: Miller, Karla L
name: Martin, Naomi
name: Nichols, Thomas E
name: Taschler, Bernd
name: Griffanti, Ludovica
name: Arthofer, Christoph
name: Douaud, Gwenaëlle
name: Wang, Chaoyue
name: Okell, Thomas W
name: Bethlehem, Richard AI
name: Eickel, Klaus
name: Günther, Matthias
name: Menon, David K
name: Williams, Guy
name: Facer, Bethany
name: Lythgoe, David J
name: Dell'Acqua, Flavio
name: Wood, Greta K
name: Williams, Steven CR
name: Houston, Gavin
name: Keller, Simon S
name: Holden, Catherine
name: Hartmann, Monika
name: George, Lily
name: Breen, Gerome
name: Michael, Benedict D
name: Jezzard, Peter
name: Smith, Stephen M
name: Bullmore, Edward T
name: COVID-CNS Consortium
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Research Article
Medicine and health sciences
Research and analysis methods
Biology and life sciences

description: Acknowledgements: We thank the volunteers who participated in the travelling heads study and the radiography staff who collected data at all four sites. We thank Fraunhofer MEVIS, Bremen, Germany, for provision of the Siemens 3D-GRASE ASL sequence.
description: Funder: National Institute for Health Research; funder-id: http://dx.doi.org/10.13039/501100000272
description: Funder: Addenbrooke’s Charitable Trust, Cambridge University Hospitals; funder-id: http://dx.doi.org/10.13039/501100002927
description: Funder: NIHR Oxford Biomedical Research Centre; funder-id: http://dx.doi.org/10.13039/501100013373
description: INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study.