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

Abstract

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.

Two human brain systems micro-structurally associated with obesity

“…One limitation of this study is that data was collected at multiple centres and even though we used site as a nuisance regressor there might be unaccounted for non-linear effects. However Duff et al, 2022 showed that quantities derived from UK Biobank scans at different sites are reliable.…”

Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study

“…Although structural scans, as utilised in this study, are not thought to suffer from degradation of image quality as a result of head motion to the same extent as other modalities, it is worth acknowledging that such confounds could increase the risk of false positives (37,38). However, this study aimed to address this by excluding scans with signi cant motion artefact (39). Finally, the analysis of recovery trajectories was underpowered which limits interpretation, but there was evidence of a trend towards recovery that continued into the second year.…”

“…3T MRI protocols were harmonised and the published standardised protocol was consistent across sites (39). Speci c brain regions were selected based on extant literature a priori to analysis; the parahippocampal gyrus, entorhinal cortex, orbitofrontal cortex, anterior cingulate cortex, insula and superior temporal gyrus (7,47,48,49,50,51).…”

“…Speci c brain regions were selected based on extant literature a priori to analysis; the parahippocampal gyrus, entorhinal cortex, orbitofrontal cortex, anterior cingulate cortex, insula and superior temporal gyrus (7,47,48,49,50,51). MRI data were processed with FSL and Freesurfer, using the established UK Biobank pipeline, (37,39,52) modi ed for COVID-CNS, in order to produce biologically relevant metrics of brain structure and function -IDPs. IDPs from T1 and T2-FLAIR weighted MRI were obtained for global brain regions and for cortical regions as de ned by Desikan-Killiany parcellation.…”

Exploring the research landscape of COVID-19-induced olfactory dysfunction: A bibliometric study

“…In recent years, various tools and methods have been employed to evaluate OD in patients with COVID-19. For instance, Duff et al (2022) utilized brain magnetic resonance imaging (MRI) to assess the neuropsychiatric consequences of neocoronary pneumonia, demonstrating the high reliability of multiple imaging derived phenotypes (IDPs) in measuring the impact of SARS-CoV-2 infection on the brain through potential pathogenic mechanisms. Melkumyan et al (2022) conducted a cross-sectional study that analyzed the sensitivity to olfaction and trigeminal nerve-triggered olfaction, as well as the ability to distinguish between different odors, in patients recovering from neocoronary pneumonia and revealed pathological changes in olfactory and trigeminal perceptual abilities that result in OD.…”