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.

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.

Bitbox: A Cloud-based data sharing solution for medical images.

With the modernization and digitisation of the healthcare system, the need for exchanging medical data has become increasingly compelling. Biomedical imaging has been no exception, where the gathering of medical imaging acquisitions from multi-site collaborations have enabled to reach data sizes never imaginable until few years ago. Usually, medical imaging data have very large volume and diverse complexity, requiring bespoken transfer systems that protect personal information as well as data integrity. Despite many digital innovations, there are still technical and regulatory bottlenecks that make biomedical imaging data exchange challenging. Here we present Bitbox, a web-based application which provides a reliable yet straightforward service to securely exchange medical imaging data. With Bitbox, both imaging and non-imaging data of any type can be transferred from any external and independent site into a centralized server. A showcase of the system will be illustrated for the COVID-19 Clinical Neuroscience Study (COVID-CNS) project, a UK-wide experimental medicine study to investigate the neurological and neuropsychiatric effects of COVID-19 infections in hundreds of patients.

Estimating required ‘lockdown’ cycles before immunity to SARS-CoV-2: model-based analyses of susceptible population sizes, ‘S0’, in seven European countries, including the UK and Ireland [version 1;peer review: awaiting peer review]

Background: Following stringent social distancing measures, some European countries are beginning to report a slowed or negative rate of growth of daily case numbers testing positive for the novel coronavirus. The notion that the first wave of infection is close to its peak begs the question of whether future peaks or ‘second waves’ are likely. We sought to determine the current size of the effective (i.e. susceptible) population for seven European countries—to estimate immunity levels following this first wave. Methods: We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model, and second a partially observable Markov Decision Process or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (‘S0’), as well as epidemic parameters. Results: Both models recapitulated the dynamics of transmissions and disease as given by case and death rates. Crucially, maximum a posteriori estimates of S0 for each country indicated effective population sizes of below 20% (of total population size), under both the continuous time and HMM models. Using a Bayesian weighted average across all seven countries and both models, we estimated that 6.4% of the total population would be immune. From the two models, the maximum percentage of the effective population was estimated at 19.6% of the total population for the UK, 16.7% for Ireland, 11.4% for Italy, 12.8% for Spain, 18.8% for France, 4.7% for Germany and 12.9% for Switzerland. Conclusion: Our results indicate that after the current wave, a large proportion of the total population will remain without immunity.

A simulated single ventilator/dual patient ventilation strategy for acute respiratory distress syndrome during the COVID-19 pandemic.

The potential for acute shortages of ventilators at the peak of the COVID-19 pandemic has raised the possibility of needing to support two patients from a single ventilator. To provide a system for understanding and prototyping designs, we have developed a mathematical model of two patients supported by a mechanical ventilator. We propose a standard set-up where we simulate the introduction of T-splitters to supply air to two patients and a modified set-up where we introduce a variable resistance in each inhalation pathway and one-way valves in each exhalation pathway. Using the standard set-up, we demonstrate that ventilating two patients with mismatched lung compliances from a single ventilator will lead to clinically significant reductions in tidal volume in the patient with the lowest respiratory compliance. Using the modified set-up, we demonstrate that it could be possible to achieve the same tidal volumes in two patients with mismatched lung compliances, and we show that the tidal volume of one patient can be manipulated independently of the other. The results indicate that, with appropriate modifications, two patients could be supported from a single ventilator with independent control of tidal volumes.