Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations

Catarina Rua; Betty Raman; Christopher T Rodgers; Virginia F J Newcombe; Anne Manktelow; Doris A Chatfield; Stephen J Sawcer; Joanne G Outtrim; Victoria C Lupson; Emmanuel A Stamatakis; Guy B Williams; William T Clarke; Lin Qiu; Martyn Ezra; Rory McDonald; Stuart Clare; Mark Cassar; Stefan Neubauer; Karen D Ersche; Edward T Bullmore; David K Menon; Kyle Pattinson; James B Rowe

doi:10.1093/brain/awae215

Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations

Brain. 2024 Oct 7:awae215. doi: 10.1093/brain/awae215. Online ahead of print.

Authors

Catarina Rua^{1

2

3

4}, Betty Raman⁵, Christopher T Rodgers^{1

4}, Virginia F J Newcombe^{1

6}, Anne Manktelow⁶, Doris A Chatfield⁶, Stephen J Sawcer⁴, Joanne G Outtrim⁶, Victoria C Lupson¹, Emmanuel A Stamatakis^{1

4

6}, Guy B Williams^{1

4}, William T Clarke⁷, Lin Qiu⁷, Martyn Ezra⁷, Rory McDonald⁷, Stuart Clare⁷, Mark Cassar⁵, Stefan Neubauer⁵, Karen D Ersche^{8

9}, Edward T Bullmore^{1

8}, David K Menon^{1

6}, Kyle Pattinson⁷, James B Rowe^{2

10

11

12

5

7}

Affiliations

¹ Wolfson Brain Imaging Centre, University of Cambridge, Cambridge CB2 0QQ, UK.
² University of Cambridge Centre for Parkinson-plus, University of Cambridge, Cambridge CB2 0QQ, UK.
³ Invicro, Invicro London, Burlington Danes Building, Imperial College London, London W12 0NN, UK.
⁴ Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
⁵ Division of Cardiovascular Medicine, Radcliffe Department of Medicine and Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford OX3 9DU, UK.
⁶ Division of Anaesthesia, University of Cambridge, Cambridge CB2 0QQ, UK.
⁷ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DA, UK.
⁸ Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK.
⁹ Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Heidelberg 69115, Germany.
¹⁰ Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 7EF, UK.
¹¹ Cambridge NeuroCOVID Group, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
¹² CITIID-NIHR COVID-19 BioResource Collaboration, University of Cambridge, Cambridge CB2 0QQ, UK.

PMID: 39375207
DOI: 10.1093/brain/awae215

Abstract

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

Keywords: 7T MRI; brainstem; coronavirus disease of 2019; inflammation; quantitative susceptibility mapping.

Abstract

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