Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations
Year: 2024
Type: article
Study design: Observational Study
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.
Source: Brain
Authors: 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
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,831
Funders: National Institute on Handicapped Research, NHS Blood and Transplant, Wellcome Trust, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, University of Oxford, BHF Centre of Research Excellence, Oxford, Medical Research Council Canada, NIHR BioResource, Medical Research Council, NIHR Oxford Biomedical Research Centre, NIHR Cambridge Biomedical Research Centre, Cambridge Centre for Parkinson-Plus
Awards: G131530194, G1364545886, G139696651, Wellcome Centre for Integrative Neuroimaging, A new collaborative ultra-high field MRI facility for dementia and neuroscience research, G2493601830, G2537968379, G2792775314, Metabolic magnetic resonance imaging across the human heart, G3099948101, Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease., G370598735, Developing spatially resolved imaging of functional neurochemistry and cell- type specific microstructure in the living human brain, G3942270087, Bridging the gap: biophysical models of human frontotemporal lobar degeneration, G4214616087, G463160924, G4753630297, G5124570546, Decision making and dementia: from mechanisms to clinical trials, G6248927271, G6254238750, G639689439, G6641991021, Wellcome Centre for Integrative Neuroimaging, G7826725679, G7889748471, G8415457339, Wellcome Centre for Integrative Neuroimaging - extension, G8988971166
OpenAlex ID: W4403239792