Carina Graf¹, William T Clarke², Catarina Rua¹, Virginia FJ Newcombe^1,3, Victoria C Lupson¹, Anne Manktelow³, Doris A Chatfield¹, Stephen J Sawcer⁴, Joanne G Outtrim³, Karen Ersche⁵, Edward T Bullmore⁵, David K Menon³, Sarah L Finnegan⁶, Rory McDonald⁶, Stuart Clare⁶, Martyn Ezra⁶, Christopher T Rodgers¹, Kyle Pattinson⁶, and James B Rowe^4,5,7,8,9
1Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ²Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ³Divison of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom, ⁴Neurology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ⁵Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, ⁶Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ⁷Cambridge Centre for Frontotemporal Dementia, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ⁸MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom, ⁹on behalf of the Cambridge NeuroCOVID group and the CITIID-NIHR COVID-19 BioResource Collaboration (www.wbic.cam.ac.uk/neuro-covid/), Cambridge, United Kingdom

SARS-CoV-2 attacks the central nervous system. A particularly nasty symptom of COVID-19 is a feeling of breathlessness that can persist for months after acute infection has subsided (“long COVID”). Based on early MRI observations in hospitalised patients, we hypothesised that COVID-19 may cause inflammation or degeneration of the brainstem where the respiratory control centres are located, leading to these symptoms. In this study we develop a protocol for ¹H-MRS in the brainstem on two models of ultra-high field 7T MRI scanner. We show feasibility to profile brainstem neurochemistry in anticipation of a multi-site clinical study across the UK’s 7T centres.

Niu Shanshan¹, Xie Qing¹, Liao Jianwei¹, Li Yingqin¹, Qian Long², Zhang Yaqin¹, and Li Shaolin^1
1Department of Radiology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai,Guangdong, China, ²MR Research, GE Healthcare, Beijing, China

SARS‐CoV2 has been shown to cause central nervous system (CNS) damages. However, there have been few studies on neurological changes in recovered COVID-19 patients. In current study, we used DTI to assess the potential delayed damages in the CNS of the recovered COVID-19 patients caused by SARS-CoV2. Our results suggested that the microstructural integrity of white matter fibers is disrupted in recovered COVID-19 patients, which provided the evidence of CNS damages.

Wenjun Yu¹, Yijie Fang¹, Qikun Guo², Xiaojun Chen³, Wenhao Wu¹, Long Qian⁴, Taoyu Jia⁵, Kunwei Li¹, Chuan Huang⁶, Bing Wu⁴, and Shaolin Li^1
1Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China, ²The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, ³Radiology, The First Affiliated Hospital of Sun Yat-sen University, Zhuhai, China, ⁴MR Research, GE Healthcare, Beijing, Beijing, China, ⁵The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China, ⁶Radiology, Stony Brook Medicine, Stony Brook, New York, NY, United States

Liver injuries have been reported with strong evidence in COVID-19 patients.  Whether these disturbances are presented in patients recovered from COVID-19 is still unknown. Totally 31 COVID-19 recovered patients were collected. And 37 sex- and age-matched normal controls (NC) were were further recruited. MR imaging was performed using a 3.0T scanner with T1mapping, R2* mapping and proton density fat fraction (PDFF) for all the patients. Abnormal liver T1 and PDFF values, which may be associated with subclinical renal injury due to COVID-19.

Sichen Ludwig Zhao^1,2, Jay A Gottfried², John A Detre², and M Dylan Tisdall^3
1Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States, ²Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ³Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

The olfactory bulbs (OBs) and tracts transmit odor information from the nose to the brain and plays a key role in learning, memory, and emotion. In vivo imaging of the human olfactory bulbs (OBs) is inherently challenging due to their limited size and high susceptibility gradients at the basal frontal lobes. We compare three sequences (T2 SPACE, CISS, and T1-weighted PETRA) to produce the highest-resolution (440um) structural images of the human olfactory bulb at 3 T. We demonstrate that these images offer robust visualization of the olfactory bulbs and tracts that projects to the medial temporal lobes.

J. Jean Chen^1,2, Jordan A. Chad^1,2, Xiang Ji³, Bradley J. Macintosh^1,3, Asaf Gilboa^2,4, Eugenie Roudaia², Allison Sekuler^2,4, Benjamin Lam³, Chris Heyn³, Sandra E. Black³, and Simon J. Graham^1,3
1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada, ³Hurvitz Brain Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ⁴Department of Psychology, University of Toronto, Toronto, ON, Canada

The impact of COVID19 on the brain’s microstructural integrity is still unclear.  In this study, we study self-isolated COVID19 patients using diffusion-tensor and free-water imaging, based on single- and multi-shell acquisitions, respectively. We demonstrate reduced mean diffusivity and free water in both grey and white matter of patients in regions associated with vision and olfaction. At 3-month follow-up, microstructural abnormalities in patients appear to persist, and involve more brain regions, including parts of the default-mode network. Our results support the existence of measurable long-term, evolving brain deficits due to COVID19. 

Yijie Fang¹, Wenjun Yu¹, Long Qian², Chuan Huang³, and Shaolin Li^1
1The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China, ²MR Research, GE Healthcare, Beijing, China, ³Stony Brook Medicine, Stony Brook, New York, NY, United States

Renal injury has been commonly observed in patients with COVID-19. The effect of the virus on kidneys in COVID-19 recovered patients remains unclear. Thirty-seven COVID-19 recovered patients were Prospectively collected. And 37 sex- and age-matched normal controls (NC) were enrolled. T1 mapping, T2 mapping, BOLD and IVIM for each participant were acquired using 3.0T MRI. The COVID-19 recovered patients demonstrated abnormal renal T1 and T2 and R2* values, which may be associated with subclinical renal injury due to COVID-19.

James T. Grist^1,2,3, Mitch Chen³, Guilhem J. Collier⁴, Emily Fraser⁵, Ling-Pei Ho^5,6, and Jim M. Wild^4
1Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom, ²Centre for Magnetic Resonance, University of Oxford, Oxford, United Kingdom, ³Radiology, Oxford NHS Foundation Trust, Oxford, United Kingdom, ⁴POLARIS, University of Sheffield, Sheffield, United Kingdom, ⁵Oxford Interstitial Lung Disease Service, Oxford NHS Foundation Trust, Oxford, United Kingdom, ⁶MRC Human Immunology Unit, University of Oxford, Oxford, United Kingdom

Test

Simon J Graham¹, J Jean Chen², Asaf Gilboa², Brad J Macintosh³, Allison B Sekuler², Sandra E Black³, Jordan A Chad², Ivy Cheng⁴, Rob Fowler⁴, Fuqiang Gao³, Maged Goubran³, Chinthaka (Chris) Heyn¹, Aravinthan (Arv) Jegatheesan¹, Xiang (Patrick) Ji³, Ben Lam³, Mario Masellis³, Jennifer S Rabin³, and Eugenie Roudaia^2
1Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada, ²Rotman Research Institute, Baycrest, Toronto, ON, Canada, ³Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada, ⁴Evaluative Clinical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada

NEUROCOVID19 is a longitudinal observational study to characterize the impact of the SARS-COV-2 virus on brain anatomy and function in individuals who are no longer infectious, using an extensive MRI protocol. Novel aspects include imaging of COVID-19 survivors who either self-isolated or were hospitalized, and control individuals who had cold or flu-like symptoms but tested negative for the virus. Breath-hold ultra-short TE imaging of the lung is also included to study brain-lung relationships. This report describes the study design and initial anatomical findings of the recruited participants (3 hospitalized and 23 self-isolated COVID-19 participants, 11 controls at abstract submission).

Christine S W Law¹, Patricia S Lan², and Gary H Glover^2
1Stanford University, Palo Alto, CA, United States, ²Stanford University, Stanford, CA, United States

The widespread incidence of infection from the novel coronavirus SARS-CoV-2 has prompted many research MRI facilities to require scan subjects to wear masks during scanning in order to diminish the risk of virus transmission. Wearing an efficacious mask will mix some expired air with fresh air, and lead to increased carbon dioxide concentration [CO2] in inspired air. The question we approached is: Since CO2 is a potent vasodilator, does this elevation in [CO2] alter functional MRI (fMRI)?

Tuneesh K. Ranota¹, Hacene Serrai², David G. McCormack³, Grace Parraga^1,4,5, and Alexei Ouriadov^1,2,6
1School of Biomedical Engineering, Faculty of Engineering, The University of Western Ontario, London, ON, Canada, ²Department of Physics and Astronomy, The University of Western Ontario, London, ON, Canada, ³Division of Respirology, Department of Medicine, The University of Western Ontario, London, ON, Canada, ⁴Robarts Research Institute, London, ON, Canada, ⁵Department of Medical Biophysics, The University of Western Ontario, London, ON, Canada, ⁶Lawson Health Research Institute, London, ON, Canada

Hyperpolarized ¹²⁹Xe gas lung MRI is an efficient technique used to investigate and assess pulmonary diseases.  To improve the performance of ¹²⁹Xe MRI in lung imaging a method for high-resolution 3D static ventilation images using FGRE combined with the key-hole method in a single breath-hold, was proposed. This technique acquires high-resolution ¹²⁹Xe 3D static ventilation isotropic-voxel images from the COVID-19 survivors in a single breath-hold.  The SNR of the images allowed for the analysis of VDP. This study confirms the feasibility of using isotropic-voxel acquisition sequence in a single breath-hold MRI to study the effects of COVID-19 on the lungs.

Arthur Harrison¹, Galina E Pavlovskaya^1,2, Thomas Meersmann¹, Olga S Pavlova^3,4, Alexander Makurenkov⁴, Yury A Pirogov⁴, and Nikolay V Anisimov^3,4
1SPMIC/Medicine, University of Nottingham, Nottingham, United Kingdom, ²2Nottingham NIHR Biomedical Research Centre, Nottingham, United Kingdom, ³Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russian Federation, ⁴Faculty of Physics, Lomonosov Moscow State University, Moscow, Russian Federation

The ability to visualise non-invasively impaired lung ventilation and perfusion caused by lung scarring is important in monitoring recovery of Covid-19 survivors. The hp Xenon-129 imaging modality is currently approved for clinical use in the UK only, however, it has been shown recently that 1H PREFUL methodology can be used to visualise lung perfusion and ventilation in health and disease at 3T whole body scanners. However, 3T scanners may not be available for healthcare in countries with low and middle income,  hence PREFUL at 0.5T was used to assess lung ventilation and perfusion in health and Covid-19 disease.

Minhua Yu¹, Weiyin Vivian Liu², Qunfeng Wang³, Dan Xu¹, Yumin Liu³, and Haibo Xu^1
1Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China, ²MR Research, GE Healthcare, Beijing, China, ³Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China

This study aims to investigate the cerebral microstructural alteration of follow-up recovered COVID-19 (rCOVID-19) patients and explore the corrections of symptoms and microstructure changes. Decreased axial kurtosis (K_ax), radial kurtosis (K_rad), mean kurtosis (K_mean), mean kurtosis tensor (KT_mean) and increased fractional anisotropy (FA) in several brain regions of rCOVID-19 patients indicated demyelination and increased cell membrane permeability of cerebral cortex. Hyposmia was negatively correlated with K_mean and K_rad in right anterior cingulum of rCOVID-19 patients, partly explaining the residual olfactory impairment several months after recovery. DKI metrics can help reveal microstructural changes of CNS for rCOVID-19 patients.

Claudia A.M. Gandini Wheeler-Kingshott^1,2,3, Marios C. Yiannakas¹, Janine Makaronidis^4,5,6, Ferran Prados^7,8, Baris Kanber⁷, Bhavana S. Solanky¹, Marco Battiston¹, Jed Wingrove⁴, Francesco Grussu^1,7,9, Gloria Castellazzi^10,11, Jonathan Stutters¹, James McStravick¹, Anita Karsa¹², Rebecca Samson¹, Karin Shmueli¹², Xavier Golay¹³, Geoff J. M. Parker^1,7, Daniel C. Alexander⁷, Yael Hacohen¹, Egidio D'Angelo^2,3, Frederik Barkhof^13,14, Carmen Tur^1,15, Louis Grandjean¹⁶, Olga Ciccarelli¹, and Rachel L. Batterham^4,5,6
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, United Kingdom, ²Department of Brain & Behavioural Sciences, University of Pavia, Pavia, Italy, ³Brain Connectivity Center Research Department, IRCCS Mondino Foundation, Pavia, Italy, ⁴UCL Centre for Obesity Research, Division of Medicine, University College London (UCL), London, United Kingdom, ⁵Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital (UCLH), London, United Kingdom, ⁶National Institute of Health Research, UCLH Biomedical Research Centre, London, United Kingdom, ⁷Centre for Medical Image Computing, University College London (UCL), London, United Kingdom, ⁸E-Health Center, Universitat Oberta de Catalunya, Barcelona, Spain, ⁹Radiomics Group, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, ¹⁰IRCCS Mondino Foundation, Pavia, Italy, ¹¹Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy, ¹²Department of Medical Physics & Biomedical Engineering, University College London (UCL), London, United Kingdom, ¹³Department of Brain Repair & Rehabilitation, University College London (UCL), London, United Kingdom, ¹⁴Radiology, VU Medical Centre Amsterdam, Amsterdam, Netherlands, ¹⁵Neurology-Neuroimmunology Department, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, ¹⁶Department of Infection, Inflammation and Immunity, Institute of Child Health, University College London (UCL), London, United Kingdom

COVID-19 has now been associated with neurological symptoms, but the pathogenesis of such symptoms is unknown. Advanced quantitative MRI can provide information on alterations of brain tissue properties beyond clinically identifiable lesions. We developed a novel comprehensive scanning protocol and highly automated analysis pipeline to compare brain structure and function in people who were exposed to SARS-COV-2 infection against people who were not. Initial findings indicate that COVID-19 alters white matter microstructure and brain metabolism. 

Yaping Wu¹, Xianchang Zhang², Yu Shen¹, Yan Bai¹, Wei Wei¹, Congyu Liao³, and Meiyun Wang^1
1Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, China, ²MR Collaboration, Siemens Healthcare Ltd., Beijing, China, ³Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

This study investigated the utility of magnetic resonance fingerprinting (MRF) to detect potential brain changes in recovered COVID-19 patients. MRF T1 and T2 maps of the brains of 8 recovered COVID-19 patients and 8 volunteers were non-linearly normalized into the MNI space to explore the differences between the groups using whole-brain analysis. COVID-19 patients had significantly lower T1 and T2 values in the left superior temporal gyrus, near the hub for the olfaction and gustation systems, and other brain areas. Our findings suggest that SARS-CoV-2 may widely affect the neurological system, and the effect persisted after more than two months.

Akila Weerasekera^1,2, Otto Rapalino¹, Sarah J Moum¹, Katharina Eikermann-Haerter¹, Brian Edlow³, David Fischer¹, Angel Torrado-Carvajal^1,4, Marco L Loggia¹, Shibani Mukerji³, Pamela L Schaefer¹, Ramon Gilberto Gonzalez¹, Michael Lev¹, and Eva-Maria Ratai^1
1Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ²2A. A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ³Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ⁴Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain

Here we report for the first time metabolic abnormalities in white matter lesions of COVID-19 patients using MR-spectroscopic imaging. The study compares metabolic changes in COVID-19 patients to those seen in other encephalopathies and a normal control case. Findings include NAA reduction indicating neuronal injury/loss, and choline and myo-inositol elevation indicating demyelination and neuroinflammation, respectively. One COVID-19 patient exhibited pronounced lactate elevation consistent with "silent hypoxia". Other factors may be involved considering the degree of metabolic changes seen in these patients when compared to other COVID-19 cases without similar white matter changes as well as other white matter disorders. 

Xie Qing¹, Niu Shanshan¹, Liao Jianwei¹, Li Yingqin¹, Qian Long², Zhang Yaqin¹, and Li Shaolin^1
1Department of Radiology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China, ²MR Research, GE Healthcare, Beijing, China

Increasing evidences support that SARS-CoV-2 can invade the central nervous system (CNS) and damage neuronal cells. However, there is no study to unravel the brain microstructural changes associated with SARS-CoV-2. Synthetic MRI provides T1 and T2 mapping, which could quantitatively evaluate the tissue microstructures. In current study, our goal is to assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. Our results indicated that the microstructure component of gray matter is disrupted in recovered COVID-19 patients, which provided the evidence of CNS damages. 

Guilhem J Collier¹, Jody Bray¹, Ho-Fung Chan¹, Paul J.C. Hughes¹, James A Eaden¹, Laurie J Smith¹, Helen Marshall¹, David J Capener¹, Leanne Armstrong¹, Alberto M Biancardi¹, Madhwesha R Rao¹, Graham Norquay¹, Oliver Rodgers¹, Andy J Swift¹, Smitha Rajaram², Fergus Gleeson³, James T Grist³, Gary H Mills⁴, James Meiring², Lisa Watson², Paul J Collini⁴, Roger Thompson⁴, Rod Lawson², and Jim M Wild^1
1POLARIS, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom, ²Sheffield teaching hospitals, NHS Foundation TRUST, Sheffield, United Kingdom, ³Department of Radiology, Oxford NHS Foundation Trust, Oxford, United Kingdom, ⁴Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom

We assessed the sensitivity of a comprehensive multi-nuclear lung function-structure imaging protocol to acute changes in the lungs of patients admitted to hospital with COVID-19 lung infection. Dissolved ¹²⁹Xe spectroscopic imaging and DCE ¹H perfusion MRI indicate impaired gas transfer related to diffusion and microvascular perfusion limitation, whilst ¹²⁹Xe ventilation MRI and ¹²⁹Xe DWI indicate fairly homogenous lung ventilation and airway microstructure, apart from in areas showing clear structural abnormality on UTE/ZTE imaging (residual ground glass opacity or consolidation). The findings provide quantitative regional insight in to why patients suffer from severe breathlessness despite their lung ventilation appearing near normal.

Alexander Lin¹, Min Zhou², Huijun Liao¹, Eduardo Coello¹, and Jong-Woo Lee^3
1Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, ²Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ³Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States

The goal of this study was to measure brain metabolites in patients recovered from COVID-19 to examine the chronic effects of COVID, also known as long COVID, which have been shown to have neurological effects.  Spectroscopy in the cingulate gyrus revealed increased choline and glutamate/glutamine which may be reflective of neuroinflammatory changes due to long COVID.

Helma Heidari^1,2, Stephanie Handsor³, Koula Pantazopoulos⁴, Lauryn Richardson⁴, Kristy Coleman⁴, Michael Silverman⁵, Erin Spicer³, Stephen Pasternak^4,6, Luciano Sposato⁶, Doug Fraser⁷, Anthony Tang⁸, Ravi S. Menon^1,2, Corey Baron^1,2, Michael Jurkiewicz⁹, Elizabeth Finger^4,6, Marko Mrkobrada³, Megan Devlin³, and Robert Bartha^1,2
1Robarts research Institute, London, ON, Canada, ²Medical Biophysics, The University of Western Ontario, London, ON, Canada, ³Internal Medicine, The University of Western Ontario, London, ON, Canada, ⁴Parkwood Institute, London, ON, Canada, ⁵Infectious Diseases, The University of Western Ontario, London, ON, Canada, ⁶Clinical Neurological Sciences, The University of Western Ontario, London, ON, Canada, ⁷Paediatric Critical Care, The University of Western Ontario, London, ON, Canada, ⁸Medicine, The University of Western Ontario, London, ON, Canada, ⁹Medical Imaging, The University of Western Ontario, London, ON, Canada

Evidences support that the new SARS-Cov2 virus has neurological consequences in patients. Using the high resolution and sensitivity of 7T MRI, this study will determine if prolonged cognitive and neurological symptoms in patients recovered from COVID-19 illness are related to brain imaging findings. Six patients with neurological symptoms during their illness and with no respiratory symptoms for at least one month have been recruited to date.  Advanced 7T MRI including susceptibility weighted imaging, diffusion tensor imaging, and chemical exchange saturation transfer imaging has been successfully acquired in four subjects with patient recruitment ongoing.