The COVID-19 pandemic has had a major impact on health care systems across the globe in a short period of time. There is a growing body of evidence surrounding the findings on hybrid imaging with FDG-PET/CT, and this case highlights the importance of molecular imaging in better understanding of the biomarkers of the disease which ultimately determine the success in building a model to predict the disease severity and monitoring the response to treatment

Doran, S

Fraioli, F

Nasoodi, A

O'Neill, H

English

UCL Discovery

CASE REPORT Open AccessA twisted tale-radiological imaging featuresof COVID-19 on 18F-FDG PET/CTHazel O’Neill1, Simon Doran1, Francesco Fraioli2 and Afshin Nasoodi1** Correspondence: afshin.nasoodi@gmail.com1Department of Radiology, St.James’s Hospital, D08 X4RX Dublin,IrelandFull list of author information isavailable at the end of the articleAbstractThe COVID-19 pandemic has had a major impact on health care systems across theglobe in a short period of time. There is a growing body of evidence surroundingthe findings on hybrid imaging with FDG-PET/CT, and this case highlights theimportance of molecular imaging in better understanding of the biomarkers of thedisease which ultimately determine the success in building a model to predict thedisease severity and monitoring the response to treatment.Keywords: COVID-19, 18F-FDG PET/CTIntroductionDecember 2019 saw the first appearance of the 2019 novel coronavirus disease(COVID-19) caused by SARS-CoV-2 in China (Zhu et al. 2020). With the virus rapidlygalloping across the globe, there has been an explosion of publications describing theimaging features of the infection with the bulk of published data focused on character-ising ‘typical’ radiological manifestations of the disease on the respiratory system andpotentially other organs (Zhou et al. 2020; Jajodia et al. 2020). The aim of this case re-port is to illustrate the radiological features of the infection and comment on patternswhich may be used as imaging surrogates of disease activity and severity in vivo basedon 18F-FDG PET/CT (FDG-PET/CT) findings in a critically ill patient infected withCOVID-19 in support of growing literature available on this field (Qin et al. 2020; Zouand Zhu 2020; Kirienko et al. 2020).Case descriptionA 63-year-old Caucasian male with a background of sarcoidosis and factor VIII defi-ciency was admitted to hospital in early March 2020 for workup ahead of commencingimmunosuppressive treatment. CT thorax was performed to assess the known pulmon-ary sarcoidosis and identify any underlying infection ahead of potentially commencingimmunosuppression. The CT at baseline demonstrated no acute pulmonary parenchy-mal abnormality or lymphadenopathy (Fig. 1); however, an incidental 3.4 cm right mid-dle lobe mass was noted (Fig. 2; Image A) and a PET/CT was requested for furthercharacterisation.© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, whichpermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a creditline to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted bystatutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view acopy of this licence, visit http://creativecommons.org/licenses/by/4.0/.European Journal ofHybrid ImagingO’Neill et al. European Journal of Hybrid Imaging            (2020) 4:13 https://doi.org/10.1186/s41824-020-00082-yIn the run up to the PET/CT investigation, the patient became progressively unwellwith the development of a febrile illness and increased oxygen requirement secondary totype I respiratory failure. PET/CT (GE Discovery VCT; USA), performed 9 days followingthe initial CT thorax, demonstrated no FDG uptake in the right middle lobe mass, likely abenign entity (Fig. 2b, c). There were however other unexpected findings which includedintensely FDG positive, predominantly mid- to lower zone, diffuse bilateral subpleuralintra- and interlobular septal thickening and ground-glass opacification, with patchy areasof a higher intensity of FDG uptake in the bases associated with consolidation (Fig. 3a–d).More interestingly, intense FDG uptake was present within an American Thoracic Society(ATS) station level 2R mediastinal lymph node with SUVmax of 8.7 (Fig. 3e–h). Therewas no other FDG-positive abnormality outside the thorax.Due to his increased vulnerability to opportunistic infection secondary to immuno-suppression, and current pandemic of COVID-19 and unbeknown to the PET/CT De-partment staff, the patient had undergone laboratory testing (Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0) for the virus in the time interval between the requesting andperformance of PET/CT and subsequently received a positive diagnosis for COVID-19.Unfortunately, the patient’s clinical condition deteriorated and he passed away 1 weekfollowing PET/CT. One senior member of staff in the PET department, who had comein close contact with the patient required self-isolation for 2 weeks. Consequently, allstaff received training to deal with potential COVID-19 patients including hygiene anddisinfection procedures, handling and moving patients, use of personal protectiveFig. 1 Initial CT thorax demonstrated no acute pulmonary infiltrates or lymphadenopathy (a). Amorphologically normal ATS station 2R lymph node is highlighted by the white arrow (b)Fig. 2 Initial CT thorax detected a right middle lobe mass (a). Subsequent PET-CT demonstrated no FDGuptake b (CT) and c (fused PET-CT)O’Neill et al. European Journal of Hybrid Imaging            (2020) 4:13 Page 2 of 5equipment and restricted contacts in order to maximally reduce the risk oftransmission.DiscussionIn our case, COVID-19 was suspected at the time of interpretation of the PET/CT im-ages, without the knowledge of a positive RT-PCR test, but rather based on the rapiddevelopment of extensive pulmonary infiltrates in a relatively short interval since theunremarkable baseline CT, and the patient’s risk profile. The findings were significantbut certainly unexpected given the clinical question of characterisation of a potentiallung malignancy, which in this case was proven to be a red herring and possibly sec-ondary to an intrapulmonary haematoma related to bleeding diathesis. A number ofkey issues emerge from this case.Firstly, assessment for COVID-19 was not the primary objective and resulted in un-necessary exposure of the staff in the PET/CT department to the virus during thetransfer and preparation of the patient, which ideally should have been postponedpending a negative test result. This case highlights the potential role of nuclear medi-cine departments in the current pandemic in the detection of unexpected COVID-19in patients scanned for other indications. Importantly, as for our case, the majority ofPET/CT studies are performed for oncology patients, often on immunosuppressivetherapy, and therefore requiring urgent medical attention and contact tracing withinoncology units (Albano et al. 2020). It also reinforces the importance of close patientmovement monitoring throughout the hospital during the time interval between testingsuspected cases and laboratory results (Albano et al. 2020; Lu et al. 2020).Next, the imaging findings on the CT component of the study were in line with theother case reports available in the literature and included a crazy-paving pattern withareas of ground-glass infiltration and consolidation in a subpleural distribution (Zuet al. 2020). Furthermore, the extent and intensity of FDG uptake in the lungs, con-cordant with the areas of CT abnormality, were thought to be indicative of activeFig. 3 a PET maximum intensity projection (MIP), b–d: axial attenuation corrected PET, axial CT lungwindows and axial fused PET/CT images through the lower thorax. e PET maximum intensity projection(MIP), f–h: axial attenuation corrected PET, axial CT mediastinal windows and axial fused PET/CT imagesthrough the superior mediastinum. These images highlight intense bilateral parenchymal metabolic activity,more prominently in the right lower lobe (images a–d) and high uptake in an ATS station 2R lymph node(e–h). Please note spurious right ureteric activity on the MIP images (images a and e)O’Neill et al. European Journal of Hybrid Imaging            (2020) 4:13 Page 3 of 5COVID-19 infection (Zu et al. 2020). Having since imaged a number of other con-firmed or suspected cases with less pronounced FDG activity on PET/CT, and particu-larly since “casual FDG uptake” has been shown to be a feature of COVID-19 infectionin a small case series of asymptomatic patients in a recent publication, the possibility ofa more aggressive strain of the virus, and patient’s immunosuppression may have beenthe contributing factors (Setti et al. 2020). Based on our findings and limited availableevidence from other investigators, there may be a role in the future for PET/CT in themanagement of patients during the endemic phase to assist in the differential diagnosis,differentiating active from non-active disease and assessment of the response to treat-ment (Deng et al. 2020). Critically, the location of the intensely FDG-positive normalsize upper mediastinal lymph node, demonstrated in our case study, was discordantwith the distribution of the pulmonary parenchymal involvement. This may suggestthat lymphadenopathy could be an independent imaging biomarker of the disease, simi-lar to what demonstrated for other infections (Chadburn et al. 1989). Indeed, based onlimited data, lymphadenopathy has been suggested as a prognostic marker of COVID-19 infection severity (Valette et al. 2020) and a predictor of a worse outcome (Sardanelliet al. 2020). In view of the grave clinical outcome of our patient, there may be an argu-ment in support of a further prognostic role of higher SUVmax values of FDG positivenodal disease, as a biomarker which could herald a more severe case of the infectionwith the virus.Finally, the presence of nodal uptake, in a more suggestive setting of malignancy suchas lymphoma or lung tumour, could have erroneously resulted in over-staging of thenodal disease (Zanoni et al. n.d.).ConclusionCT is the primary cross-sectional diagnostic imaging modality of choice in the assess-ment of severe cases when clinically indicated. This case study however highlights theimportance of the metabolic activity provoked in the lung parenchyma by COVID-19infection which could be illustrated only with PET/CT. It also underlines the potentialvalue of PET/CT and molecular imaging in the future, in determining disease activityand severity based on some of the recent observations and limited available data. How-ever, until a clear role for PET/CT in COVID-19 is established through further re-search, unnecessary potential exposures to staff and other patients should be avoidedby careful screening of the patients for COVID-19 infection in suspected cases prior toPET/CT for malignancy workup, particularly when the primary is in the thorax to avoidpitfalls.Code availabilityNot applicable.Authors’ contributionsHO participated in writing the manuscript and referencing. SD participated in selecting the images and preparingthem to the standards of the journal. FF participated in editing the text and expanding the discussion. ANcorresponding author, developing ideas, extensive involvement in preparing the manuscript, checking and updatingthe text and references, overhaul managment of the process. The author(s) read and approved the final manuscript.FundingNo funding was received for this study.Availability of data and materialsNot applicable.O’Neill et al. European Journal of Hybrid Imaging            (2020) 4:13 Page 4 of 5Ethics approval and consent to participateNot applicable.Consent for publicationThe requirement to obtain informed consent was waived according to institutional guidelines.Competing interestsThe authors declare that they have no competing interests.Author details1Department of Radiology, St. James’s Hospital, D08 X4RX Dublin, Ireland. 2University College London Hospitals (UCLH),5th Floor UCH, 235 Euston Rd, London NW1 2BU, UK.Received: 8 June 2020 Accepted: 10 July 2020ReferencesAlbano D, Bertagna F, Bertoli M, Bosio G, Lucchini S, Motta F, Panarotto MB, Peli A, Camoni L, Bengel FM, Giubbini R (2020May) Incidental findings suggestive of COVID-19 in asymptomatic patients undergoing nuclear medicine procedures in ahigh-prevalence region. 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A twisted tale-radiological imaging features of COVID-19 on ¹⁸F-FDG PET/CT

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A twisted tale-radiological imaging features of COVID-19 on ¹⁸F-FDG PET/CT

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