Journal Pre-proof Magnetic resonance imaging features of coronavirus disease 2019 (COVID-19) pneumonia: The first preliminary case series Pooya Torkian, Hamid Rajebi, Naghi Ramezani, Pejman Kiani, Shahram Akhlaghpoor PII: S0899-7071(20)30344-2 DOI: https://doi.org/10.1016/j.clinimag.2020.09.002 Reference: JCT 9063 To appear in: Clinical Imaging Received date: 27 May 2020 Revised date: 4 August 2020 Accepted date: 11 September 2020 Please cite this article as: P. Torkian, H. Rajebi, N. Ramezani, et al., Magnetic resonance imaging features of coronavirus disease 2019 (COVID-19) pneumonia: The first preliminary case series, Clinical Imaging (2020), https://doi.org/10.1016/ j.clinimag.2020.09.002 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier. Journal Pre-proof Magnetic Resonance Imaging Features of Coronavirus Disease 2019 (COVID-19) Pneumonia: The First Preliminary Case Series Authors of Pooya Torkian¹, MD; Hamid Rajebi², MD; Naghi Ramezani3, MD; Pejman Kiani3, PhD ; ro Shahram Akhlaghpoorᶾ, MD 1. Shahid Beheshti University of Medical Sciences, Tehran, Iran -p 2. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, re Boston, MA, USA Corresponding Author na Shahram Akhlaghpoor, MD. lP 3. Pardis Noor Medical Imaging Center, Tehran, Iran Tehran, Iran. Jo ur Address: Pardis Noor Medical Imaging Center, No 5, 25th street, Sa’adat abad street, Phone: +098-912-1096762 / +98-21-22258248 Email: Shahram_ak@yahoo.com / akhlaghpoor@pardisnoor.com / Rationale and Objectives There is a rising onus on understanding the common features of COVID-19 pneumonia on different imaging modalities. In this study, we aimed to review and depict the common MRI features of COVID-19 pneumonia in our laboratory confirmed case series, the first comprehensive reported cohort in the literature. Materials and Methods Journal Pre-proof Upon IRB approval, eight laboratory confirmed COVID-19 patients who presented to our outpatient imaging clinic underwent chest CT and, once various features of COVID-19 pneumonia were identified, a dedicated multisequence chest MRI was performed on the same day with an institutional protocol. Demographic data and the morphology, laterality and location of the lesions were recorded for each case. Results Five males and three females with the mean age of 40.63 ± 12.64 years old were present of in this case series. Five case had typical CT features with ground glass opacities and consolidations, readily visible on different MRI sequences. Three cases had indeterminate ro or atypical features which were also easily seen on MRI. The comprehensive review of -p MRI features for each case and representative images have been illustrated. re Conclusion lP Becoming familiar with typical findings of COVID-19 pneumonia in MRI is crucial for every radiologist. Although MRI is not the modality of choice for evaluation of pulmonary opacities, it has similar capabilities in detection of COVID-19 pneumonia na when compared to chest CT. Jo ur Keywords: COVID-19 Pneumonia; Coronavirus; Magnetic Resonance Imaging Introduction The outbreak of highly infectious novel coronavirus, known as coronavirus disease 2019 (COVID-19), has caused an emerging global health threat with more than 2,800,000 confirmed cased worldwide based on world health organization daily report as of April 26th, 2020 (1). With continued surge in COVID-19 cases, the number of imaging studies in persons under investigation or confirmed positive patients (both for COVID-19 related or unrelated reasons) are increasing overtime. This has placed a rising onus on understanding the common features of COVID-19 pneumonia on different imaging Journal Pre-proof modalities. Although not routinely recommended, chest computed tomography (CT) is still the cornerstone of the radiologic evaluation which aids in the detection of equivocal cases, follow-up of clinically deteriorating confirmed cases, predicting mortality and early detection of complications (2-5). Cross-sectional imaging is recommended for patients with higher risk for complication, those with comorbidities, not responding to supportive of treatment and presenting with acute clinical deterioration, per WHO rapid advice guide ro (6). Chest CT imaging features of COVID-19 has been well described in the literature. A -p few recent studies have demonstrated radiologic features of COVID-19 pneumonia in re other diagnostic modalities, like ultrasound and PET-CT (7, 8) but no dedicated report lP has described magnetic resonance imaging (MRI) features of the disease. Assessing the presence of common features of COVID-19 pneumonia as an incidental na finding in MRIs performed for other reasons such as thoracic, abdomen or cardiac MRIs Jo ur is necessary for every radiologist. Despite the widespread utilization of chest CT, there is an existing debate on radiation burden for the patients who undergo multiple CTs in a short time interval for follow-up purposes, especially in pediatric age group or when they are pregnant (9). Thus, this case series may start a preliminary platform for the role of MRI in disease follow-up after resolution of the symptoms, although future more comprehensive studies are required. In this pilot study, we aimed to review and depict the common MRI features of COVID19 pneumonia in our laboratory confirmed case series, the first comprehensive reported cohort in the literature. Journal Pre-proof Materials and methods Upon IRB approval, written informed consents were obtained from eight laboratory confirmed (positive RT-PCR test, three to six days before imaging) COVID-19 patients who presented to our outpatient imaging clinic in Rasht, Iran between March 20 and April 8, 2020. All included patients had mild symptoms during the acute phase of the of disease and did not need supplementary oxygen therapy. They first underwent chest CT (1-mm slice thickness with a 16-slices SOMATOM Scope CT scanner, Siemens, ro Germany) and once typical, indeterminate or atypical features of COVID-19 pneumonia -p (9) were identified, a dedicated chest MRI (1.5 T MR system, Magnetom Avanto, re Siemens, Erlangen, Germany) was performed on the same day. lP Our MRI protocols included; 1- Coronal T2-half Fourier single-shot turbo spin-echo (HASTE), 2-Axial T2-HASTE, 3-Sagittal T2 HASTE, 4-Axial T1 3D-gradient echo na volumetric interpolated breath-hold examination (VIBE), and 5-Coronal true fast imaging Jo ur with steady state precession (FISP), obtained using the breath holding technique, as well as, 6-Coronal T2- turbo spin echo (TSE)-turbo inversion recovery magnitude (TIRM), 7Axial T2-TSE-TIRM, and 8-Axial diffusion-weighted imaging (DWI) (with b-values equal to 0 s/mm2, 400 s/mm2, and 800 s/mm2), obtained using respiratory gating. All the protocols were implemented for each patient under a total cycle time of 12-15 minutes. Both MRI and CT images were reviewed by a radiologist with 10-year experience and the morphology, laterality and location of the lesions were recorded for each case. The chest CT features were categorized as typical, indeterminate and atypical based on Radiological Society of North America (RSNA) expert consensus statement (10). Journal Pre-proof Results Five males and three females with the mean age of 40.63 ± 12.64 years old were present in this case series. A comprehensive review of MRI features for each case have been presented in table 1. We also reported type of CT manifestation based on the recent RSNA expert consensus statement. Several representative MR images with distinguishing features are exemplified in the following five cases (Figures 1-5). The remaining three of cases had similar radiologic pattern to one or more of the below mentioned cases. ro Although these features are not specific for COVID-19 pneumonia, given the clinical -p presentation, confirmed laboratory RT-PCR, and ongoing pandemic, finding are highly re suggestive of COVID-19 pneumonia. lP CASE 1: Ground Glass Opacities (GGO) and Reverse Halo Sign (Figure 1a and 1b) na CASE 2: Consolidation (Figure 2) CASE 3: Consolidation + Reticulation (Figure 3) Jo ur CASE 4a: Dominant reticular pattern with improving pneumonia (Figure 4a) CASE 4b: GGO pattern with resolving pneumonia (Figure 4b) CASE 5: Consolidation in DWI sequence (Figure 5) Discussion Although American College of Radiology statement recommends minimizing MRI utilization in COVID-19 pandemic (11), urgent cases are still performed, and elective MRIs will show increasing trend in upcoming days. Lung parenchyma is at least partially visible on different protocols of cardiac, thoracic spine and abdomen MRIs. Given the Journal Pre-proof high prevalence and contagiousness of the COVID-19 infection, radiologists are going to encounter the many features of the associated pneumonia in their daily practice even when the MR studies are performed for other reasons. Furthermore, the reported cardiac involvement in COVID-19 infection will occasionally necessitate acquiring cardiac MR (12). There is also open debate over associated radiation burden with CTs performed in at-risk groups like pediatric patients and pregnant females, hence raising the potential for of performing state-of-the-art chest MR as a radiation-free modality in diagnosing COVID- ro 19 pneumonia in such groups, although the challenges related to disinfection of the -p equipment still exists. Finally, though not well studied yet, it appears that clinically re recovered COVID-19 patients may have cardiopulmonary sequelae later which may need dedicated radiologic surveillance. In that case, chest MRI examination is a viable na imaging. lP alternative in the aforementioned groups and those who may need frequent follow up Jo ur To our knowledge, this is the first case series evaluating COVID-19 pneumonia on chest MRI. Our preliminary data on eight COVID-19 positive patients, showed that common CT manifestation of COVID-19 pneumonia such as bilateral multifocal ground-glass, consolidative, nodular or reticular opacities can be identified and distinguished on MRI, although the imaging features are not specific. It has been shown that lung MRI is as efficient and accurate as chest CT imaging in providing fine details of the lung parenchyma and pleural abnormalities in patients with lower respiratory tract infection (13), but the actual practical role is limited by loss of signal due to physiologic respiratory and cardiac motion, and low amount of hydrogen protons in the lung parenchyma (14). Advancement in applicable sequence Journal Pre-proof techniques has enabled to compensate for these defects by providing different aspects of lung pathology. As part of the inflammatory process, any increase in lung proton density due to solid lesions or infiltration with fluids corresponds to areas of increased signal intensity, which can be easily detected with MRI (15). T2-weighted sequences such as HASTE, TSE, FISP and TIRM are widely accepted to increase the detection accuracy of lung infiltration (16). Hence, various radiologic manifestation of COVID-19 pneumonia of such as GGO, consolidations and ill-defined reticulations can be easily distinguished with ro lung MRI. -p Among various MRI sequences, the T2W TSE-TIRM sequence shows lesions more re brightly compared to other sequences. The increased signal intensity of the lesion in the lP T2W TSE-TIRM sequence is mostly due to edema, which is expected to be more observed in the inflammatory process of COVID-19 pneumonia. Also, our limited cases na suggested that lung MRI could determine the different infiltration stages of the lung Jo ur parenchyma. Dedicated statistically higher-level studies should be performed to determine the importance of each sequence in evaluation of COVID-19 pneumonia. Overall, our study drives home the fact that chest MRI can act as a potential alternative to chest CT in follow-up of COVID-19 pneumonia although further studies are warranted. This also holds true in patients who require chest MRI for other indications such as vascular emergencies, myocardial infarction, or myocarditis, or routine MR spine and MR-PET for cancer staging. It is worth mentioning that a major limitation to MRI utilization in COVID-19 era is the potential risks associated with infection control after using the imaging equipment. Another limitation to our study is that our case series consisted of relatively young patients. Thus, larger and more diverse studies including Journal Pre-proof different spectrum of ages are warranted to elucidate more details about the lung MRI findings of COVID-19 and to reliably examine the diagnostic accuracy, sensitivity, specificity, false negative rate, and cost-effectiveness of lung MRI compared to the CT in diagnosis of COVID-19 pneumonia. There is no doubt that development and adoption of a standardized MRI protocol is required prior to clinical implementation of this technique. ro of Conclusion -p Becoming familiar with typical findings of COVID-19 pneumonia in MRI is crucial for every radiologist. Although MRI is not the modality of choice for evaluation of re pulmonary opacities, it has similar capabilities in detection of COVID-19 pneumonia na Conflict of interest lP when compared to chest CT. The authors declare no conflict of interest. This research did not receive any specific Jo ur grant from funding agencies in the public, commercial, or not-for-profit sectors. Protocol of the study and data will be available upon request. References 1. Word Health Organization. Novel Coronavirus (COVID-19) situation. https://covid19.who.int. Accessed 26 April 2020. 2. Leonard-Lorant I, Delabranche X, Severac F, et al. Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to DDimer Levels. Radiology 2020. https://doi.org/10.1148/radiol.2020201561 3. Colombi D, Bodini FC, Petrini M, at al. Well-aerated Lung on Admitting Chest Journal Pre-proof CT to Predict Adverse Outcome in COVID-19 Pneumonia. Radiology 2020. https://doi.org/10.1148/radiol.2020201433 4. Yang R, Li X, Liu H, et al. Chest CT Severity Score: An Imaging Tool for Assessing Severe COVID-19. Radiology: Cardiothoracic Imaging 2020. https://doi.org/10.1148/ryct.2020200047 5. Tabatabaei SMH, Talari H, Moghaddas F, et al. Computed Tomographic A Single-Center Study from Kashan, ro Pneumonia: of Features and Short-term Prognosis of Coronavirus Disease 2019 (COVID-19) Iran. Radiology: -p Cardiothoracic Imaging, 2020. https://doi.org/10.1148/ryct.2020200130 re 6. Elie A. Akl, Ivana Blazic, Sally Yaacoub, et al. Use of Chest Imaging in the lP Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide. Radiology (2020). DOI: https://doi.org/10.1148/radiol.2020203173 na 7. Qin C, Liu F, Yen T, et al. 18F-FDG PET/CT findings of COVID-19: a series of Jo ur four highly suspected cases. European Journal of Nuclear Medicine and Molecular Imaging 47, 1281–1286(2020). https://doi.org/10.1007/s00259020-04734-w 8. Buonsenso D, Piano A, Raffaelli F, et al. Point-of-Care Lung Ultrasound findings in novel coronavirus disease-19 pnemoniae: a case report and potential applications during COVID-19 outbreak. European Review for Medical and Pharmacological Sciences. 2020 Mar;24(5):2776-2780. https://doi:10.26355/eurrev_202003_20549. 9. Rehani MM, Yang K, Melick ER, et al. Patients undergoing recurrent CT scans: assessing the magnitude. European Radiology. 2020 Apr;30(4):1828-1836. Journal Pre-proof https://doi.org/10.1007/s00330-019-06523-y 10. Simpson S, Kay F, Abbara S, et al. Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA. Radiology: Cardiothoracic Imaging 2020. https://doi.org/10.1148/ryct.2020200152 of 11. ACR Guidance on COVID-19 and MR Use.https://www.acr.org/Clinical- ro Resources/Radiology-Safety/MR-Safety/COVID-19-and-MR-Use. -p April 24, 2020. Accessed re 12. Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With lP Coronavirus Disease 2019 (COVID-19). JAMA Cardiology 2020 Mar 27. https://doi.org/10.1001/jamacardio.2020.1096. na 13. Syrjala H, Broas M, Ohtonen P, et al. Chest magnetic resonance imaging for Jo ur pneumonia diagnosis in outpatients with lower respiratory tract infection. European Respiratory Journal. 2017;49(1):1601303. https://doi.org/10.1183/13993003.01303-2016. 14. Leutner CC, Gieseke J, Lutterbey G, et al. MR imaging of pneumonia in immunocompromised patients: comparison with helical CT. American Journal of Roentgenology 2000 Aug;175(2):391-7. https://doi.org/10.2214/ajr.175.2.1750391 15. Wielpütz M, Kauczor H-U. MRI of the lung: state of the art. Diagnostic and interventional radiology. 2012;18(4):344. https://doi.org/10.4261/13053825.DIR.5365-11.0 Journal Pre-proof Jo ur na lP re -p ro of 16. Kauczor H-U, Wielpütz MO. MRI of the Lung: Springer; 2018. Journal Pre-proof Figure legends: Fig 1a. 36-year-old female with confirmed COVID-19, seven days from her symptom onset. (A) Axial CT image demonstrating ground glass opacity (GGO) in the right lower lobe. (B) T2W True-FISP sequence demonstrating hyperintense opacity in the right lower lobe of the lung (arrow) corresponding to chest CT finding. (C) T1W VIBE sequence revealed intermediate to hypointense signal at the same region. (D) T2W TSE-TIRM sequence demonstrating heterogeneous high signal intensity within the known GGO, due of to its different components admixed with minimal pleural thickening/effusion, the later not clearly visible in CT. ro Fig 1b. In same patient, (A) Axial CT images demonstrating “reverse halo” sign. -p (B) Axial True-FISP sequence of MRI demonstrating central areas of GGO attenuation re with surrounding consolidation, also representing “reverse halo”. lP Fig 2. A 31-year-old male patient with confirmed COVID-19, presenting after three days of his symptom onset. (A) Axial CT image demonstrating areas of peripheral na consolidative and nodular opacities in bilateral lower lobes. (B) T2W HASTE sequence showing multiple peripheral located consolidations in both lobes that are hyperintense to Jo ur skeletal muscle. (C) T1W VIBE sequence demonstrating isointense areas when compared skeletal muscle. This finding was different from hypointensity of GGO in case 1. (D) T2W TSE-TIRM sequence demonstrating similar findings to T2W HASTE sequence, slightly brighter. Fig 3. Axial images of 35-year-old male patient with COVID-19 six days from his symptom onset. (A) Axial CT image demonstrating peripheral consolidation in the right lower lobe of the lung, accompanied by pleural-based reticulation in both lower lobes. (B) T2W TSE-TIRM sequence demonstrating consolidation in the right lower lobe of the lung which shows heterogeneous high-signal-intensity lesion. (C) T2W True-FISP and (D) T2W HASTE sequence have shown a more precise delineation of reticular opacities. Journal Pre-proof Fig 4a. 56-year-old male patient two weeks after receiving treatment with clinical improvement. (A) CT image demonstrating a reticular pattern with partially resolving GGO indicating resolution stage of pneumonia. (B) Axial T2W TSE-TIRM sequence showing peripheral areas of increased signal intensity with pleural thickening and scattered intensities; however, reticulation is not well seen on this sequence. (C) T1W VIBE sequence showing decreased signal intensity of the signal in the area when compared to skeletal muscle. (D)Axial T2W HASTE sequence demonstrating better anatomic correlation with CT image, with partial visualization of reticulation in this of sequence. ro Fig 4b. Same patient 56-year-old male presenting two weeks from symptom onset. (A) CT chest demonstrating hazy improving GGO. (B) T2W TSE –TIRM sequence -p demonstrating multiple GGOs in both lobes of his lung that is more pronounced re compared to CT image. However, (C) T1W VIBE sequence signal intensity is markedly decreased in contrast to skeletal muscle and are not readily visible. In (D) T2W HASTE na lP sequence, the signal intensity is also reduced. Fig 5. 34-year-old female patient with confirmed COVID-19 presenting seven days after Jo ur her symptom onset. (A) Axial CT image demonstrating peripheral area of consolidation in the right lower lobe. DW-MRI sequence obtained by respiratory gating (B) b-value =400 and (C) b-value =800, which shows a signal drop by increasing the b-value. This finding indicates the mixed component of free fluid, increased cell population and edema within the lesion. (D) ADC map, the white area in this sequence indicates the free fluid component. Journal Pre-proof Table 1. Demographic data with morphology, laterality and location of the MRI features of COVID-19 pneumonia in our case series. Presence or absence of pleural effusion/thickening and CT classification of the disease were also mentioned. Case Age/ GGO Consolidation Reticular Reverse opacities halo Laterality Involved lobes Peripheral disease Pleural CT chest effusion/thickening features gender 34/M No No Yes No Unilateral Yes RUL, RLL No Indeterminate 2 35/M No Yes Yes No Bilateral Yes All lobes No, +thickening Typical 3 36/F Yes Yes No Yes Unilateral Yes RLL No Typical 4 57/F No Yes No No Bilateral Yes RUL, RLL, LUL, No Indeterminate LLL 30/M Yes Yes Yes No Bilateral Yes RLL, LLL No, +thickening Typical 6 23/F No Yes Yes No Bilateral No RML, RLL, LUL, Yes Atypical No Typical No Typical 56/M Yes No No lP Yes Yes No Yes na 8 38/F No Jo ur 7 re 5 -p ro of 1 Bilateral Bilateral LLL Yes RUL, RLL, LUL, LLL No All lobes F: female, M: male, GGO: ground glass opacity, RUL: right upper lobe, RML: right middle lobe, RLL: right lower lobe, LUL: left upper lobe, LLL: left lower lobe Journal Pre-proof Highlights: MRI utilization in targeted at-risk groups of patients and healthcare workers in the era of COVID-19 pandemic Becoming familiar with typical findings of COVID-19 pneumonia in MRI Chest MRI can act as a potential alternative to chest CT in follow-up of COVID-19 Jo ur na lP re -p ro of pneumonia when ionizing radiation exposure is a consideration Figure 1 Figure 2 Figure 3 Figure 4 Figure 5