AI support for accurate and fast radiological diagnosis of COVID-19: an international multicenter, multivendor CT study.

OBJECTIVES: Differentiation between COVID-19 and community-acquired pneumonia (CAP) in computed tomography (CT) is a task that can be performed by human radiologists and artificial intelligence (AI). The present study aims to (1) develop an AI algorithm for differentiating COVID-19 from CAP and (2) evaluate its performance. (3) Evaluate the benefit of using the AI result as assistance for radiological diagnosis and the impact on relevant parameters such as accuracy of the diagnosis, diagnostic time, and confidence. METHODS: We included n = 1591 multicenter, multivendor chest CT scans and divided them into AI training and validation datasets to develop an AI algorithm (n = 991 CT scans; n = 462 COVID-19, and n = 529 CAP) from three centers in China. An independent Chinese and German test dataset of n = 600 CT scans from six centers (COVID-19 / CAP; n = 300 each) was used to test the performance of eight blinded radiologists and the AI algorithm. A subtest dataset (180 CT scans; n = 90 each) was used to evaluate the radiologists' performance without and with AI assistance to quantify changes in diagnostic accuracy, reporting time, and diagnostic confidence. RESULTS: The diagnostic accuracy of the AI algorithm in the Chinese-German test dataset was 76.5%. Without AI assistance, the eight radiologists' diagnostic accuracy was 79.1% and increased with AI assistance to 81.5%, going along with significantly shorter decision times and higher confidence scores. CONCLUSION: This large multicenter study demonstrates that AI assistance in CT-based differentiation of COVID-19 and CAP increases radiological performance with higher accuracy and specificity, faster diagnostic time, and improved diagnostic confidence. KEY POINTS: • AI can help radiologists to get higher diagnostic accuracy, make faster decisions, and improve diagnostic confidence. • The China-German multicenter study demonstrates the advantages of a human-machine interaction using AI in clinical radiology for diagnostic differentiation between COVID-19 and CAP in CT scans.

Morphological appearance of the B.1.1.7 mutation of the novel coronavirus 2 (SARS-CoV-2) in chest CT.

Background: Diagnosing a coronavirus disease 2019 (COVID-19) infection with high specificity in chest computed tomography (CT) imaging is considered possible due to distinctive imaging features of COVID-19 pneumonia. Since other viral non-COVID pneumonia show mostly a different distribution pattern, it is reasonable to assume that the patterns observed caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a consequence of its genetically encoded molecular properties when interacting with the respiratory tissue. As more mutations of the initial SARS-CoV-2 wild-type with varying aggressiveness have been detected in the course of 2021, it became obvious that its genome is in a state of transformation and therefore a potential modification of the specific morphological appearance in CT may occur. The aim of this study was to quantitatively analyze the morphological differences of the SARS-CoV-2-B.1.1.7 mutation and wildtype variant in CT scans of the thorax. Methods: We analyzed a dataset of 140 patients, which was divided into pneumonias caused by n=40 wildtype variants, n=40 B.1.1.7 variants, n=20 bacterial pneumonias, n=20 viral (non-COVID) pneumonias, and a test group of n=20 unremarkable CT examinations of the thorax. Semiautomated 3D segmentation of the lung tissue was performed for quantification of lung pathologies. The extent, ratio, and specific distribution of inflammatory affected lung tissue in each group were compared in a multivariate group analysis. Results: Lung segmentation revealed significant difference between the extent of ground glass opacities (GGO) or consolidation comparing SARS-CoV-2 wild-type and B.1.1.7 variant. Wildtype and B.1.1.7 variant showed both a symmetric distribution pattern of stage-dependent GGO and consolidation within matched COVID-19 stages. Viral non-COVID pneumonias had significantly fewer consolidations than the bacterial, but also than the COVID-19 B.1.1.7 variant groups. Conclusions: CT based segmentation showed no significant difference between the morphological appearance of the COVID-19 wild-type variant and the SARS-CoV-2 B.1.1.7 mutation. However, our approach allowed a semiautomatic quantification of bacterial and viral lung pathologies. Quantitative CT image analyses, such as the one presented, appear to be an important component of pandemic preparedness considering an organism with ongoing genetic change, to describe a potential arising change in CT morphological appearance of possible new upcoming COVID-19 variants of concern.

Assessment of COVID-19 lung involvement on computed tomography by deep-learning-, threshold-, and human reader-based approaches-an international, multi-center comparative study.

Background: The extent of lung involvement in coronavirus disease 2019 (COVID-19) pneumonia, quantified on computed tomography (CT), is an established biomarker for prognosis and guides clinical decision-making. The clinical standard is semi-quantitative scoring of lung involvement by an experienced reader. We aim to compare the performance of automated deep-learning- and threshold-based methods to the manual semi-quantitative lung scoring. Further, we aim to investigate an optimal threshold for quantification of involved lung in COVID pneumonia chest CT, using a multi-center dataset. Methods: In total 250 patients were included, 50 consecutive patients with RT-PCR confirmed COVID-19 from our local institutional database, and another 200 patients from four international datasets (n=50 each). Lung involvement was scored semi-quantitatively by three experienced radiologists according to the established chest CT score (CCS) ranging from 0-25. Inter-rater reliability was reported by the intraclass correlation coefficient (ICC). Deep-learning-based segmentation of ground-glass and consolidation was obtained by CT Pulmo Auto Results prototype plugin on IntelliSpace Discovery (Philips Healthcare, The Netherlands). Threshold-based segmentation of involved lung was implemented using an open-source tool for whole-lung segmentation under the presence of severe pathologies (R231CovidWeb, Hofmanninger et al., 2020) and consecutive quantitative assessment of lung attenuation. The best threshold was investigated by training and testing a linear regression of deep-learning and threshold-based results in a five-fold cross validation strategy. Results: Median CCS among 250 evaluated patients was 10 [6-15]. Inter-rater reliability of the CCS was excellent [ICC 0.97 (0.97-0.98)]. Best attenuation threshold for identification of involved lung was -522 HU. While the relationship of deep-learning- and threshold-based quantification was linear and strong (r2 deep-learning vs. threshold=0.84), both automated quantification methods translated to the semi-quantitative CCS in a non-linear fashion, with an increasing slope towards higher CCS (r2 deep-learning vs. CCS= 0.80, r2 threshold vs. CCS=0.63). Conclusions: The manual semi-quantitative CCS underestimates the extent of COVID pneumonia in higher score ranges, which limits its clinical usefulness in cases of severe disease. Clinical implementation of fully automated methods, such as deep-learning or threshold-based approaches (best threshold in our multi-center dataset: -522 HU), might save time of trained personnel, abolish inter-reader variability, and allow for truly quantitative, linear assessment of COVID lung involvement.

Meaningful use of imaging resources to rule out cerebral venous sinus thrombosis after ChAdOx1 COVID-19 vaccination: Evaluation of the AHA diagnostic algorithm with a clinical cohort and a systematic data review.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) with cerebral venous thrombosis (CVST) is an improbable (0.0005%), however potentially lethal complication after ChAdOx1 vaccination. On the other hand, headache is among the most frequent side effects of ChAdOx1 (29.3%). In September 2021, the American Heart Association (AHA) suggested a diagnostic workflow to facilitate risk-adapted use of imaging resources for patients with neurological symptoms after ChAdOx1. We aimed to evaluate the AHA workflow in a retrospective patient cohort presenting at four primary care hospitals in Germany for neurological complaints after ChAdOx1. Scientific literature was screened for case reports of VITT with CVST after ChAdOx1, published until September 1st, 2021. One-hundred-thirteen consecutive patients (77 female, mean age 38.7 +/- 11.9 years) were evaluated at our institutes, including one case of VITT with CVST. Further 228 case reports of VITT with CVST are published in recent literature, which share thrombocytopenia (225/227 reported) and elevated d-dimer levels (100/101 reported). The AHA workflow would have recognized all VITT cases with CVST (100% sensitivity), the number needed to diagnose (NND) was 1:113. Initial evaluation of thrombocytopenia or elevated d-dimer levels would have lowered the NND to 1:68, without cost of sensitivity. Hence, we suggest that in case of normal thrombocyte and d-dimer levels, the access to further diagnostics should be limited by the established clinical considerations regardless of vaccination history.

Quantitative determination of pulmonary emphysema in follow-up LD-CTs of patients with COVID-19 infection.

PURPOSE: To evaluate the association between the coronavirus disease 2019 (COVID-19) and post-inflammatory emphysematous lung alterations on follow-up low-dose CT scans. METHODS: Consecutive patients with proven COVID-19 infection and a follow-up CT were retrospectively reviewed. The severity of pulmonary involvement was classified as mild, moderate and severe. Total lung volume, emphysema volume and the ratio of emphysema/-to-lung volume were quantified semi-automatically and compared inter-individually between initial and follow-up CT and to a control group of healthy, age- and sex-matched patients. Lung density was further assessed by drawing circular regions of interest (ROIs) into non-affected regions of the upper lobes. RESULTS: A total of 32 individuals (mean age: 64 ± 13 years, 12 females) with at least one follow-up CT (mean: 52 ± 66 days, range: 5-259) were included. In the overall cohort, total lung volume, emphysema volume and the ratio of lung-to-emphysema volume did not differ significantly between the initial and follow-up scans. In the subgroup of COVID-19 patients with > 30 days of follow-up, the emphysema volume was significantly larger as compared to the subgroup with a follow-up < 30 days (p = 0.045). Manually measured single ROIs generally yielded lower attenuation values prior to COVID-19 pneumonia, but the difference was not significant between groups (all p > 0.05). CONCLUSION: COVID-19 patients with a follow-up CT >30 days showed significant emphysematous lung alterations. These findings may help to explain the long-term effect of COVID-19 on pulmonary function and warrant validation by further studies.

Coronary artery calcification on low-dose chest CT is an early predictor of severe progression of COVID-19-A multi-center, multi-vendor study.

PURPOSE: Cardiovascular comorbidity anticipates severe progression of COVID-19 and becomes evident by coronary artery calcification (CAC) on low-dose chest computed tomography (LDCT). The purpose of this study was to predict a patient's obligation of intensive care treatment by evaluating the coronary calcium burden on the initial diagnostic LDCT. METHODS: Eighty-nine consecutive patients with parallel LDCT and positive RT-PCR for SARS-CoV-2 were included from three centers. The primary endpoint was admission to ICU, tracheal intubation, or death in the 22-day follow-up period. CAC burden was represented by the Agatston score. Multivariate logistic regression was modeled for prediction of the primary endpoint by the independent variables "Agatston score > 0", as well as the CT lung involvement score, patient sex, age, clinical predictors of severe COVID-19 progression (history of hypertension, diabetes, prior cardiovascular event, active smoking, or hyperlipidemia), and laboratory parameters (creatinine, C-reactive protein, leucocyte, as well as thrombocyte counts, relative lymphocyte count, d-dimer, and lactate dehydrogenase levels). RESULTS: After excluding multicollinearity, "Agatston score >0" was an independent regressor within multivariate analysis for prediction of the primary endpoint (p<0.01). Further independent regressors were creatinine (p = 0.02) and leucocyte count (p = 0.04). The Agatston score was significantly higher for COVID-19 cases which completed the primary endpoint (64.2 [interquartile range 1.7-409.4] vs. 0 [interquartile range 0-0]). CONCLUSION: CAC scoring on LDCT might help to predict future obligation of intensive care treatment at the day of patient admission to the hospital.

Calcification of the thoracic aorta on low-dose chest CT predicts severe COVID-19.

BACKGROUND: Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. METHODS: Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor's software. RESULTS: Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only. CONCLUSION: AWC seems to be an independent biomarker for the prediction of severe progression and intensive care treatment of COVID-19 already at the time of patient admission to the hospital; verification in a larger multi-center, multi-vendor study is desired.

Early extrapulmonary prognostic features in chest computed tomography in COVID-19 pneumonia: Bone mineral density is a relevant predictor for the clinical outcome - A multicenter feasibility study.

BACKGROUND: Besides throat-nose swab polymerase chain reaction (PCR), unenhanced chest computed tomography (CT) is a recommended diagnostic tool for early detection and quantification of pulmonary changes in COVID-19 pneumonia caused by the novel corona virus. Demographic factors, especially age and comorbidities, are major determinants of the outcome in COVID-19 infection. This study examines the extra pulmonary parameter of bone mineral density (BMD) from an initial chest computed tomography as an associated variable of pre-existing comorbidities like chronic lung disease or demographic factors to determine the later patient's outcome, in particular whether treatment on an intensive care unit (ICU) was necessary in infected patients. METHODS: We analyzed 58 PCR-confirmed COVID-19 infections that received an unenhanced CT at admission at one of the included centers. In addition to the extent of pulmonary involvement, we performed a phantomless assessment of bone mineral density of thoracic vertebra 9-12. RESULTS: In a univariate regression analysis BMD was found to be a significant predictor of the necessity for intensive care unit treatment of COVID-19 patients. In the subgroup requiring intensive care treatment within the follow-up period a significantly lower BMD was found. In a multivariate logistic regression model considering gender, age and CT measurements of bone mineral density, BMD was eliminated from the regression analysis as a significant predictor. CONCLUSION: Phantomless assessed BMD provides prognostic information on the necessity for ICU treatment in course of COVID-19 pneumonia. We recommend using the measurement of BMD in an initial CT image to facilitate a potentially better prediction of severe patient outcomes within the 22 days after an initial CT scan. Consequently, in the present sample, additional bone density analysis did not result in a prognostic advantage over simply considering age. Significantly larger patient cohorts with a more homogenous patient age should be performed in the future to illustrate potential effects. CLINICAL RELEVANCE: While clinical capacities such as ICU beds and ventilators are more crucial than ever to help manage the current global corona pandemic, this work introduces an approach that can be used in a cost-effective way to help determine the amount of these rare clinical resources required in the near future.

Body composition on low dose chest CT is a significant predictor of poor clinical outcome in COVID-19 disease - A multicenter feasibility study.

PURPOSE: Low-dose computed tomography (LDCT) of the chest is a recommended diagnostic tool in early stage of COVID-19 pneumonia. High age, several comorbidities as well as poor physical fitness can negatively influence the outcome within COVID-19 infection. We investigated whether the ratio of fat to muscle area, measured in initial LDCT, can predict severe progression of COVID-19 in the follow-up period. METHOD: We analyzed 58 individuals with confirmed COVID-19 infection that underwent an initial LDCT in one of two included centers due to COVID-19 infection. Using the ratio of waist circumference per paravertebral muscle circumference (FMR), the body composition was estimated. Patient outcomes were rated on an ordinal scale with higher numbers representing more severe progression or disease associated complications (hospitalization/ intensive care unit (ICU)/ tracheal intubation/ death) within a follow-up period of 22 days after initial LDCT. RESULTS: In the initial LDCT a significantly higher FMR was found in patients requiring intensive care treatment within the follow-up period. In multivariate logistic regression analysis, FMR (p < .001) in addition to age (p < .01), was found to be a significant predictor of the necessity for ICU treatment of COVID-19 patients. CONCLUSION: FMR as potential surrogate of body composition and obesity can be easily determined in initial LDCT of COVID-19 patients. Within the multivariate analysis, in addition to patient age, low muscle area in proportion to high fat area represents an additional prognostic information for the patient outcome and the need of an ICU treatment during the follow-up period within the next 22 days. This multicentric pilot study presents a method using an initial LDCT to screen opportunistically for obese patients who have an increased risk for the need of ICU treatment. While clinical capacities, such as ICU beds and ventilators, are more crucial than ever to help manage the current global corona pandemic, this work introduces an approach that can be used for a cost-effective way to help determine the amount of these rare clinical resources required in the near future.