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All Publications

  • Sarcopenia, Precardial Adipose Tissue and High Tumor Volume as Outcome Predictors in Surgically Treated Pleural Mesothelioma DIAGNOSTICS Verhoek, O., Jungblut, L., Lauk, O., Bluethgen, C., Opitz, I., Frauenfelder, T., Martini, K. 2022; 12 (1)


    We evaluated the prognostic value of Sarcopenia, low precardial adipose-tissue (PAT), and high tumor-volume in the outcome of surgically-treated pleural mesothelioma (PM).From 2005 to 2020, consecutive surgically-treated PM-patients having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by CT-based parameters measured at the level of the fifth thoracic vertebra (TH5) by excluding fatty-infiltration based on CT-attenuation. The findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Additionally, tumor volume as well as PAT were measured. The findings were correlated with progression-free survival and long-term mortality.Two-hundred-seventy-eight PM-patients (252 male; 70.2 ± 9 years) were included. The mean progression-free survival was 18.6 ± 12.2 months, and the mean survival time was 23.3 ± 24 months. Progression was associated with chronic obstructive pulmonary disease (COPD) (p = <0.001), tumor-stage (p = 0.001), and type of surgery (p = 0.026). Three-year mortality was associated with higher patient age (p = 0.005), presence of COPD (p < 0.001), higher tumor-stage (p = 0.015), and higher tumor-volume (p < 0.001). Kaplan-Meier statistics showed that sarcopenic patients have a higher three-year mortality (p = 0.002). While there was a negative correlation of progression-free survival and mortality with tumor volume (r = 0.281, p = 0.001 and r = -0.240, p < 0.001; respectively), a correlation with PAT could only be shown for epithelioid PM (p = 0.040).Sarcopenia as well as tumor volume are associated with long-term mortality in surgically treated PM-patients. Further, while there was a negative correlation of progression-free survival and mortality with tumor volume, a correlation with PAT could only be shown for epithelioid PM.

    View details for DOI 10.3390/diagnostics12010099

    View details for Web of Science ID 000747318800001

    View details for PubMedID 35054268

    View details for PubMedCentralID PMC8774409

  • Computed tomography-based radiomics decodes prognostic and molecular differences in interstitial lung disease related to systemic sclerosis. The European respiratory journal Schniering, J., Maciukiewicz, M., Gabrys, H. S., Brunner, M., Bluthgen, C., Meier, C., Braga-Lagache, S., Uldry, A., Heller, M., Guckenberger, M., Fretheim, H., Nakas, C. T., Hoffmann-Vold, A., Distler, O., Frauenfelder, T., Tanadini-Lang, S., Maurer, B. 2021


    BACKGROUND: Radiomic features calculated from routine medical images show great potential for personalized medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multi-organ autoimmune disorder, have a similarly poor prognosis due to interstitial lung disease (ILD).OBJECTIVES: To explore computed tomography (CT)-based high-dimensional image analysis (radiomics) for disease characterisation, risk stratification, and relaying information on lung pathophysiology in SSc-ILD.METHODS: We investigated two independent, prospectively followed SSc-ILD cohorts (Zurich, derivation cohort, n=90; Oslo, validation cohort, n=66). For every subject, we defined 1'355 robust radiomic features from standard-of-care CT images. We performed unsupervised clustering to identify and characterize imaging-based patient clusters. A clinically applicable prognostic quantitative radiomic risk score (qRISSc) for progression-free survival was derived from radiomic profiles using supervised analysis. The biological basis of qRISSc was assessed in a cross-species approach by correlation with lung proteomics, histological and gene expression data derived from mice with bleomycin-induced lung fibrosis.RESULTS: Radiomic profiling identified two clinically and prognostically distinct SSc-ILD patient clusters. To evaluate the clinical applicability, we derived and externally validated a binary, quantitative radiomic risk score composed of 26 features, qRISSc, that accurately predicted progression-free survival and significantly improved upon clinical risk stratification parameters in multivariable Cox regression analyses in the pooled cohorts. A high qRISSc score, which identifies patients at risk for progression, was reverse translatable from human to experimental ILD and correlated with fibrotic pathway activation.CONCLUSIONS: Radiomics-based risk stratification using routine CT images provides complementary phenotypic, clinical and prognostic information significantly impacting clinical decision-making in SSc-ILD.

    View details for DOI 10.1183/13993003.04503-2020

    View details for PubMedID 34649979

  • First Performance Evaluation of an Artificial Intelligence-Based Computer-Aided Detection System for Pulmonary Nodule Evaluation in Dual-Source Photon-Counting Detector CT at Different Low-Dose Levels. Investigative radiology Jungblut, L., Bluthgen, C., Polacin, M., Messerli, M., Schmidt, B., Euler, A., Alkadhi, H., Frauenfelder, T., Martini, K. 2021


    OBJECTIVE: The aim of this study was to evaluate the image quality (IQ) and performance of an artificial intelligence (AI)-based computer-aided detection (CAD) system in photon-counting detector computed tomography (PCD-CT) for pulmonary nodule evaluation at different low-dose levels.MATERIALS AND METHODS: An anthropomorphic chest-phantom containing 14 pulmonary nodules of different sizes (range, 3-12 mm) was imaged on a PCD-CT and on a conventional energy-integrating detector CT (EID-CT). Scans were performed with each of the 3 vendor-specific scanning modes (QuantumPlus [Q+], Quantum [Q], and High Resolution [HR]) at decreasing matched radiation dose levels (volume computed tomography dose index ranging from 1.79 to 0.31 mGy) by adapting IQ levels from 30 to 5. Image noise was measured manually in the chest wall at 8 different locations. Subjective IQ was evaluated by 2 readers in consensus. Nodule detection and volumetry were performed using a commercially available AI-CAD system.RESULTS: Subjective IQ was superior in PCD-CT compared with EID-CT (P < 0.001), and objective image noise was similar in the Q+ and Q-mode (P > 0.05) and superior in the HR-mode (PCD 55.8 ± 11.7 HU vs EID 74.8 ± 5.4 HU; P = 0.01). High resolution showed the lowest image noise values among PCD modes (P = 0.01). Overall, the AI-CAD system delivered comparable results for lung nodule detection and volumetry between PCD- and dose-matched EID-CT (P = 0.08-1.00), with a mean sensitivity of 95% for PCD-CT and of 86% for dose-matched EID-CT in the lowest evaluated dose level (IQ5). Q+ and Q-mode showed higher false-positive rates than EID-CT at lower-dose levels (IQ10 and IQ5). The HR-mode showed a sensitivity of 100% with a false-positive rate of 1 even at the lowest evaluated dose level (IQ5; CDTIvol, 0.41 mGy).CONCLUSIONS: Photon-counting detector CT was superior to dose-matched EID-CT in subjective IQ while showing comparable to lower objective image noise. Fully automatized AI-aided nodule detection and volumetry are feasible in PCD-CT, but attention has to be paid to false-positive findings.

    View details for DOI 10.1097/RLI.0000000000000814

    View details for PubMedID 34324462

  • Impact of Vessel Suppressed-CT on Diagnostic Accuracy in Detection of Pulmonary Metastasis and Reading Time ACADEMIC RADIOLOGY Martini, K., Bluethgen, C., Eberhard, M., Schoenenberger, A. N., De Martini, Huber, F. A., Barth, B. K., Euler, A., Frauenfelder, T. 2021; 28 (7): 988-994


    To assess if vessel suppression (VS) improves nodule detection rate, interreader agreement, and reduces reading time in oncologic chest computed tomography (CT).One-hundred consecutive oncologic patients (65 male; median age 60y) who underwent contrast-enhanced chest CT were retrospectively included. For all exams, additional VS series (ClearRead CT, Riverrain Technologies, Miamisburg) were reconstructed. Two groups of three radiologists each with matched experience were defined. Each group evaluated the SD-CT as well as VS-CT. Each reader marked the presence, size, and position of pulmonary nodules and documented reading time. In addition, for the VS-CT the presence of false positive nodules had to be stated. Cohen's Kappa (k) was used to calculate the interreader-agreement between groups. Reading time was compared using paired t test.Nodule detection rate was significantly higher in VS-CT compared to the SD-CT (+21%; p <0.001). Interreader-agreement was higher in the VS-CT (k = 0.431, moderate agreement) compared to SD-CT (k = 0.209, fair agreement). Almost all VS-CT series had false positive findings (97-99 out of 100). Average reading time was significantly shorter in the VS-CT compared to the SD-CT (154 ± 134vs. 194 ± 126; 21%, p<0.001).Vessel suppression increases nodule detection rate, improves interreader agreement, and reduces reading time in chest CT of oncologic patients. Due to false positive results a consensus reading with the SD-CT is essential.

    View details for DOI 10.1016/j.acra.2020.01.014

    View details for Web of Science ID 000669231400018

    View details for PubMedID 32037256

  • Lung Nodules in Melanoma Patients: Morphologic Criteria to Differentiate Non-Metastatic and Metastatic Lesions DIAGNOSTICS Stadelmann, S., Bluethgen, C., Milanese, G., Nguyen-Kim, T., Maul, J., Dummer, R., Frauenfelder, T., Eberhard, M. 2021; 11 (5)


    Lung nodules are frequent findings in chest computed tomography (CT) in patients with metastatic melanoma. In this study, we assessed the frequency and compared morphologic differences of metastases and benign nodules. We retrospectively evaluated 85 patients with melanoma (AJCC stage III or IV). Inclusion criteria were ≤20 lung nodules and follow-up using CT ≥183 days after baseline. Lung nodules were evaluated for size and morphology. Nodules with significant growth, nodule regression in line with RECIST assessment or histologic confirmation were judged to be metastases. A total of 438 lung nodules were evaluated, of which 68% were metastases. At least one metastasis was found in 78% of patients. A 10 mm diameter cut-off (used for RECIST) showed a specificity of 95% and a sensitivity of 20% for diagnosing metastases. Central location (n = 122) was more common in metastatic nodules (p = 0.009). Subsolid morphology (n = 53) was more frequent (p < 0.001), and calcifications (n = 13) were solely found in non-metastatic lung nodules (p < 0.001). Our data show that lung nodules are prevalent in about two-thirds of melanoma patients (AJCC stage III/IV) and the majority are metastases. Even though we found a few morphologic indicators for metastatic or non-metastatic lung nodules, morphology has limited value to predict the presence of lung metastases.

    View details for DOI 10.3390/diagnostics11050837

    View details for Web of Science ID 000653820400001

    View details for PubMedID 34066913

    View details for PubMedCentralID PMC8148527

  • Computed tomography radiomics for the prediction of thymic epithelial tumor histology, TNM stage and myasthenia gravis. PloS one Bluthgen, C., Patella, M., Euler, A., Baessler, B., Martini, K., von Spiczak, J., Schneiter, D., Opitz, I., Frauenfelder, T. 1800; 16 (12): e0261401


    OBJECTIVES: To evaluate CT-derived radiomics for machine learning-based classification of thymic epithelial tumor (TET) stage (TNM classification), histology (WHO classification) and the presence of myasthenia gravis (MG).METHODS: Patients with histologically confirmed TET in the years 2000-2018 were retrospectively included, excluding patients with incompatible imaging or other tumors. CT scans were reformatted uniformly, gray values were normalized and discretized. Tumors were segmented manually; 15 scans were re-segmented after 2 weeks by two readers. 1316 radiomic features were calculated (pyRadiomics). Features with low intra-/inter-reader agreement (ICC<0.75) were excluded. Repeated nested cross-validation was used for feature selection (Boruta algorithm), model training, and evaluation (out-of-fold predictions). Shapley additive explanation (SHAP) values were calculated to assess feature importance.RESULTS: 105 patients undergoing surgery for TET were identified. After applying exclusion criteria, 62 patients (28 female; mean age, 57±14 years; range, 22-82 years) with 34 low-risk TET (LRT; WHO types A/AB/B1), 28 high-risk TET (HRT; WHO B2/B3/C) in early stage (49, TNM stage I-II) or advanced stage (13, TNM III-IV) were included. 14(23%) of the patients had MG. 334(25%) features were excluded after intra-/inter-reader analysis. Discriminatory performance of the random forest classifiers was good for histology(AUC, 87.6%; 95% confidence interval, 76.3-94.3) and TNM stage(AUC, 83.8%; 95%CI, 66.9-93.4) but poor for the prediction of MG (AUC, 63.9%; 95%CI, 44.8-79.5).CONCLUSIONS: CT-derived radiomic features may be a useful imaging biomarker for TET histology and TNM stage.

    View details for DOI 10.1371/journal.pone.0261401

    View details for PubMedID 34928978

  • Accuracy of Conventional and Machine Learning Enhanced Chest Radiography for the Assessment of COVID-19 Pneumonia: Intra-Individual Comparison with CT JOURNAL OF CLINICAL MEDICINE Martini, K., Bluethgen, C., Walter, J. E., Messerli, M., Nguyen-Kim, T., Frauenfelder, T. 2020; 9 (11)


    To evaluate diagnostic accuracy of conventional radiography (CXR) and machine learning enhanced CXR (mlCXR) for the detection and quantification of disease-extent in COVID-19 patients compared to chest-CT.Real-time polymerase chain reaction (rt-PCR)-confirmed COVID-19-patients undergoing CXR from March to April 2020 together with COVID-19 negative patients as control group were retrospectively included. Two independent readers assessed CXR and mlCXR images for presence, disease extent and type (consolidation vs. ground-glass opacities (GGOs) of COVID-19-pneumonia. Further, readers had to assign confidence levels to their diagnosis. CT obtained ≤ 36 h from acquisition of CXR served as standard of reference. Inter-reader agreement, sensitivity for detection and disease extent of COVID-19-pneumonia compared to CT was calculated. McNemar test was used to test for significant differences.Sixty patients (21 females; median age 61 years, range 38-81 years) were included. Inter-reader agreement improved from good to excellent when mlCXR instead of CXR was used (k = 0.831 vs. k = 0.742). Sensitivity for pneumonia detection improved from 79.5% to 92.3%, however, on the cost of specificity 100% vs. 71.4% (p = 0.031). Overall, sensitivity for the detection of consolidation was higher than for GGO (37.5% vs. 70.4%; respectively). No differences could be found in disease extent estimation between mlCXR and CXR, even though the detection of GGO could be improved. Diagnostic confidence was better on mlCXR compared to CXR (p = 0.013).In line with the current literature, the sensitivity for detection and quantification of COVID-19-pneumonia was moderate with CXR and could be improved when mlCXR was used for image interpretation.

    View details for DOI 10.3390/jcm9113576

    View details for Web of Science ID 000593269200001

    View details for PubMedID 33171999

    View details for PubMedCentralID PMC7694629

  • Sarcopenia as independent risk factor of postpneumonectomy respiratory failure, ARDS and mortality LUNG CANCER Martini, K., Chassagnon, G., Fournel, L., Prieto, M., Trieu-Nghi Hoang-Thi, Halm, N., Bobbio, A., Revel, M., Alifano, M. 2020; 149: 130-136


    Sarcopenia is associated with poor outcome in cancer-patients. However, the methods to define sarcopenia are not entirely standardized. We compared several morphometric measurements of sarcopenia and their prognostic value in short-term-outcome prediction after pneumonectomy.Consecutive lung-cancer patients undergoing pneumonectomy from January 2007 to December 2015 and having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by the following CT-based parameters measured at the level of the third lumbar vertebra: cross-sectional Total Psoas Area (TPA), cross-sectional Total Muscle Area (TMA), and Total Parietal Muscle Area (TPMA), defined as TMA without TPA. Measures were obtained for entire muscle surface, as well as by excluding fatty infiltration based on CT attenuation. Findings were stratified for gender, and a threshold of 33rd percentile was set to define sarcopenia. Acute Respiratory Failure (ARF), Acute Respiratory Distress Syndrome (ARDS), and 30-day mortality were assessed as parameters of short-term-outcome.Two hundred thirty-four patients with pneumonectomy (right, n = 107; left, n = 127) were analysed. Postoperative mortality rate was 9.0 % (21/234), 17.1 % of patients (40/234) experienced ARF requiring re-intubation, and 10.3 % (24/234) had ARDS. All parameters describing sarcopenia gave significant results; the best discriminating parameter was TMA after excluding fat (p < 0.001). While right sided pneumonectomy and sarcopenia were independently associated to the three short-term outcome parameters, Charlson Comorbidity Index only independently predicted ARF.Sarcopenia defined as the sex-related 33rd percentile of fat-excluded TMA at the level of the third lumbar vertebra is the most discriminating parameter to assess short-term-outcome in patients undergoing pneumonectomy.

    View details for DOI 10.1016/j.lungcan.2020.09.009

    View details for Web of Science ID 000579504300019

    View details for PubMedID 33011374

  • Brown fat does not cause cachexia in cancer patients: A large retrospective longitudinal FDG-PET/CT cohort study PLOS ONE Becker, A. S., Zellweger, C., Bacanovic, S., Franckenberg, S., Nagel, H. W., Frick, L., Schawkat, K., Eberhard, M., Bluethgen, C., Volbracht, J., Moos, R., Wolfrum, C., Burger, I. A. 2020; 15 (10): e0239990


    Brown adipose tissue (BAT) is a specialized form of adipose tissue, able to increase energy expenditure by heat generation in response to various stimuli. Recently, its pathological activation has been implicated in the pathogenesis of cancer cachexia. To establish a causal relationship, we retrospectively investigated the longitudinal changes in BAT and cancer in a large FDG-PET/CT cohort.We retrospectively analyzed 13 461 FDG-PET/CT examinations of n = 8 409 patients at our institution from the winter months of 2007-2015. We graded the activation strength of BAT based on the anatomical location of the most caudally activated BAT depot into three tiers, and the stage of the cancer into five general grades. We validated the cancer grading by an interreader analysis and correlation with histopathological stage. Ambient temperature data (seven-day average before the examination) was obtained from a meteorological station close to the hospital. Changes of BAT, cancer, body mass index (BMI) and temperature between the different examinations were examined with Spearman's test and a mixed linear model for correlation, and with a causal inference algorithm for causality.We found n = 283 patients with at least two examinations and active BAT in at least one of them. There was no significant interaction between the changes in BAT activation, cancer burden or BMI. Temperature changes exhibited a strong negative correlation with BAT activity (ϱ = -0.57, p<0.00001). These results were confirmed with the mixed linear model. Causal inference revealed a link of Temperature ➜ BAT in all subjects and also of BMI ➜ BAT in subjects who had lost weight and increased cancer burden, but no role of cancer and no causal links of BAT ➜ BMI.Our data did not confirm the hypothesis that BAT plays a major role in cancer-mediated weight loss. Temperature changes are the main driver of incidental BAT activity on FDG-PET scans.

    View details for DOI 10.1371/journal.pone.0239990

    View details for Web of Science ID 000581809800092

    View details for PubMedID 33031379

    View details for PubMedCentralID PMC7544086

  • Applicability of radiomics in interstitial lung disease associated with systemic sclerosis: proof of concept EUROPEAN RADIOLOGY Martini, K., Baessler, B., Bogowicz, M., Bluthgen, C., Mannil, M., Tanadini-Lang, S., Schniering, J., Maurer, B., Frauenfelder, T. 2021; 31 (4): 1987-1998


    To retrospectively evaluate if texture-based radiomics features are able to detect interstitial lung disease (ILD) and to distinguish between the different disease stages in patients with systemic sclerosis (SSc) in comparison with mere visual analysis of high-resolution computed tomography (HRCT).Sixty patients (46 females, median age 56 years) with SSc who underwent HRCT of the thorax were retrospectively analyzed. Visual analysis was performed by two radiologists for the presence of ILD features. Gender, age, and pulmonary function (GAP) stage was calculated from clinical data (gender, age, pulmonary function test). Data augmentation was performed and the balanced dataset was split into a training (70%) and a testing dataset (30%). For selecting variables that allow classification of the GAP stage, single and multiple logistic regression models were fitted and compared by using the Akaike information criterion (AIC). Diagnostic accuracy was evaluated from the area under the curve (AUC) from receiver operating characteristic (ROC) analyses, and diagnostic sensitivity and specificity were calculated.Values for some radiomics features were significantly lower (p < 0.05) and those of other radiomics features were significantly higher (p = 0.001) in patients with GAP2 compared with those in patients with GAP1. The combination of two specific radiomics features in a multivariable model resulted in the lowest AIC of 10.73 with an AUC of 0.96, 84% sensitivity, and 99% specificity. Visual assessment of fibrosis was inferior in predicting individual GAP stages (AUC 0.86; 83% sensitivity; 74% specificity).The correlation of radiomics with GAP stage, but not with the visually defined features of ILD-HRCT, implies that radiomics might capture features indicating severity of SSc-ILD on HRCT, which are not recognized by visual analysis.• Radiomics features can predict GAP stage with a sensitivity of 84% and a specificity of almost 100%. • Extent of fibrosis on HRCT and a combined model of different visual HRCT-ILD features perform worse in predicting GAP stage. • The correlation of radiomics with GAP stage, but not with the visually defined features of ILD-HRCT, implies that radiomics might capture features on HRCT, which are not recognized by visual analysis.

    View details for DOI 10.1007/s00330-020-07293-8

    View details for Web of Science ID 000575746000001

    View details for PubMedID 33025174

    View details for PubMedCentralID PMC7979612

  • Comparison of the PI-RADS 2.1 scoring system to PI-RADS 2.0: Impact on diagnostic accuracy and inter-reader agreement PLOS ONE Hotker, A. M., Bluthgen, C., Rupp, N. J., Schneider, A. F., Eberli, D., Donati, O. F. 2020; 15 (10): e0239975


    To assess the value of the PI-RADS 2.1 scoring system in the detection of prostate cancer on multiparametric MRI in comparison to the standard PI-RADS 2.0 system and to assess its inter-reader variability.This IRB-approved study included 229 patients undergoing multiparametric prostate MRI prior to MRI-guided TRUS-based biopsy, which were retrospectively recruited from our prospectively maintained institutional database. Two readers with high (reader 1, 6 years) and low (reader 2, 2 years) level of expertise identified the lesion with the highest PI-RADS score for both version 2.0 and 2.1 for each patient. Inter-reader agreement was estimated, and diagnostic accuracy analysis was performed.Inter-reader agreement on PI-RADS scores was fair for both version 2.0 (kappa: 0.57) and 2.1 (kappa: 0.51). Detection rates for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) were almost identical for both PI-RADS versions and higher for the more experienced reader (AUC, Reader 1: PCa, 0.881-0.887, csPCa, 0.874-0.879; Reader 2: PCa, 0.765, csPCa, 0.746-0.747; both p > 0.05), both when using a PI-RADS score of ≥ 4 and ≥3 as indicators for positivity for cancer.The new PI-RADS 2.1 scoring system showed comparable diagnostic performance and inter-reader variability compared to version 2.0. The introduced changes in the version 2.1 seem only to take effect in a very small number of patients.

    View details for DOI 10.1371/journal.pone.0239975

    View details for Web of Science ID 000578470500043

    View details for PubMedID 33017413

    View details for PubMedCentralID PMC7535021

  • Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019 PLOS ONE Martini, K., Bluthgen, C., Walter, J., Nguyen-Kim, T., Thienemann, F., Frauenfelder, T. 2020; 15 (10): e0240078


    To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events.Real-time polymerase-chain-reaction (RT-PCR)-confirmed COVID-19 patients undergoing chest-CT (non-enhanced, enhanced, pulmonary-angiography [CT-PA]) from March-April 2020 were retrospectively included (COVID-19-cohort). As control-groups served 175 patients from 2020 (cohort-2020) and 157 patients from 2019 (cohort-2019) undergoing CT-PA for pulmonary embolism (PE) during the respective time frame at our institution. Two independent readers assessed for presence and location of PE in all three cohorts. In COVID-19 patients additionally parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia and OP were assessed. Inter-reader agreement and prevalence of PE in different cohorts were calculated.From 68 COVID-19 patients (42 female [61.8%], median age 59 years [range 32-89]) undergoing chest-CT 38 obtained CT-PA. Inter-reader-agreement was good (k = 0.781). On CT-PA, 13.2% of COVID-19 patients presented with PE whereas in the control-groups prevalence of PE was 9.1% and 8.9%, respectively (p = 0.452). Up to 50% of COVID-19 patients showed changes typical for OP. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA.Despite the reported hypercoagulability in critically ill patients with COVID-19, we did not encounter higher prevalence of PE in our patient cohort compared to the control cohorts. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension.

    View details for DOI 10.1371/journal.pone.0240078

    View details for Web of Science ID 000578470500009

    View details for PubMedID 33017451

    View details for PubMedCentralID PMC7535037

  • Comparison of 3D and 2D late gadolinium enhancement magnetic resonance imaging in patients with acute and chronic myocarditis INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Polacin, M., Kapos, I., Gastl, M., Bluethgen, C., Karolyi, M., von Spiczak, J., Eberhard, M., Baessler, B., Alkadhi, H., Kozerke, S., Manka, R. 2021; 37 (1): 305-313


    We compared a fast, single breath-hold three dimensional LGE sequence (3D LGE) with an established two dimensional multi breath-hold sequence (2D LGE) and evaluated image quality and the amount of myocardial fibrosis in patients with acute and chronic myocarditis. 3D LGE and 2D LGE (both spatial resolution 1.5 × 1.5 mm2, slice-thickness 8 mm, field of view 350 × 350 mm2) were acquired in 25 patients with acute myocarditis (mean age 40 ± 18 years, 7 female) and 27 patients with chronic myocarditis (mean age 44 ± 22 years, 9 female) on a 1.5 T MR system. Image quality was evaluated by two independent, blinded readers using a 5-point Likert scale. Total myocardial mass, fibrotic mass and total fibrotic tissue percentage were quantified for both sequences in both groups. There was no significant difference in image quality between 3D und 2D acquisitions in patients with acute (p = 0.8) and chronic (p = 0.5) myocarditis. No significant differences between 3D and 2D acquisitions could be shown for myocardial mass (acute p = 0.2; chronic p = 0.3), fibrous tissue mass (acute p = 0.7; chronic p = 0.1) and total fibrous percentage (acute p = 0.4 and chronic p = 0.2). Inter-observer agreement was substantial to almost perfect. Acquisition time was significantly shorter for 3D LGE (24 ± 5 s) as compared to 2D LGE (350 ± 58 s, p < 0.001). In patients with acute and chronic myocarditis 3D LGE imaging shows equal diagnostic quality compared to standard 2D LGE imaging but with significantly reduced acquisition time.

    View details for DOI 10.1007/s10554-020-01966-7

    View details for Web of Science ID 000559424600001

    View details for PubMedID 32793996

    View details for PubMedCentralID PMC7878221

  • Deep learning based detection of intracranial aneurysms on digital subtraction angiography: A feasibility study NEURORADIOLOGY JOURNAL Hainc, N., Mannil, M., Anagnostakou, V., Alkadhi, H., Bluthgen, C., Wacht, L., Bink, A., Husain, S., Kulcsar, Z., Winklhofer, S. 2020; 33 (4): 311-317


    Digital subtraction angiography is the gold standard for detecting and characterising aneurysms. Here, we assess the feasibility of commercial-grade deep learning software for the detection of intracranial aneurysms on whole-brain anteroposterior and lateral 2D digital subtraction angiography images.Seven hundred and six digital subtraction angiography images were included from a cohort of 240 patients (157 female, mean age 59 years, range 20-92; 83 male, mean age 55 years, range 19-83). Three hundred and thirty-five (47%) single frame anteroposterior and lateral images of a digital subtraction angiography series of 187 aneurysms (41 ruptured, 146 unruptured; average size 7±5.3 mm, range 1-5 mm; total 372 depicted aneurysms) and 371 (53%) aneurysm-negative study images were retrospectively analysed regarding the presence of intracranial aneurysms. The 2D data was split into testing and training sets in a ratio of 4:1 with 3D rotational digital subtraction angiography as gold standard. Supervised deep learning was performed using commercial-grade machine learning software (Cognex, ViDi Suite 2.0). Monte Carlo cross validation was performed.Intracranial aneurysms were detected with a sensitivity of 79%, a specificity of 79%, a precision of 0.75, a F1 score of 0.77, and a mean area-under-the-curve of 0.76 (range 0.68-0.86) after Monte Carlo cross-validation, run 45 times.The commercial-grade deep learning software allows for detection of intracranial aneurysms on whole-brain, 2D anteroposterior and lateral digital subtraction angiography images, with results being comparable to more specifically engineered deep learning techniques.

    View details for DOI 10.1177/1971400920937647

    View details for Web of Science ID 000546402200001

    View details for PubMedID 32633602

    View details for PubMedCentralID PMC7416354

  • "IMAGES ARE MORE THAN PICTURES, THEY ARE DATA" [1] - EXPLORATION OF RADIOMICS ANALYSIS FOR SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE Schniering, J., Maciukiewicz, M., Gabrys, H., Brunner, M., Bluthgen, C., Distler, O., Guckenberger, M., Frauenfelder, T., Tanadini-Lang, S., Maurer, B. BMJ PUBLISHING GROUP. 2020: 1238-1239
  • Detection and localization of distal radius fractures: Deep learning system versus radiologists EUROPEAN JOURNAL OF RADIOLOGY Bluethgen, C., Becker, A. S., de Martini, I., Meier, A., Martini, K., Frauenfelder, T. 2020; 126: 108925


    To evaluate a deep learning based image analysis software for the detection and localization of distal radius fractures.A deep learning system (DLS) was trained on 524 wrist radiographs (166 showing fractures). Performance was tested on internal (100 radiographs, 42 showing fractures) and external test sets (200 radiographs, 100 showing fractures). Single and combined views of the radiographs were shown to DLS and three readers. Readers were asked to indicate fracture location with regions of interest (ROI). The DLS yielded scores (range 0-1) and a heatmap. Detection performance was expressed as AUC, sensitivity and specificity at the optimal threshold and compared to radiologists' performance. Heatmaps were compared to radiologists' ROIs.The DLS showed excellent performance on the internal test set (AUC 0.93 (95% confidence interval (CI) 0.82-0.98) - 0.96 (0.87-1.00), sensitivity 0.81 (0.58-0.95) - 0.90 (0.70-0.99), specificity 0.86 (0.68-0.96) - 1.0 (0.88-1.0)). DLS performance decreased on the external test set (AUC 0.80 (0.71-0.88) - 0.89 (0.81-0.94), sensitivity 0.64 (0.49-0.77) - 0.92 (0.81-0.98), specificity 0.60 (0.45-0.74) - 0.90 (0.78-0.97)). Radiologists' performance was comparable on internal data (sensitivity 0.71 (0.48-0.89) - 0.95 (0.76-1.0), specificity 0.52 (0.32-0.71) - 0.97 (0.82-1.0)) and better on external data (sensitivity 0.88 (0.76-0.96) - 0.98 (0.89-1.0), specificities 0.66 (0.51-0.79) - 1.0 (0.93-1.0), p < 0.05). In over 90%, the areas of peak activation aligned with radiologists' annotations.The DLS was able to detect and localize wrist fractures with a performance comparable to radiologists, using only a small dataset for training.

    View details for DOI 10.1016/j.ejrad.2020.108925

    View details for Web of Science ID 000525464400014

    View details for PubMedID 32193036

  • Vertical Off-Centering in Reduced Dose Chest-CT: Impact on Effective Dose and Image Noise Values ACADEMIC RADIOLOGY Eberhard, M., Bluethgen, C., Barth, B. K., Frauenfelder, T., Saltybaeva, N., Martini, K. 2020; 27 (4): 508-517


    To assess the effect of vertical off-centering in tube current modulation (TCM) on effective-dose and image-noise in reduced-dose (RD) chest-CT.One-hundred consecutive patients (36 female; mean age 56 years) were scanned on a 192-slice CT scanner with a standard-dose (ND) and a RD chest-CT protocol using tube current modulation. Image-noise was evaluated by placing circular regions of interest in the apical, middle, and lower lung regions. Two independent readers evaluated image quality. Study population was stratified according to patient position in the gantry: positioned in the gantry isocenter (i), higher than the gantry isocenter (ii), and lower than the gantry isocenter, (iii). Pearson correlation was used to determine the correlation between effective radiation dose and vertical off-centering. Student's t test was used to evaluate for differences in image-noise between groups (i-iii).Mean vertical off-centering was of 10.6 mm below the gantry-isocenter (range -45.0-27.9 mm). Effective radiation dose varied in a linear trend, with the highest doses noted below gantry isocenter, and the lowest doses noted above gantry isocenter (ND: r = -0.296; p = 0.003 - RD: r = -0.258; p = 0.010). Lowest image-noise was observed where patients were positioned below the gantry isocenter, and highest in patients positioned above (ND: 79.35 HU vs. 94.86 HU - RD: 143.44 HU vs. 160.13 HU). Subjective image quality was not significantly affected by patient-position (p > 0.05). Overall, there was no over-proportional noise-increase from the ND to the RD protocol in patients which were positioned off-center.Vertical off-centering influences effective radiation dose and image-noise on ND and RD protocols.There is no over-proportional noise increase in RD compared to ND protocols when patients are positioned off-center.

    View details for DOI 10.1016/j.acra.2019.07.004

    View details for Web of Science ID 000520893600010

    View details for PubMedID 31358357

  • Deep learning for automatic quantification of lung abnormalities in COVID-19 patients: First experience and correlation with clinical parameters EUROPEAN JOURNAL OF RADIOLOGY OPEN Mergen, V., Kobe, A., Bluethgen, C., Euler, A., Flohr, T., Frauenfelder, T., Alkadhi, H., Eberhard, M. 2020; 7: 100272


    To demonstrate the first experience of a deep learning-based algorithm for automatic quantification of lung parenchymal abnormalities in chest CT of COVID-19 patients and to correlate quantitative results with clinical and laboratory parameters.We retrospectively included 60 consecutive patients (mean age, 61 ± 12 years; 18 females) with proven COVID-19 infection undergoing chest CT between March and May 2020. Clinical and laboratory data (within 24 h before/after chest CT) were recorded. Prototype software using a deep learning algorithm was applied for automatic segmentation and quantification of lung opacities. Percentage of opacity (PO, ground-glass and consolidations) and percentage of high opacity (PHO, consolidations), were defined as 100 times the volume of segmented abnormalities divided by the volume of the lung mask.Automatic CT analysis of the lung was feasible in all patients (n = 60). The median time to accomplish automatic evaluation was 120 s (IQR: 118-128 s). In four cases (7 %), manual corrections were necessary. Patients with need for mechanical ventilation had a significantly higher PO (median 44 %, IQR: 23-58 % versus 13 %, IQR: 10-24 %; p = 0.001) and PHO (median: 11 %, IQR: 6-21 % versus 3%, IQR: 2-7 %, p = 0.002) compared to those without. The PO and PHO moderately correlated with c-reactive protein (r = 0.49-0.60, both p < 0.001) and leucocyte count (r = 0.30-0.40, both p = 0.05). PO had a negative correlation with SO2 (r=-0.50, p = 0.001).Preliminary experience indicates the feasibility of a rapid, automatic quantification tool of lung parenchymal abnormalities in COVID-19 patients using deep learning, with results correlating with laboratory and clinical parameters.

    View details for DOI 10.1016/j.ejro.2020.100272

    View details for Web of Science ID 000600597400061

    View details for PubMedID 33043101

    View details for PubMedCentralID PMC7538094

  • Can Texture Analysis in Ultrashort Echo-Time MRI Distinguish Primary Graft Dysfunction From Acute Rejection in Lung Transplants? A Multidimensional Assessment in a Mouse Model JOURNAL OF MAGNETIC RESONANCE IMAGING Euler, A., Bluthgen, C., Wurnig, M. C., Jungraithmayr, W., Boss, A. 2020; 51 (1): 108-116


    Differentiation of early postoperative complications affects treatment options after lung transplantation.To assess if texture analysis in ultrashort echo-time (UTE) MRI allows distinction of primary graft dysfunction (PGD) from acute transplant rejection (ATR) in a mouse lung transplant model.Longitudinal.Single left lung transplantation was performed in two cohorts of six mice (strain C57BL/6) receiving six syngeneic (strain C57BL/6) and six allogeneic lung transplants (strain BALB/c (H-2Kd )).4.7T small-animal MRI/eight different UTE sequences (echo times: 50-5000 μs) at three different postoperative timepoints (1, 3, and 7 days after transplantation).Nineteen different first- and higher-order texture features were computed on multiple axial slices for each combination of UTE and timepoint (24 setups) in each mouse. Texture features were compared for transplanted (graft) and contralateral native lungs between and within syngeneic and allogeneic cohorts. Histopathology served as a reference.Nonparametric tests and correlation matrix analysis were used.Pathology revealed PGD in the syngeneic and ATR in the allogeneic cohort. Skewness and low-gray-level run-length features were significantly different between PGD and ATR for all investigated setups (P < 0.03). These features were significantly different between graft and native lung in ATR for most setups (minimum of 20/24 setups; all P < 0.05). The number of significantly different features between PGD and ATR increased with elapsing postoperative time. Differences in significant features were highest for an echo-time of 1500 μs.Our findings suggest that texture analysis in UTE-MRI might be a tool for the differentiation of PGD and ATR in the early postoperative phase after lung transplantation.1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:108-116.

    View details for DOI 10.1002/jmri.26817

    View details for Web of Science ID 000530627200009

    View details for PubMedID 31150142

  • Dual-Energy Low-keV or Single-Energy Low-kV CT for Endoleak Detection? A 6-Reader Study in an Aortic Aneurysm Phantom INVESTIGATIVE RADIOLOGY Skawran, S., Angst, F., Bluthgen, C., Eberhard, M., Kalin, P., Kobe, A., Nagy, D., Szucs-Farkas, Z., Alkadhi, H., Euler, A. 2020; 55 (1): 45-52


    The aim of this study was to compare image quality, conspicuity, and endoleak detection between single-energy low-kV images (SEIs) and dual-energy low-keV virtual monoenergetic images (VMIs+) in computed tomography angiography of the aorta after endovascular repair.An abdominal aortic aneurysm phantom simulating 36 endoleaks (2 densities; diameters: 2, 4, and 6 mm) in a medium- and large-sized patient was used. Each size was scanned using single-energy at 80 kVp (A) and 100 kVp (B), and dual-energy at 80/Sn150kVp for the medium (C) and 90/Sn150kVp for the large size (D). VMIs+ at 40 keV and 50 keV were reconstructed from protocols C and D. Radiation dose was 3 mGy for the medium and 6 mGy for the large size. Objective image quality and normalized noise power spectrum were determined. Subjective image quality, conspicuity, and sensitivity for endoleaks were independently assessed by 6 radiologists. Sensitivity was compared using Marascuilo procedure and Fisher exact test. Conspicuities were compared using Wilcoxon-matched pairs test, analysis of variance, and Tukey test.The contrast-to-noise-ratio of the aorta was significantly higher for VMI+ compared with SEI (P < 0.001). Noise power spectrum showed a higher noise magnitude and coarser texture in VMI+. Subjective image quality and overall conspicuity was lower for VMI+ compared with SEI (P < 0.05). Sensitivity for endoleaks was overall higher in the medium phantom for SEI (60.9% for A, 62.2% for B) compared with VMI+ (54.2% for C, 49.3% for D) with significant differences between protocols B and D (P < 0.05). In the large phantom, there was no significant difference in sensitivity among protocols (P = 0.79), with highest rates for protocols B (31.4%) and C (31.7%).Our study indicates that low-keV VMI+ results in improved contrast-to-noise-ratio of the aorta, whereas noise properties, subjective image quality, conspicuity, and sensitivity for endoleaks were overall superior for SEI.

    View details for DOI 10.1097/RLI.0000000000000606

    View details for Web of Science ID 000503082400007

    View details for PubMedID 31503078

  • Lung cancer screening with submillisievert chest CT: Potential pitfalls of pulmonary findings in different readers with various experience levels EUROPEAN JOURNAL OF RADIOLOGY Martini, K., Ottilinger, T., Serrallach, B., Markart, S., Glaser-Gallion, N., Bluthgen, C., Leschka, S., Bauer, R. W., Wildermuth, S., Messerli, M. 2019; 121: 108720


    To assess the interreader variability of submillisievert CT for lung cancer screening in radiologists with various experience levels.Six radiologists with different degrees of clinical experience in radiology (range, 1-15 years), rated 100 submillisievert CT chest studies as either negative screening finding (no nodules, benign nodules, nodules <5 mm), indeterminate finding (nodules 5-10 mm), positive finding (nodules >10 mm). Each radiologist interpreted scans randomly ordered and reading time was recorded. Interobserver agreement was assessed with ak statistic. Reasons for differences in nodule classification were analysed on a case-by-case basis. Reading time was correlated with reader experience using Pearson correlation (r).The overall interobserver agreement between all readers was moderate (k = 0.454; p < 0.001). In 57 patients, all radiologists agreed on the differentiation of negative and indeterminate/positive finding. In 64 cases disagreement between readers led to different nodule classification. In 8 cases some readers rated the nodule as benign, whereas others scored the case as positive. Overall, disagreement in nodule classification was mostly due to failure in identification of target lesion (n = 40), different lesion measurement (n = 44) or different classification (n = 26). Mean overall reading time per scan was of 2 min 2 s (range: 7s-7 min 45 s) and correlated with reader-experience (r = -0.824).Our study showed substantial interobserver variability for the detection and classification of pulmonary nodules in submillisievert CT. This highlights the importance for careful standardisation of screening programs with the objective of harmonizing efforts of involved radiologists across different institutions by defining and assuring quality standards.

    View details for DOI 10.1016/j.ejrad.2019.108720

    View details for Web of Science ID 000500465900027

    View details for PubMedID 31711024

  • Detection of tuberculosis patterns in digital photographs of chest X-ray images using Deep Learning: feasibility study INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Becker, A. S., Bluthgen, C., Van, V., Sekaggya-Wiltshire, C., Castelnuovo, B., Kambugu, A., Fehr, J., Frauenfelder, T. 2018; 22 (3): 328-+


    To evaluate the feasibility of Deep Learning-based detection and classification of pathological patterns in a set of digital photographs of chest X-ray (CXR) images of tuberculosis (TB) patients.In this prospective, observational study, patients with previously diagnosed TB were enrolled. Photographs of their CXRs were taken using a consumer-grade digital still camera. The images were stratified by pathological patterns into classes: cavity, consolidation, effusion, interstitial changes, miliary pattern or normal examination. Image analysis was performed with commercially available Deep Learning software in two steps. Pathological areas were first localised; detected areas were then classified. Detection was assessed using receiver operating characteristics (ROC) analysis, and classification using a confusion matrix.The study cohort was 138 patients with human immunodeficiency virus (HIV) and TB co-infection (median age 34 years, IQR 28-40); 54 patients were female. Localisation of pathological areas was excellent (area under the ROC curve 0.82). The software could perfectly distinguish pleural effusions from intraparenchymal changes. The most frequent misclassifications were consolidations as cavitations, and miliary patterns as interstitial patterns (and vice versa).Deep Learning analysis of CXR photographs is a promising tool. Further efforts are needed to build larger, high-quality data sets to achieve better diagnostic performance.

    View details for DOI 10.5588/ijtld.17.0520

    View details for Web of Science ID 000429790700016

    View details for PubMedID 29471912

  • Medicina ex Machina: Machine Learning in der Medizin. Praxis Becker, A. S., Bluthgen, C., Muhlematter, U., Boss, A. 2018; 107 (1): 19-23

    View details for DOI 10.1024/1661-8157/a002920

    View details for PubMedID 29295679

  • Economical Sponge Phantom for Teaching, Understanding, and Researching A- and B-Line Reverberation Artifacts in Lung Ultrasound JOURNAL OF ULTRASOUND IN MEDICINE Bluethgen, C., Sanabria, S., Frauenfelder, T., Klingmueller, V., Rominger, M. 2017; 36 (10): 2133-2142


    This project evaluated a low-cost sponge phantom setup for its capability to teach and study A- and B-line reverberation artifacts known from lung ultrasound and to numerically simulate sound wave interaction with the phantom using a finite-difference time-domain (FDTD) model. Both A- and B-line artifacts were reproducible on B-mode ultrasound imaging as well as in the FDTD-based simulation. The phantom was found to be an easy-to-set up and economical tool for understanding, teaching, and researching A- and B-line artifacts occurring in lung ultrasound. The FDTD method-based simulation was able to reproduce the artifacts and provides intuitive insight into the underlying physics.

    View details for DOI 10.1002/jum.14266

    View details for Web of Science ID 000411063300017

    View details for PubMedID 28626903