Case 291.

History A 46-year-old woman with known mixed connective tissue disease with clinical features of scleroderma and polymyositis and who was not on specific medications was referred to our institution to assess for interstitial lung disease due to her predisposing condition. She was a nonsmoker, had no respiratory symptoms, and enjoyed good exercise tolerance. She did not have any cutaneous lesions or renal disease. There was no family history of pulmonary or systemic disease. Her routine blood test results revealed a white blood cell count of 4.6 × 109/L (normal range, [4.4-10.1] × 109/L), a hemoglobin level of 7.76 mmol/L (normal range, 7.26-9.18 mmol/L), a platelet count of 189 × 109/L (normal range, [170-380] × 109/L), a bilirubin level of 8 µmol/L (7-19 µmol/L), and a creatinine level of 63 µmol/L (45-82 µmol/L), all within normal limits. Lung function tests at presentation yielded normal results, with a diffusing capacity for carbon monoxide of 95% and a forced vital capacity of 2.29 (98% predicted value). However, this patient had an elevated serum globulin level of 47 g/L (normal range, 26-32 g/L) and an erythrocyte sedimentation rate of 36 mm/h (normal range, 0-20 mm/h), while C-reactive protein level was normal at less than 0.35 mg/dL. She was seropositive for antinuclear (titer >1/720), anti-Ro, anti-La, and anti-extractable nuclear antigen antibodies. Chest radiography and CT were performed at presentation (Figs 1, 2) and 14-year follow-up (Figs 3, 4). PET/CT was performed at 7- (Fig 5, A and B) and 13-year follow-up (Fig 5, C and D). Throughout this 14-year follow-up period, she remained completely free of respiratory symptoms and continued to go for a brisk walk every day. At 14-year follow-up, there was no substantial change in serum laboratory values, but a lung function test revealed her diffusing capacity for carbon monoxide had decreased to 52%, while her forced vital capacity remained good at 95%; these findings were suggestive of interval development of restrictive lung function.

Case 291: Amyloid-associated Cystic Lung Disease and Coexistent Mucosa-associated Lymphoid Tissue Lymphoma.

History A 46-year-old woman with known mixed connective tissue disease with clinical features of scleroderma and polymyositis and who was not on specific medications was referred to our institution to assess for interstitial lung disease due to her predisposing condition. She was a nonsmoker, had no respiratory symptoms, and enjoyed good exercise tolerance. She did not have any cutaneous lesions or renal disease. There was no family history of pulmonary or systemic disease. Her routine blood test results revealed a white blood cell count of 4.6 × 109/L (normal range, [4.4-10.1] × 109/L), a hemoglobin level of 7.76 mmol/L (normal range, 7.26-9.18 mmol/L), a platelet count of 189 × 109/L (normal range, [170-380] × 109/L), a bilirubin level of 8 mmol/L (normal range, <19 mmol/L), and a creatinine level of 63 mmol/L (normal range, 45-82 mmol/L), all within normal limits. Lung function tests at presentation yielded normal results, with a diffusing capacity for carbon monoxide of 95% and a forced vital capacity of 2.29 (98% predicted value). However, this patient had an elevated serum globulin level of 47 g/L (normal range, 26-32 g/L) and an erythrocyte sedimentation rate of 36 mm/h (normal range, 0-20 mm/h), while C-reactive protein level was normal at less than 0.35 mg/dL. She was seropositive for antinuclear (titer >1/720), anti-Ro, anti-La, and anti-extractable nuclear antigen antibodies. Chest radiography and CT were performed at presentation and 14-year follow-up. PET/CT was performed at 7- and 13-year follow-up. Throughout this 14-year follow-up period, she remained completely free of respiratory symptoms and continued to go for a brisk walk every day. At 14-year follow-up, there was no substantial change in serum laboratory values, but a lung function test revealed her diffusing capacity for carbon monoxide had decreased to 52%, while her forced vital capacity remained good at 95%; these findings were suggestive of interval development of restrictive lung function.

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19.

Background Current coronavirus disease 2019 (COVID-19) radiologic literature is dominated by CT, and a detailed description of chest radiography appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of findings of COVID-19 at chest radiography and correlate these with real-time reverse transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, nucleic acid. Materials and Methods This is a retrospective study of patients with COVID-19 confirmed by using RT-PCR and chest radiographic examinations who were admitted across four hospitals and evaluated between January and March 2020. Baseline and serial chest radiographs (n = 255) were reviewed with RT-PCR. Correlation with concurrent CT examinations (n = 28) was performed when available. Two radiologists scored each chest radiograph in consensus for consolidation, ground-glass opacity, location, and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. Results The study was composed of 64 patients (26 men; mean age, 56 years ± 19 [standard deviation]). Of these, 58 patients had initial positive findings with RT-PCR (91%; 95% confidence interval: 81%, 96%), 44 patients had abnormal findings at baseline chest radiography (69%; 95% confidence interval: 56%, 80%), and 38 patients had initial positive findings with RT-PCR testing and abnormal findings at baseline chest radiography (59%; 95% confidence interval: 46%, 71%). Six patients (9%) showed abnormalities at chest radiography before eventually testing positive for COVID-19 with RT-PCR. Sensitivity of initial RT-PCR (91%; 95% confidence interval: 83%, 97%) was higher than that of baseline chest radiography (69%; 95% confidence interval: 56%, 80%) (P = .009). Radiographic recovery (mean, 6 days ± 5) and virologic recovery (mean, 8 days ± 6) were not significantly different (P = .33). Consolidation was the most common finding (30 of 64; 47%) followed by ground-glass opacities (21 of 64; 33%). Abnormalities at chest radiography had a peripheral distribution (26 of 64; 41%) and lower zone distribution (32 of 64; 50%) with bilateral involvement (32 of 64; 50%). Pleural effusion was uncommon (two of 64; 3%). The severity of findings at chest radiography peaked at 10-12 days from the date of symptom onset. Conclusion Findings at chest radiography in patients with coronavirus disease 2019 frequently showed bilateral lower zone consolidation, which peaked at 10-12 days from symptom onset. © RSNA, 2020.

Discrimination of pulmonary ground-glass opacity changes in COVID-19 and non-COVID-19 patients using CT radiomics analysis.

PURPOSE: The coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic. CT although sensitive in detecting changes suffers from poor specificity in discrimination from other causes of ground glass opacities (GGOs). We aimed to develop and validate a CT-based radiomics model to differentiate COVID-19 from other causes of pulmonary GGOs. METHODS: We retrospectively included COVID-19 patients between 24/01/2020 and 31/03/2020 as case group and patients with pulmonary GGOs between 04/02/2012 and 31/03/2020 as a control group. Radiomics features were extracted from contoured GGOs by PyRadiomics. The least absolute shrinkage and selection operator method was used to establish the radiomics model. We assessed the performance using the area under the curve of the receiver operating characteristic curve (AUC). RESULTS: A total of 301 patients (age mean ±â€¯SD: 64 ±â€¯15 years; male: 52.8 %) from three hospitals were enrolled, including 33 COVID-19 patients in the case group and 268 patients with malignancies or pneumonia in the control group. Thirteen radiomics features out of 474 were selected to build the model. This model achieved an AUC of 0.905, accuracy of 89.5 %, sensitivity of 83.3 %, specificity of 90.0 % in the testing set. CONCLUSION: We developed a noninvasive radiomics model based on CT imaging for the diagnosis of COVID-19 based on GGO lesions, which could be a promising supplementary tool for improving specificity for COVID-19 in a population confounded by ground glass opacity changes from other etiologies.

Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2.

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.

Development and validation of risk prediction models for COVID-19 positivity in a hospital setting.

OBJECTIVES: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. METHODS: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on the H-L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. CONCLUSION: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

Development and validation of an imaging and clinical scoring system to predict early mortality in spontaneous ruptured hepatocellular carcinoma treated with transarterial embolization.

PURPOSE: To develop and validate a scoring system using a combination of imaging and clinical parameters to predict 30-day mortality in ruptured HCC (rHCC) patients after transarterial embolization (TAE). METHODS: 98 consecutive patients with rHCC who underwent abdominal CT and subsequent TAE between January 2007 and December 2016 were retrospectively reviewed. The CT scans were reviewed by two radiologists blinded to the patient outcome. Clinical parameters including serum bilirubin, albumin, INR, creatinine, and hemoglobin were recorded. Independent risk factors for 30-day mortality after TAE were identified using multivariate binary logistic regression, for development of a scoring system. The scoring system was then validated in 20 patients between January 2017 and May 2018. RESULTS: In the development cohort, bilobar tumor distribution (OR = 29.6), clinical parameters of bilirubin > 2.5 mg/dL (OR = 5.9), and albumin < 30 g/L (OR = 4.1) were independent predictors for 30-day mortality. A 6-point score was derived and yielded area-under-the-receiver-operating-characteristic-curve (AUC) of 0.904. A score ≥ 4 resulted in sensitivity of 80.5% and specificity of 91.2% for 30-day mortality. In the validation cohort, AUC for 30-day mortality was 0.939. A score ≥ 4 resulted in sensitivity of 81.2% and specificity of 88.9%. In both development and validation cohorts, the proposed scoring system was better than biochemical components of Child-Pugh score and serum bilirubin to predict 30-day mortality. CONCLUSION: Imaging and clinical parameters can be combined into a scoring system to accurately predict 30-day mortality after TAE in rHCC patients. The score may help identify and counsel high-risk patients.

The IVC contrast level sign.

The inferior vena cava (IVC) contrast level sign refers to a contrast-fluid level seen in the IVC on an arterial phase contrast-enhanced computed tomography (CT) scan. This sign has been documented in conditions including cardiac tamponade, myocardial infarction, and cardiac arrest. When this sign is detected, the patient requires immediate attention, with resuscitation initiated as needed, and the referring clinician alerted as soon as possible.

Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells.

The miR-17-92 locus encodes a cluster of 7 microRNAs transcribed as a single primary transcript. It can accelerate c-Myc induced B cell lymphoma development and is highly expressed in many tumors, including lung tumors. However, the role of miR-17-92 in development has not been well studied. From analysis of microRNAs during lung development, expression of the miR-17-92 cluster is high at early stages, but declines as development proceeds. We used the mouse surfactant protein C (Sftpc) promoter to over-express the cluster in embryonic lung epithelium. Transgenic lungs have a very abnormal lethal phenotype. They contain numerous proliferative epithelial cells that retain high levels of Sox9, a marker of distal progenitors. The differentiation of proximal epithelial cells was also inhibited. Furthermore, a significant increase in the number of neuroendocrine cell clusters was observed in the lungs of dead transgenic pups. We identify a tumor suppressor, Rbl2 which belongs to the Rb family, as a new target for miR-17-5p. Together, these studies suggest that mir-17-92 normally promotes the high proliferation and undifferentiated phenotype of lung epithelial progenitor cells.