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OBJECTIVE: This review will focus on how AI—and, specifically, deep learning—can be applied to complement aspects of the current healthcare system. We describe how AI-based tools can augment existing clinical workflows by discussing the applications of AI to worklist prioritization and patient triage, the performance-boosting effects of AI as a second reader, and the use of AI to facilitate complex quantifications. We also introduce prominent examples of recent AI applications, such as tuberculosis screening in resource-constrained environments, the detection of lung cancer with screening CT, and the diagnosis of COVID-19. We also provide examples of prognostic predictions and new discoveries beyond existing clinical practices. BACKGROUND: Artificial intelligence (AI) has shown promising performance for thoracic diseases, particularly in the field of thoracic radiology. However, it has not yet been established how AI-based image analysis systems can help physicians in clinical practice. METHODS: This review included peer-reviewed research articles on AI in the thorax published in English between 2015 and 2021. CONCLUSIONS: With advances in technology and appropriate preparation of physicians, AI could address various clinical problems that have not been solved due to a lack of clinical resources or technological limitations. KEYWORDS: Artificial intelligence (AI); deep learning (DL); computer aided diagnosis (CAD); thoracic radiology; pulmonary medicine

Background A computer-aided detection (CAD) system may help surveillance for pulmonary metastasis at chest radiography in situations where there is limited access to CT. Purpose To evaluate whether a deep learning (DL)-based CAD system can improve diagnostic yield for newly visible lung metastasis on chest radiographs in patients with cancer. Materials and Methods A regulatory-approved CAD system for lung nodules was implemented to interpret chest radiographs from patients referred by the medical oncology department in clinical practice. In this retrospective diagnostic cohort study, chest radiographs interpreted with assistance from a CAD system after the implementation (January to April 2019, CAD-assisted interpretation group) and those interpreted before the implementation (September to December 2018, conventional interpretation group) of the CAD system were consecutively included. The diagnostic yield (frequency of true-positive detections) and false-referral rate (frequency of false-positive detections) of formal reports of chest radiographs for newly visible lung metastasis were compared between the two groups using generalized estimating equations. Propensity score matching was performed between the two groups for age, sex, and primary cancer. Results A total of 2916 chest radiographs from 1521 patients (1546 men, 1370 women; mean age, 62 years) and 5681 chest radiographs from 3456 patients (2941 men, 2740 women; mean age, 62 years) were analyzed in the CAD-assisted interpretation and conventional interpretation groups, respectively. The diagnostic yield for newly visible metastasis was higher in the CAD-assisted interpretation group (0.86%, 25 of 2916 [95% CI: 0.58, 1.3] vs 0.32%, 18 of 568 [95% CI: 0.20, 0.50%]; P = .004). The false-referral rate in the CAD-assisted interpretation group (0.34%, 10 of 2916 [95% CI: 0.19, 0.64]) was not inferior to that in the conventional interpretation group (0.25%, 14 of 5681 [95% CI: 0.15, 0.42]) at the noninferiority margin of 0.5% (95% CI of difference: -0.15, 0.35). Conclusion A deep learning-based computer-aided detection system improved the diagnostic yield for newly visible metastasis on chest radiographs in patients with cancer with a similar false-referral rate. © RSNA, 2021 Online supplemental material is available for this article.

3-hydroxymorphinan (3-HM), a metabolite of dextromethorphan, has previously been reported to have anti-inflammatory, anti-oxidative stress, and neuroprotective effects. However, its effect on energy metabolism in adipocytes remains unclear. Herein, we investigated 3-hydroxymorphinan (3-HM) effects on mitochondrial biogenesis, oxidative stress, and lipid accumulation in 3T3-L1 adipocytes. Further, we explored 3-HM-associated molecular mechanisms. Mouse adipocyte 3T3-L1 cells were treated with 3-HM, and various protein expression levels were determined by western blotting analysis. Mitochondria accumulation and lipid accumulation were measured by staining methods. Cell toxicity was assessed by cell viability assay. We found that treatment of 3T3-L1 adipocytes with 3-HM increased expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). 3-HM promotes mitochondrial biogenesis and its-mediated gene expression. Additionally, 3-HM treatment suppressed mitochondrial ROS generation and superoxide along with improved mitochondrial complex I activity. We found that treatment of 3-HM enhanced AMPK phosphorylation. siRNA-mediated suppression of AMPK reversed all these changes in 3T3-L1 adipocytes. In sum, 3-HM promotes mitochondrial biogenesis and browning and attenuates oxidative stress and lipid accumulation in 3T3-L1 adipocytes via AMPK signaling. Thus, 3-HM-mediated AMPK activation can be considered a therapeutic approach for treating obesity and related diseases.

To explore the value of a deep learning-based algorithm in detecting Lung CT Screening Reporting and Data System category 4 nodules on chest radiographs from an asymptomatic health checkup population. Data from an annual retrospective cohort of individuals who underwent chest radiographs for health checkup purposes and chest CT scanning within 3 months were collected. Among 3073 individuals, 118 with category 4 nodules on CT were selected. A reader performance test was performed using those 118 radiographs and randomly selected 51 individuals without any nodules. Four radiologists independently evaluated the radiographs without and with the results of the algorithm; and sensitivities/specificities were compared. The sample size needed to confirm the difference in detection rates was calculated, i.e., the number of true-positive radiographs divided by the total number of radiographs. The sensitivity of the radiologists substantially increased aided by the algorithm (38.8% [183/472] to 45.1% [213/472]; p 80% power. Although readers substantially increased sensitivity in detecting nodules on chest radiographs from a health checkup population aided by the algorithm, detection rate difference was only 0.24%, requiring a sample size >80,000 for a randomized controlled trial. • Aided by a deep learning algorithm, pooled radiologists improved their sensitivity in detecting Lung-RADS category 4 nodules on chest radiographs from a health checkup population (38.8% [183/472] to 45.1% [213/472]; p < .001), without increasing false-positive rate. • The prevalence of the Lung-RADS category 4 nodules was 3.8% (118/3073) on the population, resulting in only 0.24% increase of the detection rate for the radiologists with assistance of the algorithm. • To confirm the significant detection rate increase by a randomized controlled trial, a sample size of 84,000 would be required.

To develop deep learning–based cardiac chamber enlargement-detection algorithms for left atrial (DLCE-LAE) and ventricular enlargement (DLCE-LVE), on chest radiographs For training and internal validation of DLCE-LAE and -LVE, 5,045 chest radiographs (CRs; 2,463 normal and 2,393 LAE) and 1,012 CRs (456 normal and 456 LVE) matched with the same-day echocardiography were collected, respectively. External validation was performed using 107 temporally independent CRs. Reader performance test was conducted using the external validation dataset by five cardiothoracic radiologists without and with the results of DLCE. Classification performance of DLCE was evaluated and compared with those of the readers and conventional radiographic features, including cardiothoracic ratio, carinal angle, and double contour. In addition, DLCE-LAE was tested on 5,277 CRs from a healthcare screening program cohort. DLCE-LAE showed areas under the receiver operating characteristics curve (AUROCs) of 0.858 on external validation. On reader performance test, DLCE-LAE showed better results than pooled radiologists (AUROC 0.858 vs. 0.651; p < .001) and significantly increased their performance when used as a second reader (AUROC 0.651 vs. 0.722; p < .001). DLCE-LAE also showed a significantly higher AUROC than conventional radiographic findings (AUROC 0.858 vs. 0.535–0.706; all ps < .01). In the healthcare screening cohort, DLCE-LAE successfully detected 71.0% (142/200) CRs with moderate-to-severe LAE (93.5% [29/31] of severe cases), while yielding 11.8% (492/4,184) false-positive rate. DLCE-LVE showed AUROCs of 0.966 and 0.594 on internal and external validation, respectively. DLCE-LAE outperformed and improved cardiothoracic radiologists’ performance in detecting LAE and showed promise in screening individuals with moderate-to-severe LAE in a healthcare screening cohort. • Our deep learning algorithm outperformed cardiothoracic radiologists in detecting left atrial enlargement on chest radiographs. • Cardiothoracic radiologists improved their performance in detecting left atrial enlargement when aided by the algorithm. • On a healthcare-screening cohort, our algorithm detected 71.0% (142/200) radiographs with moderate-to-severe left atrial enlargement while yielding 11.8% (492/4,184) false-positive rate.

To explore the optimum diameter threshold for solid nodules to define positive results at baseline screening low-dose CT (LDCT) and to compare two-dimensional and volumetric measurement of lung nodules for the diagnosis of lung cancers. We included consecutive participants from the Korean Lung Cancer Screening project between 2017 and 2018. The average transverse diameter and effective diameter (diameter of a sphere with the same volume) of lung nodules were measured by semi-automated segmentation. Diagnostic performances for lung cancers diagnosed within 1 year after LDCT were evaluated using area under receiver-operating characteristic curves (AUCs), sensitivities, and specificities, with diameter thresholds for solid nodules ranging from 6 to 10 mm. The reduction of unnecessary follow-up LDCTs and the diagnostic delay of lung cancers were estimated for each threshold. Fifty-two lung cancers were diagnosed among 10,424 (10,141 men; median age 62 years) participants within 1 year after LDCT. Average transverse (0.980) and effective diameters (0.981) showed similar AUCs (p = .739). Elevating the average transverse diameter threshold from 6 to 9 mm resulted in a significantly increased specificity (91.7 to 96.7%, p < .001), a modest reduction in sensitivity (96.2 to 94.2%, p = .317), a 60.2% estimated reduction of unnecessary follow-up LDCTs, and a diagnostic delay in 1.9% of lung cancers. Elevating the threshold to 10 mm led to a significant reduction in sensitivity (86.5%, p = .025). Elevating the diameter threshold for solid nodules from 6 to 9 mm may lead to a substantial reduction in unnecessary follow-up LDCTs with a small proportion of diagnostic delay of lung cancers. • Elevation of the diameter threshold for solid nodules from 6 to 9 mm can substantially reduce unnecessary follow-up LDCTs with a small proportion of diagnostic delay of lung cancers. • The average transverse and effective diameters of lung nodules showed similar performances for the prediction of a lung cancer diagnosis.

Background The performance of a deep learning algorithm for lung cancer detection on chest radiographs in a health screening population is unknown. Purpose To validate a commercially available deep learning algorithm for lung cancer detection on chest radiographs in a health screening population. Materials and Methods Out-of-sample testing of a deep learning algorithm was retrospectively performed using chest radiographs from individuals undergoing a comprehensive medical check-up between July 2008 and December 2008 (validation test). To evaluate the algorithm performance for visible lung cancer detection, the area under the receiver operating characteristic curve (AUC) and diagnostic measures, including sensitivity and false-positive rate (FPR), were calculated. The algorithm performance was compared with that of radiologists using the McNemar test and the Moskowitz method. Additionally, the deep learning algorithm was applied to a screening cohort undergoing chest radiography between January 2008 and December 2012, and its performances were calculated. Results In a validation test comprising 10 285 radiographs from 10 202 individuals (mean age, 54 years ± 11 [standard deviation]; 5857 men) with 10 radiographs of visible lung cancers, the algorithm's AUC was 0.99 (95% confidence interval: 0.97, 1), and it showed comparable sensitivity (90% [nine of 10 radiographs]) to that of the radiologists (60% [six of 10 radiographs]

To evaluate the degree of variability in computer-assisted interpretation of low-dose chest CTs (LDCTs) among radiologists in a nationwide lung cancer screening (LCS) program, through comparison with a retrospective interpretation from a central laboratory. Consecutive baseline LDCTs (n = 3353) from a nationwide LCS program were investigated. In the institutional reading, 20 radiologists in 14 institutions interpreted LDCTs using computer-aided detection and semi-automated segmentation systems for lung nodules. In the retrospective central review, a single radiologist re-interpreted all LDCTs using the same system, recording any non-calcified nodules ≥ 3 mm without arbitrary rejection of semi-automated segmentation to minimize the intervention of radiologist’s discretion. Positive results (requiring additional follow-up LDCTs or diagnostic procedures) were initially classified by the lung CT screening reporting and data system (Lung-RADS) during the interpretation, while the classifications based on the volumetric criteria from the Dutch-Belgian lung cancer screening trial (NELSON) were retrospectively applied. Variabilities in positive rates were assessed with coefficients of variation (CVs). In the institutional reading, positive rates by the Lung-RADS ranged from 7.5 to 43.3%, and those by the NELSON ranged from 11.4 to 45.0% across radiologists. The central review exhibited higher positive rates by Lung-RADS (20.0% vs. 27.3%; p

To develop and validate a preoperative CT-based deep learning model for the prediction of visceral pleural invasion (VPI) in early-stage lung cancer. In this retrospective study, dataset 1 (for training, tuning, and internal validation) included 676 patients with clinical stage IA lung adenocarcinomas resected between 2009 and 2015. Dataset 2 (for temporal validation) included 141 patients with clinical stage I adenocarcinomas resected between 2017 and 2018. A CT-based deep learning model was developed for the prediction of VPI and validated in terms of discrimination and calibration. An observer performance study and a multivariable regression analysis were performed. The area under the receiver operating characteristic curve (AUC) of the model was 0.75 (95% CI, 0.67–0.84), which was comparable to those of board-certified radiologists (AUC, 0.73–0.79; all p > 0.05). The model had a higher standardized partial AUC for a specificity range of 90 to 100% than the radiologists (all p 0.05), and its output was an independent predictor for VPI (adjusted odds ratio, 1.07; 95% CI, 1.03–1.11; p

Background Accurate detection of pneumothorax on chest radiographs, the most common complication of percutaneous transthoracic needle biopsies (PTNBs), is not always easy in practice. A computer-aided detection (CAD) system may help detect pneumothorax. Purpose To investigate whether a deep learning-based CAD system can improve detection performance for pneumothorax on chest radiographs after PTNB in clinical practice. Materials and Methods A CAD system for post-PTNB pneumothorax detection on chest radiographs was implemented in an institution in February 2020. This retrospective cohort study consecutively included chest radiographs interpreted with CAD assistance (CAD-applied group; February 2020 to November 2020) and those interpreted before implementation (non-CAD group; January 2018 to January 2020). The reference standard was defined by consensus reading by two radiologists. The diagnostic accuracy for pneumothorax was compared between the two groups using generalized estimating equations. Matching was performed according to whether the radiograph reader and PTNB operator were the same using the greedy method. Results A total of 676 radiographs from 655 patients (mean age: 67 years ± 11; 390 men) in the CAD-applied group and 676 radiographs from 664 patients (mean age: 66 years ± 12; 400 men) in the non-CAD group were included. The incidence of pneumothorax was 18.2% (123 of 676 radiographs) in the CAD-applied group and 22.5% (152 of 676 radiographs) in the non-CAD group (

RationaleThe World Health Organization (WHO) recommends systematic tuberculosis (TB) screening in prisons. Evidence is lacking for accurate and scalable screening approaches in this setting.ObjectivesTo assess the diagnostic accuracy of artificial intelligence-based chest x-ray interpretation algorithms for TB screening in prisons.MethodsProspective TB screening study in three prisons in Brazil from October 2017 to December 2019. We administered a standardized questionnaire, performed chest x-ray in a mobile unit, and collected sputum for confirmatory testing using Xpert MTB/RIF and culture. We evaluated x-ray images using three algorithms (CAD4TB version 6, LunitTB and qXR) and compared their diagnostic accuracy. We utilized multivariable logistic regression to assess the effect of demographic and clinical characteristics on algorithm accuracy. Finally, we investigated the relationship between abnormality scores and Xpert semi-quantitative results.Measurements and Main ResultsAmong 2,075 incarcerated individuals, 259 (12.5%) had confirmed TB. All three algorithms performed similarly overall with AUCs of 0.87-0.91. At 90% sensitivity, only LunitTB and qXR met the WHO Target Product Profile requirements for a triage test, with specificity of 84% and 74%, respectively. All algorithms had variable performance by age, prior TB, smoking, and presence of TB symptoms. LunitTB was the most robust to this heterogeneity, but nonetheless failed to meet the TPP for individuals with previous TB. Abnormality scores of all three algorithms were significantly correlated with sputum bacillary load.ConclusionsAutomated x-ray interpretation algorithms can be an effective triage tool for TB screening in prisons. However, their specificity is insufficient in individuals with previous TB.

We aimed to compare the CT interpretation before and after the implementation of a computerized system for lung nodule detection and measurements in a nationwide lung cancer screening program. Our screening program started in April 2017, with 14 participating institutions. Initially, all CTs were interpreted using interpretation systems in each institution and manual nodule measurement (conventional system). A cloud-based CT interpretation system, equipped with semi-automated measurement and CAD (computer-aided detection) for lung nodules (cloud-based system), was implemented during the project. Positive rates and performances for lung cancer diagnosis based on the Lung-RADS version 1.0 were compared between the conventional and cloud-based systems. A total of 1821 (M:F = 1782:39, mean age 62.7 years, 16 confirmed lung cancers) and 4666 participants (M:F = 4560:106, mean age 62.8 years, 31 confirmed lung cancers) were included in the conventional and cloud-based systems, respectively. Significantly more nodules were detected in the cloud-based system (0.76 vs. 1.07 nodule/participant, p

OBJECTIVE: To describe the experience of implementing a deep learning-based computer-aided detection (CAD) system for the interpretation of chest X-ray radiographs (CXR) of suspected coronavirus disease (COVID-19) patients and investigate the diagnostic performance of CXR interpretation with CAD assistance. MATERIALS AND METHODS: In this single-center retrospective study, initial CXR of patients with suspected or confirmed COVID-19 were investigated. A commercialized deep learning-based CAD system that can identify various abnormalities on CXR was implemented for the interpretation of CXR in daily practice. The diagnostic performance of radiologists with CAD assistance were evaluated based on two different reference standards: 1) real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) results for COVID-19 and 2) pulmonary abnormality suggesting pneumonia on chest CT. The turnaround times (TATs) of radiology reports for CXR and rRT-PCR results were also evaluated. RESULTS: Among 332 patients (male:female, 173:159; mean age, 57 years) with available rRT-PCR results, 16 patients (4.8%) were diagnosed with COVID-19. Using CXR, radiologists with CAD assistance identified rRT-PCR positive COVID-19 patients with sensitivity and specificity of 68.8% and 66.7%, respectively. Among 119 patients (male:female, 75:44; mean age, 69 years) with available chest CTs, radiologists assisted by CAD reported pneumonia on CXR with a sensitivity of 81.5% and a specificity of 72.3%. The TATs of CXR reports were significantly shorter than those of rRT-PCR results (median 51 vs. 507 minutes; p < 0.001). CONCLUSION: Radiologists with CAD assistance could identify patients with rRT-PCR-positive COVID-19 or pneumonia on CXR with a reasonably acceptable performance. In patients suspected with COVID-19, CXR had much faster TATs than rRT-PCRs.

Pneumothorax is the most common and potentially life-threatening complication arising from percutaneous lung biopsy. We evaluated the performance of a deep learning algorithm for detection of post-biopsy pneumothorax in chest radiographs (CRs), in consecutive cohorts reflecting actual clinical situation. We retrospectively included post-biopsy CRs of 1757 consecutive patients (1055 men, 702 women; mean age of 65.1 years) undergoing percutaneous lung biopsies from three institutions. A commercially available deep learning algorithm analyzed each CR to identify pneumothorax. We compared the performance of the algorithm with that of radiology reports made in the actual clinical practice. We also conducted a reader study, in which the performance of the algorithm was compared with those of four radiologists. Performances of the algorithm and radiologists were evaluated by area under receiver operating characteristic curves (AUROCs), sensitivity, and specificity, with reference standards defined by thoracic radiologists. Pneumothorax occurred in 17.5% (308/1757) of cases, out of which 16.6% (51/308) required catheter drainage. The AUROC, sensitivity, and specificity of the algorithm were 0.937, 70.5%, and 97.7%, respectively, for identification of pneumothorax. The algorithm exhibited higher sensitivity (70.2% vs. 55.5%, p

BACKGROUND AND OBJECTIVE: Deep learning (DL) algorithms have been developed for various tasks, including lung nodule detection on chest radiographs or lung cancer computed tomography screening, potential candidate selection in lung cancer screening, malignancy prediction for indeterminate pulmonary nodules, lung cancer staging, treatment response prediction, prognostication, and prediction of genetic mutations in lung cancer. Furthermore, these DL algorithms have been applied in various clinical settings in order for them to be generalized in real-world clinical practice. Multiple DL algorithms have been corroborated to be on par with experts or current clinical prediction models for several specific tasks. However, no article has yet comprehensively reviewed DL algorithms dedicated to lung cancer research. This narrative review presents an overview of the literature dealing with DL techniques applied in lung cancer research and briefly summarizes the results according to the DL algorithms’ clinical use cases. METHODS: we performed a narrative review by searching the Embase and OVID-MEDLINE databases for articles published in English from October, 2016 until September, 2021 and reviewing the bibliographies of key references to identify important literature related to DL in lung cancer research. The background, development, results, and clinical implications of each DL algorithm are briefly discussed. Lastly, we end this review article by highlighting future directions in lung cancer research using DL techniques. KEY CONTENT AND FINDINGS: DL algorithms have been introduced to show comparable or higher performance than human experts in various clinical settings. Specifically, they have been actively applied to detect lung nodules in chest radiographs or computed tomography (CT) examinations, optimize candidate selection for lung cancer screening (LCS), predict the malignancy of lung nodules, stage lung cancer, and predict treatment response, patients’ prognoses, and genetic mutations in lung cancers. CONCLUSIONS: DL algorithms have corroborated their potential value for various tasks, ranging from lung cancer screening to prognostication of lung cancer patients. Future research is warranted for the clinical application of these algorithms in daily clinical practice and verification of their real-world clinical usefulness.

To investigate the efficacy of an artificial intelligence (AI) system for the identification of false negatives in chest radiographs that were interpreted as normal by radiologists.We consecutively collected chest radiographs that were read as normal during 1 month (March 2020) in a single institution. A commercialized AI system was retrospectively applied to these radiographs. Radiographs with abnormal AI results were then re-interpreted by the radiologist who initially read the radiograph ("AI as the advisor" scenario). The reference standards for the true presence of relevant abnormalities in radiographs were defined by majority voting of three thoracic radiologists. The efficacy of the AI system was evaluated by detection yield (proportion of true-positive identification among the entire examination) and false-referral rate (FRR, proportion of false-positive identification among all examinations). Decision curve analyses were performed to evaluate the net benefits of applying the AI system.A total of 4208 radiographs from 3778 patients (M:F = 1542:2236; median age, 56 years) were included. The AI system identified initially overlooked relevant abnormalities with a detection yield and an FRR of 2.4% and 14.0%, respectively. In the "AI as the advisor" scenario, radiologists detected initially overlooked relevant abnormalities with a detection yield and FRR of 1.2% and 0.97%, respectively. In a decision curve analysis, AI as an advisor scenario exhibited a positive net benefit when the cost-to-benefit ratio was below 1:0.8.An AI system could identify relevant abnormalities overlooked by radiologists and could enable radiologists to correct their false-negative interpretations by providing feedback to radiologists.• In consecutive chest radiographs with normal interpretations, an artificial intelligence system could identify relevant abnormalities that were initially overlooked by radiologists. • The artificial intelligence system could enable radiologists to correct their initial false-negative interpretations by providing feedback to radiologists when overlooked abnormalities were present.

The long-term natural course and outcomes of subsolid nodules (SSNs) in terms of true growth, substantial growth, and stage shift need to be clarified.Between 2002 and 2016, 128 subjects with persistent SSNs of 3cm or smaller were enrolled. The baseline and interval changes in the series computed tomography (CT) findings during the follow-up period were subsequently reviewed.The mean follow-up period was 3.57±2.93years. The cumulative percentage of growth nodules of the part-solid nodule (PSN) group was significantly higher than that of the ground-glass nodule (GGN) group by Kaplan-Meier estimation (all p0.0001). For true SSN growth, GGNs usually take a median follow-up of 7 years to grow; PSNs usually take a median follow-up of 3 years to grow. For substantial SSN growth, GGNs usually take a median follow-up of 9 years to grow; PSNs usually take a median follow-up of 3 years to grow. For stage shift, GGNs usually take a median follow-up of 12 years to grow; PSNs usually take a median follow-up of 9 years to grow.The natural course in terms of true growth, substantial growth, and stage shift differed significantly according to their nodule type, which could contribute to the development of follow-up guidelines and management strategy of pulmonary SSNs.

Objective To evaluate quantitative magnetic resonance imaging (MRI) parameters for differentiation of cysts from and solid masses in the anterior mediastinum. Materials and Methods The development dataset included 18 patients from two institutions with pathologically-proven cysts (n = 6) and solid masses (n = 12) in the anterior mediastinum. We measured the maximum diameter, normalized T1 and T2 signal intensity (nT1 and nT2), normalized apparent diffusion coefficient (nADC), and relative enhancement ratio (RER) of each lesion. RERs were obtained by non-rigid registration and subtraction of precontrast and postcontrast T1-weighted images. Differentiation criteria between cysts and solid masses were identified based on receiver operating characteristics analysis. For validation, two separate datasets were utilized: 15 patients with 8 cysts and 7 solid masses from another institution (validation dataset 1); and 11 patients with clinically diagnosed cysts stable for more than two years (validation dataset 2). Sensitivity and specificity were calculated from the validation datasets. Results nT2, nADC, and RER significantly differed between cysts and solid masses (p = 0.032, 0.013, and < 0.001, respectively). The following criteria differentiated cysts from solid masses: RER < 26.1%; nADC > 0.63; nT2 > 0.39. In validation dataset 1, the sensitivity of the RER, nADC, and nT2 criteria was 87.5%, 100%, and 75.0%, and the specificity was 100%, 40.0%, and 57.4%, respectively. In validation dataset 2, the sensitivity of the RER, nADC, and nT2 criteria was 90.9%, 90.9%, and 72.7%, respectively. Conclusion Quantitative MRI criteria using nT2, nADC, and particularly RER can assist differentiation of cysts from solid masses in the anterior mediastinum.

Background Detection of active pulmonary tuberculosis on chest radiographs (CRs) is critical for the diagnosis and screening of tuberculosis. An automated system may help streamline the tuberculosis screening process and improve diagnostic performance. Methods We developed a deep learning–based automatic detection (DLAD) algorithm using 54c221 normal CRs and 6768 CRs with active pulmonary tuberculosis that were labeled and annotated by 13 board-certified radiologists. The performance of DLAD was validated using 6 external multicenter, multinational datasets. To compare the performances of DLAD with physicians, an observer performance test was conducted by 15 physicians including nonradiology physicians, board-certified radiologists, and thoracic radiologists. Image-wise classification and lesion-wise localization performances were measured using area under the receiver operating characteristic (ROC) curves and area under the alternative free-response ROC curves, respectively. Sensitivities and specificities of DLAD were calculated using 2 cutoffs (high sensitivity [98%] and high specificity [98%]) obtained through in-house validation. Results DLAD demonstrated classification performance of 0.977–1.000 and localization performance of 0.973–1.000. Sensitivities and specificities for classification were 94.3%–100% and 91.1%–100% using the high-sensitivity cutoff and 84.1%–99.0% and 99.1%–100% using the high-specificity cutoff. DLAD showed significantly higher performance in both classification (0.993 vs 0.746–0.971) and localization (0.993 vs 0.664–0.925) compared to all groups of physicians. Conclusions Our DLAD demonstrated excellent and consistent performance in the detection of active pulmonary tuberculosis on CR, outperforming physicians, including thoracic radiologists., A deep learning–based algorithm outperformed radiologists in detecting active pulmonary tuberculosis on chest radiographs and thus may play an important role in diagnosis and screening of tuberculosis in select situations, contributing to the reduction of the high burden of tuberculosis worldwide.

To investigate the incidence of thoracic recurrence and the diagnostic value of chest CT for postoperative surveillance in curatively-resected colorectal cancer (CRC) patients. This retrospective study consisted of 648 CRC patients (M:F, 393:255; mean age, 66.2 years) treated with curative surgery between January 2010 and December 2012. The presence of CRC recurrence over follow-ups was analysed and recurrence-free survival and risk factors of recurrence were assessed using Kaplan–Meier analysis with log-rank test and Cox-regression analysis, respectively. Over a median follow-up of 57 months, thoracic recurrence occurred in 8.0% (52/648) of patients with a median recurrence-free survival rate of 19.5 months. Among the 52 patients with thoracic recurrence, 18 (2.7%) had isolated thoracic recurrence, and only five (0.8%) were diagnosed through chest CT. Risk factors of overall thoracic recurrence included age, positive resection margin, presence of venous invasion, positive pathologic N-class, and presence of abdominal recurrence (odds ratio [OR] = 1.78, 19.691, 2.993, 2.502, and 31.137; p = 0.045, 0.004, 0.001, 0.005, and p < 0.001, respectively). As for isolated thoracic recurrence, serum carcinoembryonic antigen level ≥ 5 ng/mL during postoperative follow-up (OR = 9.112; p < 0.001) was demonstrated to be the only predictive factor. There were no thoracic recurrences in patients with CRC stages 0 and I. In patients with curatively-resected CRCs, routine surveillance using chest CT may be of limited value, particularly in those with CRC stages 0 or I, as recurrence only detectable through chest CT was shown to be rare. • Postoperative thoracic recurrence only detectable through chest CT was shown to be rare. • There were no thoracic recurrences in colorectal cancers stage 0 and I. • Postoperative surveillance chest CT is of limited value in patients with curatively resected colorectal cancers.

Chest X-rays (CXRs) can help triage for Coronavirus disease (COVID-19) patients in resource-constrained environments, and a computer-aided detection system (CAD) that can identify pneumonia on CXR may help the triage of patients in those environment where expert radiologists are not available. However, the performance of existing CAD for identifying COVID-19 and associated pneumonia on CXRs has been scarcely investigated. In this study, CXRs of patients with and without COVID-19 confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) were retrospectively collected from four and one institution, respectively, and a commercialized, regulatory-approved CAD that can identify various abnormalities including pneumonia was used to analyze each CXR. Performance of the CAD was evaluated using area under the receiver operating characteristic curves (AUCs), with reference standards of the RT-PCR results and the presence of findings of pneumonia on chest CTs obtained within 24 hours from the CXR. For comparison, 5 thoracic radiologists and 5 non-radiologist physicians independently interpreted the CXRs. Afterward, they re-interpreted the CXRs with corresponding CAD results. The performance of CAD (AUCs, 0.714 and 0.790 against RT-PCR and chest CT, respectively hereinafter) were similar with those of thoracic radiologists (AUCs, 0.701 and 0.784), and higher than those of non-radiologist physicians (AUCs, 0.584 and 0.650). Non-radiologist physicians showed significantly improved performance when assisted with the CAD (AUCs, 0.584 to 0.664 and 0.650 to 0.738). In addition, inter-reader agreement among physicians was also improved in the CAD-assisted interpretation (Fleiss’ kappa coefficient, 0.209 to 0.322). In conclusion, radiologist-level performance of the CAD in identifying COVID-19 and associated pneumonia on CXR and enhanced performance of non-radiologist physicians with the CAD assistance suggest that the CAD can support physicians in interpreting CXRs and helping image-based triage of COVID-19 patients in resource-constrained environment.

To study the extent of pulmonary involvement in coronavirus 19 (COVID-19) with quantitative CT and to assess the impact of disease burden on opacity visibility on chest radiographs.This retrospective study included 20 pairs of CT scans and same-day chest radiographs from 17 patients with COVID-19, along with 20 chest radiographs of controls. All pulmonary opacities were semiautomatically segmented on CT images, producing an anteroposterior projection image to match the corresponding frontal chest radiograph. The quantitative CT lung opacification mass (QCTThe mean QCTQCT

PURPOSE: To evaluate the performance of a deep learning–based algorithm in detecting lung cancers not reported on posteroanterior chest radiographs during routine practice. MATERIALS AND METHODS: The retrospective test dataset included 168 posteroanterior chest radiographs acquired between March 2017 and December 2018 (168 patients; mean age, 71.9 years ± 9.5 [standard deviation]; age range, 42–91 years) with 187 lung cancers (mean size, 2.3 cm ± 1.2) undetected during initial clinical evaluation, and 50 normal chest radiographs. CT served as the reference standard for ground truth. Four thoracic radiologists independently reevaluated the chest radiographs for lung nodules both without and with the aid of the algorithm. The performances of the algorithm and the radiologists were evaluated and compared on a per–chest radiograph basis and a per-lesion basis, according to the area under the receiver operating characteristic curve (AUROC) and area under the jackknife free-response ROC curve (AUFROC). RESULTS: The algorithm showed excellent diagnostic performances both in terms of per-chest radiograph classification (AUROC, 0.899) and per-lesion localization (AUFROC, 0.744); both of these values were significantly higher than those of the radiologists (AUROC, 0.634–0.663; AUFROC, 0.619–0.651; P < .001 for all). The algorithm also demonstrated higher sensitivity (69.6% [117 of 168] vs 47.0% [316 of 672]; P < .001) and specificity (94.0% [47 of 50] vs 78.0% [156 of 200]; P = .01). When assisted by the algorithm, the radiologists’ AUROC (0.634–0.663 vs 0.685–0.724; P < 0.01 for all) and pooled AUFROC (0.636 vs 0.688; P = .03) substantially improved. The false-positive rate of the algorithm, that is, the total number of false-positive nodules divided by the total number of chest radiographs, was similar to that of pooled radiologists (21.1% [46 of 218] vs 19.0% [166 of 872]; P > .05). CONCLUSION: A deep learning–based nodule detection algorithm showed excellent detection performance of lung cancers that were not reported on chest radiographs during routine practice and significantly reduced reading errors when used as a second reader. Supplemental material is available for this article. © RSNA, 2020 See also commentary by White in this issue.

Background The presence of cavities is associated with unfavorable prognosis in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, little is known about the characteristics of such cavities and their impact on clinical outcomes. The aim of this study was to investigate the size of cavities and their implications on treatment outcomes and mortality in patients with NTM-PD. Methods We included patients diagnosed with NTM-PD at Seoul National University Hospital between January 1, 2007, and December 31, 2018. We measured the size of cavities on chest computed tomography scans performed at the time of diagnosis and used multivariable logistic regression and Cox proportional hazards regression analysis to investigate the impact of these measurements on treatment outcomes and mortality. Results The study cohort comprised 421 patients (noncavitary, n = 329; cavitary, n = 92) with NTM-PD. During a median follow-up period of 49 months, 118 (35.9%) of the 329 patients with noncavitary and 64 (69.6%) of the 92 patients with cavitary NTM-PD received antibiotic treatment. Cavities >2 cm were associated with worse treatment outcomes (adjusted odds ratio, 0.41; 95% CI, 0.17–0.96) and higher mortality (adjusted hazard ratio, 2.52; 95% CI, 1.09–5.84), while there was no difference in treatment outcomes or mortality between patients with cavities ≤2 cm and patients with noncavitary NTM-PD. Conclusions Clinical outcomes are different according to the size of cavities in patients with cavitary NTM-PD; thus, the measurement of the size of cavities could help in making clinical decisions.

To develop deep learning-based cardiac chamber enlargement-detection algorithms for left atrial (DLCE-LAE) and ventricular enlargement (DLCE-LVE), on chest radiographs METHODS: For training and internal validation of DLCE-LAE and -LVE, 5,045 chest radiographs (CRs; 2,463 normal and 2,393 LAE) and 1,012 CRs (456 normal and 456 LVE) matched with the same-day echocardiography were collected, respectively. External validation was performed using 107 temporally independent CRs. Reader performance test was conducted using the external validation dataset by five cardiothoracic radiologists without and with the results of DLCE. Classification performance of DLCE was evaluated and compared with those of the readers and conventional radiographic features, including cardiothoracic ratio, carinal angle, and double contour. In addition, DLCE-LAE was tested on 5,277 CRs from a healthcare screening program cohort.DLCE-LAE showed areas under the receiver operating characteristics curve (AUROCs) of 0.858 on external validation. On reader performance test, DLCE-LAE showed better results than pooled radiologists (AUROC 0.858 vs. 0.651; p.001) and significantly increased their performance when used as a second reader (AUROC 0.651 vs. 0.722; p.001). DLCE-LAE also showed a significantly higher AUROC than conventional radiographic findings (AUROC 0.858 vs. 0.535-0.706; all ps.01). In the healthcare screening cohort, DLCE-LAE successfully detected 71.0% (142/200) CRs with moderate-to-severe LAE (93.5% [29/31] of severe cases), while yielding 11.8% (492/4,184) false-positive rate. DLCE-LVE showed AUROCs of 0.966 and 0.594 on internal and external validation, respectively.DLCE-LAE outperformed and improved cardiothoracic radiologists' performance in detecting LAE and showed promise in screening individuals with moderate-to-severe LAE in a healthcare screening cohort.• Our deep learning algorithm outperformed cardiothoracic radiologists in detecting left atrial enlargement on chest radiographs. • Cardiothoracic radiologists improved their performance in detecting left atrial enlargement when aided by the algorithm. • On a healthcare-screening cohort, our algorithm detected 71.0% (142/200) radiographs with moderate-to-severe left atrial enlargement while yielding 11.8% (492/4,184) false-positive rate.

To explore the optimum diameter threshold for solid nodules to define positive results at baseline screening low-dose CT (LDCT) and to compare two-dimensional and volumetric measurement of lung nodules for the diagnosis of lung cancers.We included consecutive participants from the Korean Lung Cancer Screening project between 2017 and 2018. The average transverse diameter and effective diameter (diameter of a sphere with the same volume) of lung nodules were measured by semi-automated segmentation. Diagnostic performances for lung cancers diagnosed within 1 year after LDCT were evaluated using area under receiver-operating characteristic curves (AUCs), sensitivities, and specificities, with diameter thresholds for solid nodules ranging from 6 to 10 mm. The reduction of unnecessary follow-up LDCTs and the diagnostic delay of lung cancers were estimated for each threshold.Fifty-two lung cancers were diagnosed among 10,424 (10,141 men; median age 62 years) participants within 1 year after LDCT. Average transverse (0.980) and effective diameters (0.981) showed similar AUCs (p = .739). Elevating the average transverse diameter threshold from 6 to 9 mm resulted in a significantly increased specificity (91.7 to 96.7%, p.001), a modest reduction in sensitivity (96.2 to 94.2%, p = .317), a 60.2% estimated reduction of unnecessary follow-up LDCTs, and a diagnostic delay in 1.9% of lung cancers. Elevating the threshold to 10 mm led to a significant reduction in sensitivity (86.5%, p = .025).Elevating the diameter threshold for solid nodules from 6 to 9 mm may lead to a substantial reduction in unnecessary follow-up LDCTs with a small proportion of diagnostic delay of lung cancers.• Elevation of the diameter threshold for solid nodules from 6 to 9 mm can substantially reduce unnecessary follow-up LDCTs with a small proportion of diagnostic delay of lung cancers. • The average transverse and effective diameters of lung nodules showed similar performances for the prediction of a lung cancer diagnosis.

To develop and validate a preoperative CT-based deep learning model for the prediction of visceral pleural invasion (VPI) in early-stage lung cancer.In this retrospective study, dataset 1 (for training, tuning, and internal validation) included 676 patients with clinical stage IA lung adenocarcinomas resected between 2009 and 2015. Dataset 2 (for temporal validation) included 141 patients with clinical stage I adenocarcinomas resected between 2017 and 2018. A CT-based deep learning model was developed for the prediction of VPI and validated in terms of discrimination and calibration. An observer performance study and a multivariable regression analysis were performed.The area under the receiver operating characteristic curve (AUC) of the model was 0.75 (95% CI, 0.67-0.84), which was comparable to those of board-certified radiologists (AUC, 0.73-0.79; all p 0.05). The model had a higher standardized partial AUC for a specificity range of 90 to 100% than the radiologists (all p 0.05). The high sensitivity cutoff (0.245) yielded a sensitivity of 93.8% and a specificity of 31.2%, and the high specificity cutoff (0.448) resulted in a sensitivity of 47.9% and a specificity of 86.0%. Two of the three radiologists provided highly sensitive (93.8% and 97.9%) but not specific (48.4% and 40.9%) diagnoses. The model showed good calibration (p 0.05), and its output was an independent predictor for VPI (adjusted odds ratio, 1.07; 95% CI, 1.03-1.11; p 0.001).The deep learning model demonstrated a radiologist-level performance. The model could achieve either highly sensitive or highly specific diagnoses depending on clinical needs.• The preoperative CT-based deep learning model demonstrated an expert-level diagnostic performance for the presence of visceral pleural invasion in early-stage lung cancer. • Radiologists had a tendency toward highly sensitive, but not specific diagnoses for the visceral pleural invasion.

Purpose Meteorin-like protein (METRNL) (also known as IL-41), recently identified as a myokine, is released in response to muscle contraction. It improves the skeletal muscle insulin sensitivity through exerting a beneficial anti-inflammatory effect. However, no independent studies have been published to verify the effects of METRNL on human umbilical vein endothelial cells (HUVECs) and THP-1 human monocytes. Materials and methods The levels of NFκB and IκB phosphorylation as well as the expression of adhesion molecules were assessed by Western blotting analysis. Cell adhesion assay demonstrated the interactions between HUVEC and THP-1 ​cells. We used enzyme-linked immunosorbent assay (ELISA) to measure the levels of TNFα and MCP-1 in culture medium. Results Treatment with METRNL suppressed the secretion of TNFα and MCP-1 as well as NFκB and IκB phosphorylation and inflammatory markers in lipopolysaccharide (LPS)-treated HUVECs and THP-1 ​cells. Furthermore, treatment with METRNL ameliorated LPS-induced attachment of THP-1 monocytes to HUVECs via inhibition of adhesion molecule expression and apoptosis. Treatment of HUVEC and THP-1 ​cells with METRNL enhanced AMPK phosphorylation and PPARδ expression in a dose-dependent manner. Small interference (si) RNA-mediated suppression of AMPK or PPARδ restored all these changes. Conclusions It has therefore been shown that METRNL ameliorates inflammatory responses through AMPK and PPARδ-dependent pathways in LPS-treated HUVEC. In sum, the current study may suggest the suppressive potential of METRNL against endothelial inflammation.

To evaluate the degree of variability in computer-assisted interpretation of low-dose chest CTs (LDCTs) among radiologists in a nationwide lung cancer screening (LCS) program, through comparison with a retrospective interpretation from a central laboratory.Consecutive baseline LDCTs (n = 3353) from a nationwide LCS program were investigated. In the institutional reading, 20 radiologists in 14 institutions interpreted LDCTs using computer-aided detection and semi-automated segmentation systems for lung nodules. In the retrospective central review, a single radiologist re-interpreted all LDCTs using the same system, recording any non-calcified nodules ≥ 3 mm without arbitrary rejection of semi-automated segmentation to minimize the intervention of radiologist's discretion. Positive results (requiring additional follow-up LDCTs or diagnostic procedures) were initially classified by the lung CT screening reporting and data system (Lung-RADS) during the interpretation, while the classifications based on the volumetric criteria from the Dutch-Belgian lung cancer screening trial (NELSON) were retrospectively applied. Variabilities in positive rates were assessed with coefficients of variation (CVs).In the institutional reading, positive rates by the Lung-RADS ranged from 7.5 to 43.3%, and those by the NELSON ranged from 11.4 to 45.0% across radiologists. The central review exhibited higher positive rates by Lung-RADS (20.0% vs. 27.3%; p .001) and the NELSON (23.1% vs. 37.0%; p .001), and lower inter-institution variability (CV, 0.30 vs. 0.12, p = .003 by Lung-RADS; CV, 0.25 vs. 0.12, p = .014 by the NELSON) compared to the institutional reading.Considerable inter-institution variability in the interpretation of LCS results is caused by different usage of the computer-assisted system.• Considerable variability existed in the interpretation of screening LDCT among radiologists partly from the different usage of the computerized system. • A retrospective reading of low-dose chest CTs in the central laboratory resulted in reduced variability but an increased positive rate.

We aimed to compare the CT interpretation before and after the implementation of a computerized system for lung nodule detection and measurements in a nationwide lung cancer screening program.Our screening program started in April 2017, with 14 participating institutions. Initially, all CTs were interpreted using interpretation systems in each institution and manual nodule measurement (conventional system). A cloud-based CT interpretation system, equipped with semi-automated measurement and CAD (computer-aided detection) for lung nodules (cloud-based system), was implemented during the project. Positive rates and performances for lung cancer diagnosis based on the Lung-RADS version 1.0 were compared between the conventional and cloud-based systems.A total of 1821 (M:F = 1782:39, mean age 62.7 years, 16 confirmed lung cancers) and 4666 participants (M:F = 4560:106, mean age 62.8 years, 31 confirmed lung cancers) were included in the conventional and cloud-based systems, respectively. Significantly more nodules were detected in the cloud-based system (0.76 vs. 1.07 nodule/participant, p .001). Positive rate did not differ significantly between the two systems (9.9% vs. 11.0%, p = .211), while their variability across institutions was significantly lower in the cloud-based system (coefficients of variability, 0.519 vs. 0.311, p = .018). The Lung-RADS-based sensitivity (93.8% vs. 93.5%, p = .979) and specificity (90.9% vs. 89.6%, p = .132) did not differ significantly between the two systems.Implementation of CAD and semi-automated measurement for lung nodules in a nationwide lung cancer screening program resulted in increased number of detected nodules and reduced variability in positive rates across institutions.• Computer-aided CT reading detected more lung nodules than radiologists alone in lung cancer screening. • Positive rate in lung cancer screening did not change with computer-aided reading. • Computer-aided CT reading reduced inter-institutional variability in lung cancer screening.

Background It remains unclear whether 5 years of stability is sufficient to establish the benign behavior of subsolid nodules (SSNs) of the lung. There are no guidelines for the length of follow-up needed for these SSNs. Purpose To investigate the incidence of interval growth of pulmonary SSNs 6 mm or greater in diameter after 5 years of stability and their clinical outcome. Materials and Methods This retrospective study assessed SSNs 6 mm or greater that were stable for 5 years after detection (January 2002 to December 2018). The incidence of interval growth after 5 years of stability and the clinical and radiologic features of these SSNs were investigated. Clinical stage shifts of growing SSNs, presence of metastasis, and overall survival were assessed during the follow-up period. Subgroup analysis was performed in patients with nonenhanced thin-section (section thickness ≤1.5 mm) CT for interval growth after 5 years of stability. Results A total of 235 SSNs in 235 patients (mean age, 64 years ± 10 [standard deviation]; 132 women) were evaluated. There were 212 pure ground-glass nodules and 24 part-solid nodules. During follow-up (median, 112 months; range, 84-208 months), five of the 235 SSNs (2%; three primary ground-glass nodules and two part-solid nodules) showed interval growth. Three of these five growing SSNs were 10 mm or greater. Three of the five SSNs with interval growth had clinical stage shifts after growth (from Tis [in situ] to T1mi [minimally invasive] in one lesion; from T1mi to T1a in two lesions). There were no deaths or metastases from lung cancer during follow-up. Of 160 SSNs imaged with section thickness of 1.5 mm or less, two (1%) grew; both lesions were 10 mm or greater. Conclusion Only 2% of subsolid pulmonary nodules greater than or equal to 6 mm that had been stable for 5 years showed subsequent growth. At median follow-up of 9 years (after the initial 5-year period of stability), growth of those lung nodules had no clinical effect. © RSNA, 2020 See also the editorial by Naidich and Azour in this issue.