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Contains fulltext : 235584.pdf (Publisher’s version ) (Open Access) Lung cancer computed tomography (CT) screening trials using low-dose CT have repeatedly demonstrated a reduction in the number of lung cancer deaths in the screening group compared to a control group. With various countries currently considering the implementation of lung cancer screening, recurring discussion points are, among others, the potentially high false positive rates, cost-effectiveness, and the availability of radiologists for scan interpretation. Artificial intelligence (AI) has the potential to increase the efficiency of lung cancer screening. We discuss the performance levels of AI algorithms for various tasks related to the interpretation of lung screening CT scans, how they compare to human experts, and how AI and humans may complement each other. We discuss how AI may be used in the lung cancer CT screening workflow according to the current evidence and describe the additional research that will be required before AI can take a more prominent role in the analysis of lung screening CT scans.

In this study, we investigate the detection of cardiomegaly on frontal chest radiographs through two alternative deep-learning approaches - via anatomical segmentation and via image-level classification. We used the publicly available ChestX-ray14 dataset, and obtained heart and lung segmentation annotations for 778 chest radiographs for the development of the segmentation-based approach. The classification-based method was trained with 65k standard chest radiographs with image-level labels. For both approaches, the best models were found through hyperparameter searches where architectural, learning, and regularization related parameters were optimized systematically. The resulting models were tested on a set of 367 held-out images for which cardiomegaly annotations were hand-labeled by two independent expert radiologists. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated. The performance of the segmentation-based system with an AUC of 0.977 is significantly better for classifying cardiomegaly than the classification-based model which achieved an AUC of 0.941. Only the segmentation-based model achieved comparable performance to an independent expert reader (AUC of 0.978). We conclude that the segmentation-based model requires 100 times fewer annotated chest radiographs to achieve a substantially better performance, while also producing more interpretable results.

We propose a deep learning system to automatically detect four explainable emphysema signs on frontal and lateral chest radiographs. Frontal and lateral chest radiographs from 3000 studies were retrospectively collected. Two radiologists annotated these with 4 radiological signs of pulmonary emphysema identified from the literature. A patient with ≥2 of these signs present is considered emphysema positive. Using separate deep learning systems for frontal and lateral images we predict the presence of each of the four visual signs and use these to determine emphysema positivity. The ROC and AUC results on a set of 422 held-out cases, labeled by both radiologists, are reported. Comparison with a black-box model which predicts emphysema without the use of explainable visual features is made on the annotations from both radiologists, as well as the subset that they agreed on. DeLong’s test is used to compare with the black-box model ROC and McNemar’s test to compare with radiologist performance. In 422 test cases, emphysema positivity was predicted with AUCs of 0.924 and 0.946 using the reference standard from each radiologist separately. Setting model sensitivity equivalent to that of the second radiologist, our model has a comparable specificity (p= 0.880 andp= 0.143 for each radiologist respectively). Our method is comparable with the black-box model with AUCs of 0.915 (p= 0.407) and 0.935 (p= 0.291), respectively. On the 370 cases where both radiologists agreed (53 positives), our model achieves an AUC of 0.981, again comparable to the black-box model AUC of 0.972 (p= 0.289). Our proposed method can predict emphysema positivity on chest radiographs as well as a radiologist or a comparable black-box method. It additionally produces labels for four visual signs to ensure the explainability of the result. The dataset is publicly available athttps://doi.org/10.5281/zenodo.6373392.

Contains fulltext : 238628.pdf (Publisher’s version ) (Closed access) Purpose: To compare the performance of a convolutional neural network (CNN) to that of 11 radiologists in detecting scaphoid bone fractures on conventional radiographs of the hand, wrist, and scaphoid. Materials and Methods: At two hospitals (hospitals A and B), three datasets consisting of conventional hand, wrist, and scaphoid radiographs were retrospectively retrieved: a dataset of 1039 radiographs (775 patients [mean age, 48 years +/- 23 {standard deviation}; 505 female patients], period: 2017-2019, hospitals A and B) for developing a scaphoid segmentation CNN, a dataset of 3000 radiographs (1846 patients [mean age, 42 years +/- 22; 937 female patients], period: 2003-2019, hospital B) for developing a scaphoid fracture detection CNN, and a dataset of 190 radiographs (190 patients [mean age, 43 years +/- 20; 77 female patients], period: 2011-2020, hospital A) for testing the complete fracture detection system. Both CNNs were applied consecutively: The segmentation CNN localized the scaphoid and then passed the relevant region to the detection CNN for fracture detection. In an observer study, the performance of the system was compared with that of 11 radiologists. Evaluation metrics included the Dice similarity coefficient (DSC), Hausdorff distance (HD), sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Results: The segmentation CNN achieved a DSC of 97.4% +/- 1.4 with an HD of 1.31 mm +/- 1.03. The detection CNN had sensitivity of 78% (95% CI: 70, 86), specificity of 84% (95% CI: 77, 92), PPV of 83% (95% CI: 77, 90), and AUC of 0.87 (95% CI: 0.81, 0.91). There was no difference between the AUC of the CNN and that of the radiologists (0.87 [95% CI: 0.81, 0.91] vs 0.83 [radiologist range: 0.79-0.85]; P = .09). Conclusion: The developed CNN achieved radiologist-level performance in detecting scaphoid bone fractures on conventional radiographs of the hand, wrist, and scaphoid.Keywords: Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms, Feature Detection-Vision-Application Domain, Computer-Aided DiagnosisSee also the commentary by Li and Torriani in this issue.Supplemental material is available for this article.(c)RSNA, 2021.

Contains fulltext : 229492.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To compare nodule enhancement on subtraction CT iodine maps to that on dual-energy CT iodine maps using CT datasets acquired simultaneously. METHODS: A previously-acquired set of lung subtraction and dual-energy CT maps consisting of thirty patients with 95solid pulmonary nodules (>/=4mm diameter) was used. Nodules were annotated and segmented on CT angiography, and mean nodule enhancement in the iodine maps calculated. Three radiologists scored nodule visibility with both techniques on a 4-point scale. RESULTS: Mean nodule enhancement was higher (p

Background: Accurate estimation of the malignancy risk of pulmonary nodules at chest CT is crucial for optimizing management in lung cancer screening. Purpose: To develop and validate a deep learning (DL) algorithm for malignancy risk estimation of pulmonary nodules detected at screening CT. Materials and Methods: In this retrospective study, the DL algorithm was developed with 16 077 nodules (1249 malignant) collected between 2002 and 2004 from the National Lung Screening Trial. External validation was performed in the following three cohorts collected between 2004 and 2010 from the Danish Lung Cancer Screening Trial: a full cohort containing all 883 nodules (65 malignant) and two cancer-enriched cohorts with size matching (175 nodules, 59 malignant) and without size matching (177 nodules, 59 malignant) of benign nodules selected at random. Algorithm performance was measured by using the area under the receiver operating characteristic curve (AUC) and compared with that of the Pan-Canadian Early Detection of Lung Cancer (PanCan) model in the full cohort and a group of 11 clinicians composed of four thoracic radiologists, five radiology residents, and two pulmonologists in the cancer-enriched cohorts. Results: The DL algorithm significantly outperformed the PanCan model in the full cohort (AUC, 0.93 [95% CI: 0.89, 0.96] vs 0.90 [95% CI: 0.86, 0.93]; P = .046). The algorithm performed comparably to thoracic radiologists in cancer-enriched cohorts with both random benign nodules (AUC, 0.96 [95% CI: 0.93, 0.99] vs 0.90 [95% CI: 0.81, 0.98]; P = .11) and size-matched benign nodules (AUC, 0.86 [95% CI: 0.80, 0.91] vs 0.82 [95% CI: 0.74, 0.89]; P = .26). Conclusion: The deep learning algorithm showed excellent performance, comparable to thoracic radiologists, for malignancy risk estimation of pulmonary nodules detected at screening CT. This algorithm has the potential to provide reliable and reproducible malignancy risk scores for clinicians, which may help optimize management in lung cancer screening.

An observer study showed that two of the three top-performing algorithms from a public competition (Kaggle Data Science Bowl 2017) attained performances that were not significantly worse than that of 11 radiologists for estimating lung cancer risk on low-dose CT scans. Purpose. To determine whether deep learning algorithms developed in a public competition could identify lung cancer on low-dose CT scans with a performance similar to that of radiologists. Materials and Methods. In this retrospective study, a dataset consisting of 300 patient scans was used for model assessment; 150 patient scans were from the competition set and 150 were from an independent dataset. Both test datasets contained 50 cancer-positive scans and 100 cancer-negative scans. The reference standard was set by histopathologic examination for cancer-positive scans and imaging follow-up for at least 2 years for cancer-negative scans. The test datasets were applied to the three top-performing algorithms from the Kaggle Data Science Bowl 2017 public competition: grt123, Julian de Wit and Daniel Hammack (JWDH), and Aidence. Model outputs were compared with an observer study of 11 radiologists that assessed the same test datasets. Each scan was scored on a continuous scale by both the deep learning algorithms and the radiologists. Performance was measured using multireader, multicase receiver operating characteristic analysis. Results. The area under the receiver operating characteristic curve (AUC) was 0.877 (95% CI: 0.842, 0.910) for grt123, 0.902 (95% CI: 0.871, 0.932) for JWDH, and 0.900 (95% CI: 0.870, 0.928) for Aidence. The average AUC of the radiologists was 0.917 (95% CI: 0.889, 0.945), which was significantly higher than grt123 (P = .02); however, no significant difference was found between the radiologists and JWDH (P = .29) or Aidence (P = .26). Conclusion. Deep learning algorithms developed in a public competition for lung cancer detection in low-dose CT scans reached performance close to that of radiologists.

Background The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed. Purpose To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems. Materials and Methods The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted κ values, and classification accuracy. Results A total of 105 patients (mean age, 62 years ± 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years ± 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted κ values of 0.60 ± 0.01 for CO-RADS scores and 0.54 ± 0.01 for CT severity scores. Conclusion With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. © RSNA, 2020 Supplemental material is available for this article.

Simple Summary The risk assessment of pulmonary nodules on chest computed tomography (CT) is key to the early detection of lung cancer. Whereas a nodule’s morphological characteristics are strong predictors of malignancy for that individual nodule, it remains unclear whether the frequency and CT features of pulmonary nodules contribute to the prediction accuracy of future development of LC in another location. This was found by performing risk prediction modelling using age, sex, and CT measures from lung-cancer-free scans as predictors. We found that a greater number of part-solid and ground-glass nodules in the earliest scan was linearly associated with a higher risk of lung cancer developing in another location in the future. There were also indications that CT biomarkers of other pulmonary and heart diseases are risk factors for lung cancer. Our findings endorse the utilization of information from the entire scan to improve the accuracy of lung risk assessment. Abstract The purpose of this case–cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.

An observer study with seven radiologists showed that using a dedicated CT lung screening viewer (with computer-aided detection, a segmentation algorithm, and automatic Lung Imaging Reporting and Data System [Lung-RADS] categorization) improved interobserver agreement for Lung-RADS categorization while substantially reducing the reading time. Purpose. To compare the inter- and intraobserver agreement and reading times achieved when assigning Lung Imaging Reporting and Data System (Lung-RADS) categories to baseline and follow-up lung cancer screening studies by using a dedicated CT lung screening viewer with integrated nodule detection and volumetric support with those achieved by using a standard picture archiving and communication system (PACS)-like viewer. Materials and Methods. Data were obtained from the National Lung Screening Trial (NLST). By using data recorded by NLST radiologists, scans were assigned to Lung-RADS categories. For each Lung-RADS category (1 or 2, 3, 4A, and 4B), 40 CT scans (20 baseline scans and 20 follow-up scans) were randomly selected for 160 participants (median age, 61 years; interquartile range, 58-66 years; 61 women) in total. Seven blinded observers independently read all CT scans twice in a randomized order with a 2-week washout period: once by using the standard PACS-like viewer and once by using the dedicated viewer. Observers were asked to assign a Lung-RADS category to each scan and indicate the risk-dominant nodule. Inter- and intraobserver agreement was analyzed by using Fleiss k values and Cohen weighted k values, respectively. Reading times were compared by using a Wilcoxon signed rank test. Results. The interobserver agreement was moderate for the standard viewer and substantial for the dedicated viewer, with Fleiss k values of 0.58 (95% CI: 0.55, 0.60) and 0.66 (95% CI: 0.64, 0.68), respectively. The intraobserver agreement was substantial, with a mean Cohen weighted k value of 0.67. The median reading time was significantly reduced from 160 seconds with the standard viewer to 86 seconds with the dedicated viewer (P < .001). Conclusion. Lung-RADS interobserver agreement increased from moderate to substantial when using the dedicated CT lung screening viewer. The median reading time was substantially reduced when scans were read by using the dedicated CT lung screening viewer.

Contains fulltext : 229529.pdf (Publisher’s version ) (Open Access) Several studies investigated the appearance of intrapulmonary lymph nodes (IPLNs) at CT with pathologic correlation. IPLNs are benign lesions and do not require follow-up after initial detection. There are indications that IPLNs represent a considerable portion of incidentally found pulmonary nodules seen at high-resolution CT. The reliable and accurate identification of IPLNs as benign nodules may substantially reduce the number of unnecessary follow-up CT examinations. Typical CT features of IPLNs are a noncalcified solid nodule with sharp margins; a round, oval, or polygonal shape; distanced 15 mm or less from the pleura; and most being located below the level of the carina. The term perifissural nodule (PFN) was coined based on some of these characteristics. Standardization of those CT criteria are a prerequisite for accurate nodule classification. However, four different definitions of PFNs can currently be found in the literature. Furthermore, there is considerable variation in the reported interobserver agreement, malignancy rate, and prevalence of PFNs. The purpose of this review was to provide an overview of what is known about PFNs. In addition, knowledge gaps in defining PFNs will be discussed. A decision tree to guide clinicians in classifying nodules as PFNs is provided.Supplemental material is available for this article.? RSNA, 2020See also the commentary by White and Rubin in this issue.

Background Chest radiography may play an important role in triage for coronavirus disease 2019 (COVID-19), particularly in low-resource settings. Purpose To evaluate the performance of an artificial intelligence (AI) system for detection of COVID-19 pneumonia on chest radiographs. Materials and Methods An AI system (CAD4COVID-XRay) was trained on 24 678 chest radiographs, including 1540 used only for validation while training. The test set consisted of a set of continuously acquired chest radiographs (n = 454) obtained in patients suspected of having COVID-19 pneumonia between March 4 and April 6, 2020, at one center (223 patients with positive reverse transcription polymerase chain reaction [RT-PCR] results, 231 with negative RT-PCR results). Radiographs were independently analyzed by six readers and by the AI system. Diagnostic performance was analyzed with the receiver operating characteristic curve. Results For the test set, the mean age of patients was 67 years ± 14.4 (standard deviation) (56% male). With RT-PCR test results as the reference standard, the AI system correctly classified chest radiographs as COVID-19 pneumonia with an area under the receiver operating characteristic curve of 0.81. The system significantly outperformed each reader (P < .001 using the McNemar test) at their highest possible sensitivities. At their lowest sensitivities, only one reader significantly outperformed the AI system (P = .04). Conclusion The performance of an artificial intelligence system in the detection of coronavirus disease 2019 on chest radiographs was comparable with that of six independent readers. © RSNA, 2020

Purpose: To study interreader variability for classifying pulmonary opacities at CT as perifissural nodules (PFNs) and determine how reliably radiologists differentiate PFNs from malignancies. Materials and Methods: CT studies were obtained retrospectively from the National Lung Screening Trial (2002-2009). Nodules were eligible for the study if they were noncalcified, solid, within the size range of 5 to 10 mm, and scanned with a section thickness of 2 mm or less. Six radiologists classified 359 nodules in a cancer-enriched data set as PFN, non-PFN, or not applicable. Nodules classified as not applicable by at least three radiologists were excluded, leaving 316 nodules for post-hoc statistical analysis. Results: The study group contained 22.2% cancers (70 of 316). The median proportion of nodules classified as PFNs was 45.6% (144 of 316). All six radiologists uniformly classified 17.7% (56 of 316) of the nodules as PFNs. The Fleiss k was 0.50. Compared with non-PFNs, nodules classified as PFNs were smaller and more often located in the lower lobes and attached to a fissure (P , .001). Thirteen (18.6%) of 70 cancers were misclassified 21 times as PFNs. Individual readers' misclassification rates ranged from 0% (0 of 125) to 4.9% (eight of 163). Of 13 misclassified malignancies, 11 were in the upper lobes and two were attached to a fissure. Conclusion: There was moderate interreader agreement when classifying nodules as perifissural nodules. Less than 2.5% of perifissural nodule classifications were misclassified lung cancers (21 of 865) in this cancer-enriched study. Allowing nodules classified as perifissural nodules to be omitted from additional follow-up in a screening setting could substantially reduce the number of unnecessary scans; excluding perifissural nodules in the upper lobes would greatly decrease the misclassification rate.

Background Debate about the optimal lung cancer screening strategy is ongoing. In this study, previous screening history of the Dutch-Belgian Lung Cancer Screening trial (NELSON) is investigated on if it predicts the screening outcome (test result and lung cancer risk) of the final screening round. Methods 15â €..792 participants were randomised (1:1) of which 7900 randomised into a screening group. CT screening took place at baseline, and after 1, 2 and 2.5â €..years. Initially, three screening outcomes were possible: negative, indeterminate or positive scan result. Probability for screening outcome in the fourth round was calculated for subgroups of participants. Results Based on results of the first three rounds, three subgroups were identified: (1) those with exclusively negative results (n=3856; 73.0%); (2) those with ≥1 indeterminate result, but never a positive result (n=1342; 25.5%); and (3) with ≥1 positive result (n=81; 1.5%). Group 1 had the highest probability for having a negative scan result in round 4 (97.2% vs 94.8% and 90.1%, respectively, p

Contains fulltext : 181941.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To compare the PanCan model, Lung-RADS and the 1.2016 National Comprehensive Cancer Network (NCCN) guidelines for discriminating malignant from benign pulmonary nodules on baseline screening CT scans and the impact diameter measurement methods have on performances. METHODS: From the Danish Lung Cancer Screening Trial database, 64 CTs with malignant nodules and 549 baseline CTs with benign nodules were included. Performance of the systems was evaluated applying the system's original diameter definitions: D(longest-C) (PanCan), D(meanAxial) (NCCN), both obtained from axial sections, and D(mean3D) (Lung-RADS). Subsequently all diameter definitions were applied uniformly to all systems. Areas under the ROC curves (AUC) were used to evaluate risk discrimination. RESULTS: PanCan performed superiorly to Lung-RADS and NCCN (AUC 0.874 vs. 0.813, p = 0.003; 0.874 vs. 0.836, p = 0.010), using the original diameter specifications. When uniformly applying D(longest-C), D(mean3D) and D(meanAxial), PanCan remained superior to Lung-RADS (p < 0.001 - p = 0.001) and NCCN (p < 0.001 - p = 0.016). Diameter definition significantly influenced NCCN's performance with D(longest-C) being the worst (D(longest-C) vs. D(mean3D), p = 0.005; D(longest-C) vs. D(meanAxial), p = 0.016). CONCLUSIONS: Without follow-up information, the PanCan model performs significantly superiorly to Lung-RADS and the 1.2016 NCCN guidelines for discriminating benign from malignant nodules. The NCCN guidelines are most sensitive to nodule size definition. KEY POINTS: * PanCan model outperforms Lung-RADS and 1.2016 NCCN guidelines in identifying malignant pulmonary nodules. * Nodule size definition had no significant impact on Lung-RADS and PanCan model. * 1.2016 NCCN guidelines were significantly superior when using mean diameter to longest diameter. * Longest diameter achieved lowest performance for all models. * Mean diameter performed equivalently when derived from axial sections and from volumetry.

There is a growing interest in the automated analysis of chest X-Ray (CXR) as a sensitive and inexpensive means of screening susceptible populations for pulmonary tuberculosis. In this work we evaluate the latest version of CAD4TB, a commercial software platform designed for this purpose. Version 6 of CAD4TB was released in 2018 and is here tested on a fully independent dataset of 5565 CXR images with GeneXpert (Xpert) sputum test results available (854 Xpert positive subjects). A subset of 500 subjects (50% Xpert positive) was reviewed and annotated by 5 expert observers independently to obtain a radiological reference standard. The latest version of CAD4TB is found to outperform all previous versions in terms of area under receiver operating curve (ROC) with respect to both Xpert and radiological reference standards. Improvements with respect to Xpert are most apparent at high sensitivity levels with a specificity of 76% obtained at a fixed 90% sensitivity. When compared with the radiological reference standard, CAD4TB v6 also outperformed previous versions by a considerable margin and achieved 98% specificity at the 90% sensitivity setting. No substantial difference was found between the performance of CAD4TB v6 and any of the various expert observers against the Xpert reference standard. A cost and efficiency analysis on this dataset demonstrates that in a standard clinical situation, operating at 90% sensitivity, users of CAD4TB v6 can process 132 subjects per day at n average cost per screen of \$5.95 per subject, while users of version 3 process only 85 subjects per day at a cost of \$8.38 per subject. At all tested operating points version 6 is shown to be more efficient and cost effective than any other version., Published in Scientific Reports

Lung-RADS represents a categorical system published by the American College of Radiology to standardise management in lung cancer screening. The purpose of the study was to quantify how well readers agree in assigning Lung-RADS categories to screening CTs; secondary goals were to assess causes of disagreement and evaluate its impact on patient management. For the observer study, 80 baseline and 80 follow-up scans were randomly selected from the NLST trial covering all Lung-RADS categories in an equal distribution. Agreement of seven observers was analysed using Cohen’s kappa statistics. Discrepancies were correlated with patient management, test performance and diagnosis of malignancy within the scan year. Pairwise interobserver agreement was substantial (mean kappa 0.67, 95% CI 0.58–0.77). Lung-RADS category disagreement was seen in approximately one-third (29%, 971) of 3360 reading pairs, resulting in different patient management in 8% (278/3360). Out of the 91 reading pairs that referred to scans with a tumour diagnosis within 1 year, discrepancies in only two would have resulted in a substantial management change. Assignment of lung cancer screening CT scans to Lung-RADS categories achieves substantial interobserver agreement. Impact of disagreement on categorisation of malignant nodules was low. • Lung-RADS categorisation of low-dose lung screening CTs achieved substantial interobserver agreement. • Major cause for disagreement was assigning a different nodule as risk-dominant. • Disagreement led to a different follow-up time in 8% of reading pairs.

PURPOSE: To develop a fully automated algorithm for spleen segmentation and to assess the performance of this algorithm in a large dataset. MATERIALS AND METHODS: In this retrospective study, a three-dimensional deep learning network was developed to segment the spleen on thorax-abdomen CT scans. Scans were extracted from patients undergoing oncologic treatment from 2014 to 2017. A total of 1100 scans from 1100 patients were used in this study, and 400 were selected for development of the algorithm. For testing, a dataset of 50 scans was annotated to assess the segmentation accuracy and was compared against the splenic index equation. In a qualitative observer experiment, an enriched set of 100 scan-pairs was used to evaluate whether the algorithm could aid a radiologist in assessing splenic volume change. The reference standard was set by the consensus of two other independent radiologists. A Mann-Whitney U test was conducted to test whether there was a performance difference between the algorithm and the independent observer. RESULTS: The algorithm and the independent observer obtained comparable Dice scores (P = .834) on the test set of 50 scans of 0.962 and 0.964, respectively. The radiologist had an agreement with the reference standard in 81% (81 of 100) of the cases after a visual classification of volume change, which increased to 92% (92 of 100) when aided by the algorithm. CONCLUSION: A segmentation method based on deep learning can accurately segment the spleen on CT scans and may help radiologists to detect abnormal splenic volumes and splenic volume changes. Supplemental material is available for this article. © RSNA, 2020

Current pulmonary nodule management guidelines are based on nodule volume doubling time, which assumes exponential growth behaviour. However, this is a theory that has never been validated in vivo in the routine-care target population. This study evaluates growth patterns of untreated solid and subsolid lung cancers of various histologies in a non-screening setting. Growth behaviour of pathology-proven lung cancers from two academic centres that were imaged at least three times before diagnosis (n=60) was analysed using dedicated software. Random-intercept random-slope mixed-models analysis was applied to test which growth pattern most accurately described lung cancer growth. Individual growth curves were plotted per pathology subgroup and nodule type. We confirmed that growth in both subsolid and solid lung cancers is best explained by an exponential model. However, subsolid lesions generally progress slower than solid ones. Baseline lesion volume was not related to growth, indicating that smaller lesions do not grow slower compared to larger ones. By showing that lung cancer conforms to exponential growth we provide the first experimental basis in the routine-care setting for the assumption made in volume doubling time analysis., Lung cancers in vivo conform to an exponential growth pattern http://ow.ly/eNqB30iUL7D

ObjectiveTo assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting.MethodsIn two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case–control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model.ResultsAfter the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p99%.DiscussionThe Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations.

Purpose To evaluate whether, and to which extent, experienced radiologists are able to visually correctly differentiate transient from persistent subsolid nodules from a single CT examination alone and to determine CT morphological features to make this differentiation. Materials and methods We selected 86 transient and 135 persistent subsolid nodules from the National Lung Screening Trial (NLST) database. Four experienced radiologists visually assessed a predefined list of morphological features and gave a final judgment on a continuous scale (0-100). To assess observer performance, area under the receiver operating characteristic (ROC) curve was calculated. Statistical differences of morphological features between transient and persistent lesions were calculated using Chi-square. Inter-observer agreement of morphological features was evaluated by percentage agreement. Results Forty-nine lesions were excluded by at least 2 observers, leaving 172 lesions for analysis. On average observers were able to differentiate transient from persistent subsolid nodules ≥ 10 mm with an area under the curve of 0.75 (95% CI 0.67-0.82). Nodule type, lesion margin, presence of a well-defined border, and pleural retraction showed significant differences between transient and persistent lesions in two observers. Average pair-wise percentage agreement for these features was 81%, 64%, 47% and 89% respectively. Agreement for other morphological features varied from 53% to 95%. Conclusion The visual capacity of experienced radiologists to differentiate persistent and transient subsolid nodules is moderate in subsolid nodules larger than 10 mm. Performance of the visual assessment of CT morphology alone is not sufficient to generally abandon a short-term follow-up for subsolid nodules.

Subsolid pulmonary nodules are commonly encountered in lung cancer screening and clinical routine. Compared to other nodule types, subsolid nodules are associated with a higher malignancy probability for which the size and mass of the nodule and solid core are important indicators. However, reliably measuring these characteristics on computed tomography (CT) can be hampered by the presence of vessels encompassed by the nodule, since vessels have similar CT attenuation as solid cores. This can affect treatment decisions and patient management. We present a method based on voxel classification to automatically identify vessels and solid cores in given subsolid nodules on CT. Three experts validated our method on 170 screen-detected subsolid nodules from the Multicentric Italian Lung Disease trial. The agreement between the proposed method and the observers was substantial for vessel detection and moderate for solid core detection, which was similar to the inter-observer agreement. We found a relatively high variability in the inter-observer agreement and low method-observer agreements for delineating the borders of vessels and solid cores, illustrating the difficulty of this task. However, 92.4% of the proposed vessel and 80.6% of the proposed solid core segmentations were labeled as usable in clinical practice by the majority of experts.

Contains fulltext : 154320.pdf (Publisher’s version ) (Open Access) Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3\%) SSNs in 234 participants were detected during the trial. 147 (63\%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5\%) participants available for analysis. The median follow-up time was 95 months (range 20-110). 33 (28\%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes.

PURPOSE: To compare human observers to a mathematically derived computer model for differentiation between malignant and benign pulmonary nodules detected on baseline screening computed tomography (CT) scans.METHODS: A case-cohort study design was chosen. The study group consisted of 300 chest CT scans from the Danish Lung Cancer Screening Trial (DLCST). It included all scans with proven malignancies (n = 62) and two subsets of randomly selected baseline scans with benign nodules of all sizes (n = 120) and matched in size to the cancers, respectively (n = 118). Eleven observers and the computer model (PanCan) assigned a malignancy probability score to each nodule. Performances were expressed by area under the ROC curve (AUC). Performance differences were tested using the Dorfman, Berbaum and Metz method. Seven observers assessed morphological nodule characteristics using a predefined list. Differences in morphological features between malignant and size-matched benign nodules were analyzed using chi-square analysis with Bonferroni correction. A significant difference was defined at p < 0.004.RESULTS: Performances of the model and observers were equivalent (AUC 0.932 versus 0.910, p = 0.184) for risk-assessment of malignant and benign nodules of all sizes. However, human readers performed superior to the computer model for differentiating malignant nodules from size-matched benign nodules (AUC 0.819 versus 0.706, p < 0.001). Large variations between observers were seen for ROC areas and ranges of risk scores. Morphological findings indicative of malignancy referred to border characteristics (spiculation, p < 0.001) and perinodular architectural deformation (distortion of surrounding lung parenchyma architecture, p < 0.001; pleural retraction, p = 0.002).CONCLUSIONS: Computer model and human observers perform equivalent for differentiating malignant from randomly selected benign nodules, confirming the high potential of computer models for nodule risk estimation in population based screening studies. However, computer models highly rely on size as discriminator. Incorporation of other morphological criteria used by human observers to superiorly discriminate size-matched malignant from benign nodules, will further improve computer performance.

Contains fulltext : 165636.pdf (Publisher’s version ) (Closed access) In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial (NELSON).Europe's largest, sufficiently powered randomised lung cancer screening trial was designed to determine whether low-dose CT screening reduces lung cancer mortality by ?25\% compared with no screening after 10?years of follow-up. The screening arm (n=7915) received screening at baseline, after 1 year, 2 years and 2.5?years. Performance of the NELSON screening strategy in the final fourth round was evaluated. Comparisons were made between lung cancers detected in the first three rounds, in the final round and during the 2.5-year interval.In round 4, 46 cancers were screen-detected and there were 28 interval cancers between the third and fourth screenings. Compared with the second round screening (1-year interval), in round 4 a higher proportion of stage IIIb/IV cancers (17.3\% vs 6.8\%, p=0.02) and higher proportions of squamous-cell, bronchoalveolar and small-cell carcinomas (p=0.001) were detected. Compared with a 2-year interval, the 2.5-year interval showed a higher non-significant stage distribution (stage IIIb/IV 17.3\% vs 5.2\%, p=0.10). Additionally, more interval cancers manifested in the 2.5-year interval than in the intervals of previous rounds (28 vs 5 and 28 vs 19).A 2.5-year interval reduced the effect of screening: the interval cancer rate was higher compared with the 1-year and 2-year intervals, and proportion of advanced disease stage in the final round was higher compared with the previous rounds.ISRCTN63545820.

Contains fulltext : 179531.pdf (Publisher’s version ) (Open Access) Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems. 13 p.

Contains fulltext : 174818.pdf (Publisher’s version ) (Open Access) Purpose To evaluate the added value of Lung CT Screening Reporting and Data System (Lung-RADS) assessment category 4X over categories 3, 4A, and 4B for differentiating between benign and malignant subsolid nodules (SSNs). Materials and Methods SSNs on all baseline computed tomographic (CT) scans from the National Lung Cancer Trial that would have been classified as Lung-RADS category 3 or higher were identified, resulting in 374 SSNs for analysis. An experienced screening radiologist volumetrically segmented all solid cores and located all malignant SSNs visible on baseline scans. Six experienced chest radiologists independently determined which nodules to upgrade to category 4X, a recently introduced category for lesions that demonstrate additional features or imaging findings that increase the suspicion of malignancy. Malignancy rates of purely size-based categories and category 4X were compared. Furthermore, the false-positive rates of category 4X lesions were calculated and observer variability was assessed by using Fleiss kappa statistics. Results The observers upgraded 15%-24% of the SSNs to category 4X. The malignancy rate for 4X nodules varied from 46% to 57% per observer and was substantially higher than the malignancy rates of categories 3, 4A, and 4B SSNs without observer intervention (9%, 19%, and 23%, respectively). On average, the false-positive rate for category 4X nodules was 7% for category 3 SSNs, 7% for category 4A SSNs, and 19% for category 4B SSNs. Of the falsely upgraded benign lesions, on average 27% were transient. The agreement among the observers was moderate, with an average kappa value of 0.535 (95% confidence interval: 0.509, 0.561). Conclusion The inclusion of a 4X assessment category for lesions suspicious for malignancy in a nodule management tool is of added value and results in high malignancy rates in the hands of experienced radiologists. Proof of the transient character of category 4X lesions at short-term follow-up could avoid unnecessary invasive management. (c) RSNA, 2017.

The introduction of lung cancer screening programs will produce an unprecedented amount of chest CT scans in the near future, which radiologists will have to read in order to decide on a patient follow-up strategy. According to the current guidelines, the workup of screen-detected nodules strongly relies on nodule size and nodule type. In this paper, we present a deep learning system based on multi-stream multi-scale convolutional networks, which automatically classifies all nodule types relevant for nodule workup. The system processes raw CT data containing a nodule without the need for any additional information such as nodule segmentation or nodule size and learns a representation of 3D data by analyzing an arbitrary number of 2D views of a given nodule. The deep learning system was trained with data from the Italian MILD screening trial and validated on an independent set of data from the Danish DLCST screening trial. We analyze the advantage of processing nodules at multiple scales with a multi-stream convolutional network architecture, and we show that the proposed deep learning system achieves performance at classifying nodule type that surpasses the one of classical machine learning approaches and is within the inter-observer variability among four experienced human observers., Published on Scientific Reports

Background The main challenge in CT screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer. Management protocols use thresholds for nodule size and growth rate to determine which nodules require additional diagnostic procedures, but these should be based on individuals' probabilities of developing lung cancer. In this prespecified analysis, using data from the NELSON CT screening trial, we aimed to quantify how nodule diameter, volume, and volume doubling time affect the probability of developing lung cancer within 2 years of a CT scan, and to propose and evaluate thresholds for management protocols. Methods Eligible participants in the NELSON trial were those aged 50-75 years, who have smoked 15 cigarettes or more per day for more than 25 years, or ten cigarettes or more for more than 30 years and were still smoking, or had stopped smoking less than 10 years ago. Participants were randomly assigned to low-dose CT screening at increasing intervals, or no screening. We included all participants assigned to the screening group who had attended at least one round of screening, and whose results were available from the national cancer registry database. We calculated lung cancer probabilities, stratified by nodule diameter, volume, and volume doubling time and did logistic regression analysis using diameter, volume, volume doubling time, and multinodularity as potential predictor variables. We assessed management strategies based on nodule threshold characteristics for specificity and sensitivity, and compared them to the American College of Chest Physicians (ACCP) guidelines. The NELSON trial is registered at www.trialregister.nl, number ISRCTN63545820. Findings Volume, volume doubling time, and volumetry-based diameter of 9681 non-calcified nodules detected by CT screening in 7155 participants in the screening group of NELSON were used to quantify lung cancer probability. Lung cancer probability was low in participants with a nodule volume of 100 mm 3 or smaller (0.6% [95% CI 0.4-0.8]) or maximum transverse diameter smaller than 5 mm (0.4% [0.2-0.7]), and not significantly different from participants without nodules (0.4% [0.3-0.6], p=0.17 and p=1.00, respectively). Lung cancer probability was intermediate (requiring follow-up CT) if nodules had a volume of 100-300 mm(3) (2.4% [95% CI 1.7-3.5]) or a diameter 5-10 mm (1.3% [1.0-1.8]). Volume doubling time further stratified the probabilities: 0.8% (95% CI 0.4-1.7) for volume doubling times 600 days or more, 4.0% (1.8-8.3) for volume doubling times 400-600 days, and 9.9% (6.9-14.1) for volume doubling times of 400 days or fewer. Lung cancer probability was high for participants with nodule volumes 300 mm 3 or bigger (16.9% [95% CI 14.1-20.0]) or diameters 10 mm or bigger (15.2% [12.7-18.1]). The simulated ACCP management protocol yielded a sensitivity and specificity of 90.9% (95% CI 81.2-96.1), and 87.2% (86.4-87.9), respectively. A diameter-based protocol with volumetry-based nodule diameter yielded a higher sensitivity (92.4% [95% CI 83.1-97.1]), and a higher specificity (90.0% [89.3-90.7). A volume-based protocol (with thresholds based on lung cancer probability) yielded the same sensitivity as the ACCP protocol (90.9% [95% CI 81.2-96.1]), and a higher specificity (94.9% [94.4-95.4]). Interpretation Small nodules (those with a volume = 300 mm(3) or >= 10 mm). Volume doubling time assessment is advocated only for intermediate-sized nodules (with a volume ranging between 100-300 mm(3) or diameter of 5-10 mm). Nodule management protocols based on these thresholds performed better than the simulated ACCP nodule protocol.

Several medical associations recommended lung cancer screening by low-dose computed tomography scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening. In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm(3) and for (part) solid or nonsolid nodules with a volume-doubling time

Contains fulltext : 118196.pdf (Publisher’s version ) (Open Access) OBJECTIVE. The purpose of this study was to investigate a new software program for semiautomatic measurement of the volume and mass of ground-glass nodules (GGNs) in a chest phantom and to investigate the influence of CT scanner, reconstruction filter, tube voltage, and tube current. MATERIALS AND METHODS. We used an anthropomorphic chest phantom with eight artificial GGNs with two different CT attenuations and four different volumes. CT scans were obtained with four models of CT scanner at 120 kVp and 25 mAs with a soft and a sharp reconstruction filter. On the 256-MDCT scanner, the tube current-exposure time product and tube voltage settings were varied. GGNs were measured with software that automatically segmented the nodules. Absolute percentage error (APE) was calculated for volume, mass, and density. Wilcoxon signed rank, Mann-Whitney U, and Kruskal-Wallis tests were used for analysis. RESULTS. Volume and mass did not differ significantly from the true values. When measurements were expressed as APE, the error range was 2-36\% for volume and 5-46\% for mass, which was significantly different from no error. We did not find significant differences in APE between CT scanners with filters for lower tube current for volume or lower tube voltage for mass. CONCLUSION. Computer-aided segmentation and mass and volume measurements of GGNs with the prototype software had promising results in this study.

Contains fulltext : 181940.pdf (Publisher’s version ) (Open Access) PURPOSE: Lung-RADS proposes malignancy probabilities for categories 2 (15%). The purpose of this study was to quantify and compare malignancy rates for Lung-RADS 2 and 4B subsolid nodules (SSNs) on a nodule base. METHODS: We identified all baseline SSNs eligible for Lung-RADS 2 and 4B in the National Lung Screening Trial (NLST) database. Solid cores and nodule locations were annotated using in-house software. Malignant SSNs were identified by an experienced radiologist using NLST information. Malignancy rates and percentages of persistence were calculated. RESULTS: Of the Lung-RADS 2SSNs, 94.3% (1790/1897) could be located on chest CTs. Likewise, 95.1% (331/348) of part-solid nodules >/=6 mm in diameter could be located. Of these, 120 had a solid core >/=8 mm, corresponding to category 4B. Category 2 SSNs showed a malignancy rate of 2.5%, exceeding slightly the proposed rate of

Contains fulltext : 167183.pdf (Publisher’s version ) (Open Access) We present a method for automatic separation and classification of pulmonary arteries and veins in computed tomography. Our method takes advantage of local information to separate segmented vessels, and global information to perform the artery-vein classification. Given a vessel segmentation, a geometric graph is constructed that represents both the topology and the spatial distribution of the vessels. All nodes in the geometric graph where arteries and veins are potentially merged are identified based on graph pruning and individual branching patterns. At the identified nodes, the graph is split into subgraphs that each contain only arteries or veins. Based on the anatomical information that arteries and veins approach a common alveolar sag, an arterial subgraph is expected to be intertwined with a venous subgraph in the periphery of the lung. This relationship is quantified using periphery matching and is used to group subgraphs of the same artery-vein class. Artery-vein classification is performed on these grouped subgraphs based on the volumetric difference between arteries and veins. A quantitative evaluation was performed on 55 publicly available non-contrast CT scans. In all scans, two observers manually annotated randomly selected vessels as artery or vein. Our method was able to separate and classify arteries and veins with a median accuracy of 89%, closely approximating the inter-observer agreement. All CT scans used in this study, including all results of our system and all manual annotations, are publicly available at "http://www.w3.org/1999/xlink">http://arteryvein.grand-challenge.org".

Contains fulltext : 168319.pdf (Publisher’s version ) (Open Access) Automated detection of Tuberculosis (TB) using chest radiographs (CXRs) is gaining popularity due to the lack of trained human readers in resource limited countries with a high TB burden. The majority of the computer-aided detection (CAD) systems for TB focus on detection of parenchymal abnormalities and ignore other important manifestations such as pleural effusion (PE). The costophrenic angle is a commonly used measure for detecting PE, but has limitations. In this work, an automatic method to detect PE in the left and right hemithoraces is proposed and evaluated on a database of 638 CXRs. We introduce a robust way to localize the costophrenic region using the chest wall contour as a landmark structure, in addition to the lung segmentation. Region descriptors are proposed based on intensity and morphology information in the region around the costophrenic recess. Random forest classifiers are trained to classify left and right hemithoraces. Performance of the PE detection system is evaluated in terms of recess localization accuracy and area under the receiver operating characteristic curve (AUC). The proposed method shows significant improvement in the AUC values as compared to systems which use lung segmentation and the costophrenic angle measurement alone.

Purpose: To retrospectively evaluate the performance of consensus double reading compared with single reading at baseline screening of a lung cancer computed tomography (CT) screening trial.Materials and Methods: The study was approved by the Dutch Minister of Health and ethical committees. Written informed consent was obtained from all participants. The benefit of consensus double reading was expressed by the percentage change in cancer detection rate, recall rate, number of additional nodules detected, and change in sensitivity and specificity in 7557 participants. The reference standard was a retrospective analysis of the serial CT scans performed in participants diagnosed with lung cancer during a 2-year period after baseline. Semiautomated volumetric software was used for nodule evaluation. McNemar tests were performed to test statistical significance. In addition, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated and 95% confidence intervals (CIs) constructed.Results: Seventy-four cases of lung cancer were qualified as detectable at baseline. Compared with single reading, consensus double reading did not increase the cancer detection rate (2.7%; 95% CI: -1.0%, 6.4%; P = .50) or change the recall rate (20.6% vs 20.8%, P = .28), but led to the detection of 19.0% (1635 of 8623; 95% CI: 18.0%, 19.9%, P Conclusion: There is no statistically significant benefit for consensus double reading at baseline screening for lung cancer with the use of a nodule management strategy based solely on semiautomated volumetry. (C) RSNA, 2011

BACKGROUND. Computed tomography (CT) screening is an important new tool for the early detection of lung cancer. In the current study, the authors assessed the discomfort associated with CT scanning and the subsequent wait for results and health-related quality of life (HRQoL) over time. METHODS. A total of 351 participants in the Dutch-Belgian randomized controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) who had an appointment for a baseline CT scan were asked to complete questionnaires regarding their experienced discomfort and HRQoL before, 1 day after, and approximately 6 months after the CT scan. HRQoL was measured as generic HRQoL (12-item Short Form [SF-12] and EuroQol questionnaire [EQ-5D]), generic anxiety (State-Trait Anxiety Inventory [STAI-6]), and lung cancer-specific distress (Impact of Event Scale [IES]). Approximately 76.9% of the participants completed all 3 questionnaires. RESULTS. Approximately 87% to 99% of participants reported experiencing no discomfort related to the CT scan. The median SF-12, EQ-5D, STAI-6, and IES scores did not appear to change relevantly over time. Approximately 46.0% and 51.3%, respectively, of the participants reported discomfort in connection with having to wait for the results of the CT scan and dreading those results. These patients had relevantly higher STAI-6 and IES scores (P < .01) (unfavorable) at all 3 assessments. CONCLUSIONS. The current evaluation of the potential adverse effects of CT screening for lung cancer on HRQoL demonstrated no negative effects. However, waiting for the CT scan results was reported to be discomforting by approximately half of the participants. Minimizing the waiting time for the test results is therefore recommended. Cancer 2008. © 2008 American Cancer Society.

Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified Pulmonary nodules.Material and methods: This study was institutional review board approved. For this Study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50 mm(3)) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, Spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer.Results: Of the 469 nodules, 387 (83%) were between 50 and 500 mm(3), 82 (17%) >500 mm(3), 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103 mm(3) (range 50-5486 mm(3)). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43).Conclusion: In solid non-calcified nodules larger than 50 mm(3), size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

In this paper, we tackle the problem of automatic classification of pulmonary peri-fissural nodules (PFNs). The classification problem is formulated as a machine learning approach, where detected nodule candidates are classified as PFNs or non-PFNs. Supervised learning is used, where a classifier is trained to label the detected nodule. The classification of the nodule in 3D is formulated as an ensemble of classifiers trained to recognize PFNs based on 2D views of the nodule. In order to describe nodule morphology in 2D views, we use the output of a pre-trained convolutional neural network known as OverFeat. We compare our approach with a recently presented descriptor of pulmonary nodule morphology, namely Bag of Frequencies, and illustrate the advantages offered by the two strategies, achieving performance of AUC = 0.868, which is close to the one of human experts. (C) 2015 Elsevier B.V. All rights reserved.

We present a fully automatic method for the assessment of spiculation of pulmonary nodules in low-dose Computed Tomography (CT) images. Spiculation is considered as one of the indicators of nodule malignancy and an important feature to assess in order to decide on a patient-tailored follow-up procedure. For this reason, lung cancer screening scenario would benefit from the presence of a fully automatic system for the assessment of spiculation. The presented framework relies on the fact that spiculated nodules mainly differ from non-spiculated ones in their morphology. In order to discriminate the two categories, information on morphology is captured by sampling intensity profiles along circular patterns on spherical surfaces centered on the nodule, in a multi-scale fashion. Each intensity profile is interpreted as a periodic signal, where the Fourier transform is applied, obtaining a spectrum. A library of spectra is created by clustering data via unsupervised learning. The centroids of the clusters are used to label back each spectrum in the sampling pattern. A compact descriptor encoding the nodule morphology is obtained as the histogram of labels along all the spherical surfaces and used to classify spiculated nodules via supervised learning. We tested our approach on a set of nodules from the Danish Lung Cancer Screening Trial (DLCST) dataset. Our results show that the proposed method outperforms other 3-D descriptors of morphology in the automatic assessment of spiculation.

Contains fulltext : 153984.pdf (Publisher’s version ) (Open Access) The purpose of this study was to develop and validate a computer-aided diagnosis (CAD) tool for automatic classification of pulmonary nodules seen on low-dose computed tomography into solid, part-solid, and non-solid. Study lesions were randomly selected from 2 sites participating in the Dutch-Belgian NELSON lung cancer screening trial. On the basis of the annotations made by the screening radiologists, 50 part-solid and 50 non-solid pulmonary nodules with a diameter between 5 and 30 mm were randomly selected from the 2 sites. For each unique nodule, 1 low-dose chest computed tomographic scan was randomly selected, in which the nodule was visible. In addition, 50 solid nodules in the same size range were randomly selected. A completely automatic 3-dimensional segmentation-based classification system was developed, which analyzes the pulmonary nodule, extracting intensity-, texture-, and segmentation-based features to perform a statistical classification. In addition to the nodule classification by the screening radiologists, an independent rating of all nodules by 3 experienced thoracic radiologists was performed. Performance of CAD was evaluated by comparing the agreement between CAD and human experts and among human experts using the Cohen κ statistics.Pairwise agreement for the differentiation between solid, part-solid, and non-solid nodules between CAD and each of the human experts had a κ range between 0.54 and 0.72. The interobserver agreement among the human experts was in the same range (κ range, 0.56-0.81). A novel automated classification tool for pulmonary nodules achieved good agreement with the human experts, yielding κ values in the same range as the interobserver agreement. Computer-aided diagnosis may aid radiologists in selecting the appropriate workup for pulmonary nodules.

Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826–0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. • High accuracy in logistic modelling for lung cancer risk stratification of nodules. • Lung cancer risk prediction is primarily based on size of pulmonary nodules. • Nodule spiculation, age and family history of lung cancer are significant predictors. • Sex does not appear to be a useful risk predictor.

Purpose: To retrospectively determine interobserver variability of semiautomated volume measurements of pulmonary nodules and the potential reasons for variability. Materials and Methods: The Dutch-Belgian lung cancer screening trial (NELSON) is a lung cancer screening study that includes men between the ages of 50 and 75 years who are current or former heavy smokers. The NELSON project was approved by the Dutch Ministry of Health and the ethics committee of each participating hospital. Informed consent was obtained from all participants. For this study, the authors evaluated 1200 consecutive low-dose computed tomographic (CT) scans of the chest obtained during the NELSON project and identified subjects who had at least one 50-500-mm(3) nodule. One local and one central observer independently evaluated the scans and measured the volume of any detected nodule by using semiautomated software. Noncalcified solid nodules with volumes of 15-500 mm(3) were included in this study if they were fully surrounded by air (intraparenchymal) and were detected by both observers. The mean volume and the difference between both measurements were calculated for all nodules. Intermeasurement agreement was assessed with the Spearman correlation coefficient. Potential reasons for discrepancies were assessed. Results: There were 232 men (mean age, 60 years; age range, 52-73 years) with 430 eligible nodules (mean volume, 77.8 mm3; range, 15.3-499.5 mm3). Interobserver correlation was high (r = 0.99). No difference in volume was seen for 383 nodules (89.1%). Discrepant results were obtained for 47 nodules (10.9%); in 16 cases (3.7%), the discrepancy was larger than 10%. The most frequent cause of variability was incomplete segmentation due to an irregular shape or irregular margins. Conclusion: In a minority (approximately 11%) of small solid intraparenchymal nodules, semiautomated measurements are not completely reproducible and, thus, may cause errors in the assessment of nodule growth. For small or irregularly shaped nodules, an observer should check the segmentation shown by the program.

Contains fulltext : 136826.pdf (Publisher’s version ) (Open Access) Subsolid pulmonary nodules occur less often than solid pulmonary nodules, but show a much higher malignancy rate. Therefore, accurate detection of this type of pulmonary nodules is crucial. In this work, a computer-aided detection (CAD) system for subsolid nodules in computed tomography images is presented and evaluated on a large data set from a multi-center lung cancer screening trial. The paper describes the different components of the CAD system and presents experiments to optimize the performance of the proposed CAD system. A rich set of 128 features is defined for subsolid nodule candidates. In addition to previously used intensity, shape and texture features, a novel set of context features is introduced. Experiments show that these features significantly improve the classification performance. Optimization and training of the CAD system is performed on a large training set from one site of a lung cancer screening trial. Performance analysis on an independent test from another site of the trial shows that the proposed system reaches a sensitivity of 80% at an average of only 1.0 false positive detections per scan. A retrospective analysis of the output of the CAD system by an experienced thoracic radiologist shows that the CAD system is able to find subsolid nodules which were not contained in the screening database.

Background: A prospective study was done to investigate the occurrence of morphologic changes after ERCP that present as pancreatic pseudotumor on CT scan. Fifty-eight patients underwent CT before and after ERCP. In addition, post-ERCP complications and the value of routinely obtained CT before ERCP were assessed. Results: Thirty-nine patients could be fully analyzed; 12 underwent a papillotomy (group 1). Pseudotumor of the pancreatic head was demonstrated on CT after ERCP in 2 of them (17%). No changes were seen in the 27 patients who underwent diagnostic ERCP (group 2) ( p = 0.048). Asymptomatic retroperitoneal perforation after papillotomy was diagnosed in 3 patients (13%). Routinely obtained CT scans before ERCP defined a specific etiology of the biliary obstruction in 12% of patients not suggested by ultrasound. Duodenal diverticulum was found in 4 patients, resulting in a sensitivity of 36% and a specificity of 100% for CT. Oral contrast (600 ml) administered a few hours before endoscopy never hampered the endoscopist. Conclusion: Pancreatic pseudotumor on CT after ERCP occurred only when papillotomy was performed. CT remains a valuable diagnostic tool after diagnostic ERCP. Asymptomatic perforation may occur following ERCP with papillotomy. Routinely obtained CT before ERCP was not profitable for the endoscopist in more than 80% of our patients. (Gastrointest Endosc 1997;45:231-5.)

Rationale The NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek) trial is, with 15,822 participants, the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening, and an increasing length of screening interval are particular features of the NELSON trial.Objectives: To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of screendetected lung cancers, and to compare this across screening rounds, between sexes, and with other screening trials.Methods: All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the sexes, and with other screening trials.Measurements and Main Results: In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. Of these lung cancers, 70.8% were diagnosed at stage I and 8.1% at stage IIIB-IV, and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology, or tumor localization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared with other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV.Conclusions: Despite stringent criteria for a positive screening, an increasing length of screening interval, and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is essential for the effectiveness of our screening strategy.Clinical trial registered with www.trialregister.nl (ISRCTN63545820).

Contains fulltext : 118875.pdf (Publisher’s version ) (Closed access) Objective: To compare various visualization techniques for the detection of non-solid nodules in low-dose lung cancer screening computed tomography (CT) scans. Methods: An enriched sample of 216 male lung cancer screening subjects aged 60.4 ± 6.0 years was used. Two blinded independent readers searched for non-solid nodules on 5-mm multiplanar reconstructions, 1-mm slices and 7-mm maximum intensity projections (trial protocol). The reference standard was a consensus diagnosis of all non-solid nodules reported at least once. Results: Twenty-three individuals (10.6\%) had in total 34 non-solid nodules. Interobserver agreement was good (Cohen kappa 0.89-0.95). For both observers, we found no differences between the 3 viewing techniques (P > 0.13). Conclusion: In low-dose lung cancer screening CT scans, we were unable to find a viewing technique superior to that used in the trial by experienced observers who focused on non-solid nodule detection.

Contains fulltext : 110186.pdf (Publisher’s version ) (Open Access) BACKGROUND: Incidental CT findings may provide an opportunity for early detection of chronic obstructive pulmonary disease (COPD), which may prove important in CT-based lung cancer screening setting. We aimed to determine the diagnostic performance of human observers to visually evaluate COPD presence on CT images, in comparison to automated evaluation using quantitative CT measures. METHODS: This study was approved by the Dutch Ministry of Health and the institutional review board. All participants provided written informed consent. We studied 266 heavy smokers enrolled in a lung cancer screening trial. All subjects underwent volumetric inspiratory and expiratory chest computed tomography (CT). Pulmonary function testing was used as the reference standard for COPD. We evaluated the diagnostic performance of eight observers and one automated model based on quantitative CT measures. RESULTS: The prevalence of COPD in the study population was 44% (118/266), of whom 62% (73/118) had mild disease. The diagnostic accuracy was 74.1% in the automated evaluation, and ranged between 58.3% and 74.3% for the visual evaluation of CT images. The positive predictive value was 74.3% in the automated evaluation, and ranged between 52.9% and 74.7% for the visual evaluation. Interobserver variation was substantial, even within the subgroup of experienced observers. Agreement within observers yielded kappa values between 0.28 and 0.68, regardless of the level of expertise. The agreement between the observers and the automated CT model showed kappa values of 0.12-0.35. CONCLUSIONS: Visual evaluation of COPD presence on chest CT images provides at best modest accuracy and is associated with substantial interobserver variation. Automated evaluation of COPD subjects using quantitative CT measures appears superior to visual evaluation by human observers.