Search

Screening with low-dose CT (LDCT) in a high-risk population, as defined by age and smoking behavior, reduces lung cancer-related mortality. However, LDCT screening presents a major challenge. Numerous, mostly benign, nodules are seen in the lungs during screening. The question is how to distinguish the malignant from the benign nodules. Various studies use different protocols for nodule management. The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, the largest European lung cancer screening trial, used distinctions based on nodule volumetric assessment and growth rate. This review discusses key findings from the NELSON study regarding the characteristics of screening-detected nodules, including nodule size and its volumetric assessment, growth rate, subtype, and their associated malignancy risk. These results are compared with findings from other screening studies and current recommendations for lung nodule management. By examining differences in nodule management strategies and providing a comprehensive overview of outcomes specific to lung cancer screening, this review aims to contribute to the broader discussion on optimizing lung nodule management in screening programs., (© RSNA, 2024.)

Background Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population. Purpose To study the prevalence and size distribution of solid lung nodules by age and sex in a nonsmoking population. Materials and Methods Participants included nonsmokers (never or former smokers) from the population-based Imaging in Lifelines study conducted in the Northern Netherlands. Participants (age ≥ 45 years) with completed lung function tests underwent chest low-dose CT scans. Seven trained readers registered the presence and size of solid lung nodules measuring 30 mm 3 or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm 3 ), clinically relevant lung nodules (≥100 mm 3 ), and actionable nodules (≥300 mm 3 ) are presented by 5-year categories and by sex. Results A total of 10 431 participants (median age, 60.4 years [IQR, 53.8-70.8 years]; 56.6% [ n = 5908] female participants; 46.1% [ n = 4812] never smokers and 53.9% [ n = 5619] former smokers) were included. Of these, 42.0% ( n = 4377) had at least one lung nodule (male participants, 47.5% [2149 of 4523]; female participants, 37.7% [2228 of 5908]). The prevalence of lung nodules increased from age 45-49.9 years (male participants, 39.4% [219 of 556]; female participants, 27.7% [236 of 851]) to age 80 years or older (male participants, 60.7% [246 of 405]; female participants, 50.9% [163 of 320]). Clinically relevant lung nodules were present in 11.1% (1155 of 10 431) of participants, with prevalence increasing with age (male participants, 8.5%-24.4%; female participants, 3.7%-15.6%), whereas actionable nodules were present in 1.1%-6.4% of male participants and 0.6%-4.9% of female participants. Conclusion Lung nodules were present in a substantial proportion of all age groups in the Northern European nonsmoking population, with slightly higher prevalence for male participants than female participants. © RSNA, 2024 Supplemental material is available for this article.

Purpose: We determine and compare the prevalence, subtypes, severity, and risk factors for emphysema assessed by low-dose CT(LDCT) in Chinese and Dutch general populations., Methods: This cross-sectional study included LDCT scans of 1143 participants between May and October 2017 from a Chinese Cohort study and 1200 participants with same age range and different smoking status between May and October 2019 from a Dutch population-based study. An experienced radiologist visually assessed the scans for emphysema presence (≥trace), subtype, and severity. Logistic regression analyses, overall and stratified by smoking status, were performed and adjusted for fume exposure, demographic and smoking data., Results: The Chinese population had a comparable proportion of women to the Dutch population (54.9 % vs 58.9 %), was older (61.7 ± 6.3 vs 59.8 ± 8.1), included more never smokers (66.4 % vs 38.3 %), had a higher emphysema prevalence ([58.8 % vs 39.7 %], adjusted odds ratio, aOR = 2.06, 95 %CI = 1.68-2.53), and more often had centrilobular emphysema (54.8 % vs 32.8 %, p < 0.001), but no differences in emphysema severity. After stratification, only in never smokers an increased odds of emphysema was observed in the Chinese compared to the Dutch (aOR = 2.55, 95 %CI = 1.95-3.35). Never smokers in both populations shared older age (aOR = 1.59, 95 %CI = 1.25-2.02 vs 1.26, 95 %CI = 0.97-1.64) and male sex (aOR = 1.50, 95 %CI = 1.02-2.22 vs 1.93, 95 %CI = 1.26-2.96) as risk factors for emphysema., Conclusions: Only never smokers had a higher prevalence of mainly centrilobular emphysema in the Chinese general population compared to the Dutch after adjusting for confounders, indicating that factors other than smoking, age and sex contribute to presence of CT-defined emphysema., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population., Methods: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (age ≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume ≥30 mm 3 ) and 2) a clinically relevant lung nodule (volume ≥100 mm 3 ). Fully adjusted multivariable logistic regression models were applied overall and stratified by smoking status to identify independent risk factors for the presence of nodules., Results: Among the 12 055 participants (44.1% male; median age 60 years; 39.9% never-smokers; 98.7% White), we found lung nodules in 41.8% (5045 out of 12 055) and clinically relevant nodules in 11.4% (1377 out of 12 055); the corresponding figures among never-smokers were 38.8% and 9.5%, respectively. Factors independently associated with increased odds of having any lung nodule included male sex, older age, low educational level, former smoking, asbestos exposure and COPD. Among never-smokers, a family history of lung cancer increased the odds of both lung nodules and clinically relevant nodules. Among former and current smokers, low educational level was positively associated with lung nodules, whereas being overweight was negatively associated. Among current smokers, asbestos exposure and low physical activity were associated with clinically relevant nodules., Conclusions: The study provides a large-scale evaluation of lung nodules and associated risk factors in a Western European general population: lung nodules and clinically relevant nodules were prevalent, and never-smokers with a family history of lung cancer were a non-negligible group., Competing Interests: Conflict of interest: M. Vonder is a researcher for the Institute for DiagNostic Accuracy, Groningen, the Netherlands. The remaining authors declare no conflicts of interest., (Copyright ©The authors 2024.)

Background CT-derived bronchial parameters have been linked to chronic obstructive pulmonary disease and asthma severity, but little is known about these parameters in healthy individuals. Purpose To investigate the distribution of bronchial parameters at low-dose CT in individuals with healthy lungs from a Dutch general population. Materials and Methods In this prospective study, low-dose chest CT performed between May 2017 and October 2022 were obtained from participants who had completed the second-round assessment of the prospective, longitudinal Imaging in Lifelines study. Participants were aged at least 45 years, and those with abnormal spirometry, self-reported respiratory disease, or signs of lung disease at CT were excluded. Airway lumens and walls were segmented automatically. The square root of the bronchial wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10), luminal area (LA), wall thickness (WT), and wall area percentage were calculated. Associations between sex, age, height, weight, smoking status, and bronchial parameters were assessed using univariable and multivariable analyses. Results The study sample was composed of 8869 participants with healthy lungs (mean age, 60.9 years ± 10.4 [SD]; 4841 [54.6%] female participants), including 3672 (41.4%) never-smokers and 1197 (13.5%) individuals who currently smoke. Bronchial parameters for male participants were higher than those for female participants (Pi10, slope [β] range = 3.49-3.66 mm; LA, β range = 25.40-29.76 mm 2 ; WT, β range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT ( r 2 range = 0.06-0.09, 0.02-0.01, and 0.02-0.07, respectively; all P < .001). Never-smoking individuals had the lowest Pi10 followed by formerly smoking and currently smoking individuals (3.62 mm ± 0.13, 3.68 mm ± 0.14, and 3.70 mm ± 0.14, respectively; all P < .001). In multivariable regression models, age, sex, height, weight, and smoking history explained up to 46% of the variation in bronchial parameters. Conclusion In healthy individuals, bronchial parameters differed by sex, height, weight, and smoking history; male sex and increasing age were associated with wider lumens and thicker walls. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Emrich and Varga-Szemes in this issue.

Objectives: Multiple lung cancer screening studies reported the performance of Lung CT Screening Reporting and Data System (Lung-RADS), but none systematically evaluated its performance across different populations. This systematic review and meta-analysis aimed to evaluate the performance of Lung-RADS (versions 1.0 and 1.1) for detecting lung cancer in different populations., Methods: We performed literature searches in PubMed, Web of Science, Cochrane Library, and Embase databases on October 21, 2022, for studies that evaluated the accuracy of Lung-RADS in lung cancer screening. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and heterogeneity was explored in stratified and meta-regression analyses., Results: A total of 31 studies with 104,224 participants were included. For version 1.0 (27 studies, 95,413 individuals), pooled sensitivity was 0.96 (95% confidence interval [CI]: 0.90-0.99) and pooled specificity was 0.90 (95% CI: 0.87-0.92). Studies in high-risk populations showed higher sensitivity (0.98 [95% CI: 0.92-0.99] vs. 0.84 [95% CI: 0.50-0.96]) and lower specificity (0.87 [95% CI: 0.85-0.88] vs. 0.95 (95% CI: 0.92-0.97]) than studies in general populations. Non-Asian studies tended toward higher sensitivity (0.97 [95% CI: 0.91-0.99] vs. 0.91 [95% CI: 0.67-0.98]) and lower specificity (0.88 [95% CI: 0.85-0.90] vs. 0.93 [95% CI: 0.88-0.96]) than Asian studies. For version 1.1 (4 studies, 8811 individuals), pooled sensitivity was 0.91 (95% CI: 0.83-0.96) and specificity was 0.81 (95% CI: 0.67-0.90)., Conclusion: Among studies using Lung-RADS version 1.0, considerable heterogeneity in sensitivity and specificity was noted, explained by population type (high risk vs. general), population area (Asia vs. non-Asia), and cancer prevalence., Clinical Relevance Statement: Meta-regression of lung cancer screening studies using Lung-RADS version 1.0 showed considerable heterogeneity in sensitivity and specificity, explained by the different target populations, including high-risk versus general populations, Asian versus non-Asian populations, and populations with different lung cancer prevalence., Key Points: • High-risk population studies showed higher sensitivity and lower specificity compared with studies performed in general populations by using Lung-RADS version 1.0. • In non-Asian studies, the diagnostic performance of Lung-RADS version 1.0 tended to be better than in Asian studies. • There are limited studies on the performance of Lung-RADS version 1.1, and evidence is lacking for Asian populations., (© 2023. The Author(s).)

Assessment of image noise is a relevant issue in computed tomography (CT). Noise is routinely measured by the standard deviation of density values (Hounsfield units, HU) within a circular region of interest (ROI). We explored the effect of a spherical volume of interest (VOI) on noise measurements. Forty-nine chronic obstructive pulmonary disease patients underwent CT with clinical protocol (regular dose [RD], volumetric CT dose index [CTDIvol] 3.04 mGy, 64-slice unit), and ultra-low dose (ULD) protocol (median CTDIvol 0.38 mGy, dual-source unit). Noise was measured in 27 1-cm 2 ROIs and 27 0.75-cm 3 VOIs inside the trachea. Median true noise was 21 HU (range 17-29) for RD-CT and 33 HU (26-39) for ULD-CT. The VOI approach resulted in a lower mean distance between limits of agreement compared to ROI: 5.9 versus 10.0 HU for RD-CT (-40%); 4.7 versus 9.9 HU for ULD-CT (-53%). Mean systematic bias barely changed: -1.6 versus -0.9HU for RD-CT; 0.0 to 0.4HU for ULD-CT. The average measurement time was 6.8 s (ROI) versus 9.7 (VOI), independent of dose level. For chest CT, measuring noise with a VOI-based instead of a ROI-based approach reduces variability by 40-53%, without a relevant effect on systematic bias and measurement time., (© 2021. The Author(s).)

We investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March. All lung nodules with volume of ≥ 30 mm 3 (approximately 3 mm in diameter) were registered. In total, 2496 lung nodules were found in 1312 (38%) of the 3456 included participants (nodules per participant ranging from 1 to 21, median 1). In summer, 711 (54%) participants had 1 or more lung nodule(s) compared to 601 (46%) participants in winter (p = 0.002). Of the spherical, perifissural and left-upper-lobe nodules, relatively more were detected in winter, whereas of the polygonal-, irregular-shaped and centrally-calcified nodules, relatively more were detected in summer. Various seasonal diseases with inflammation as underlying pathophysiology may influence presence and characteristics of lung nodules. Further investigation into underlying pathophysiology using short-term LDCT follow-up could help optimize the management strategy for CT-detected lung nodules in clinical practice.

Background: Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality. The aim of this study was to evaluate the cost-effectiveness of lung cancer screening with LDCT in a high-risk population., Methods: The study used an adapted microsimulation model in a cohort of Dutch heavy smokers for a lifetime horizon from a health insurance perspective. The main outcomes included average cost-effectiveness ratio (ACER), incremental cost-effectiveness ratio (ICER) and lung cancer mortality reduction. The comparator was no screening. Scenarios with different screening intervals and starting and stopping ages were evaluated for 100,000 male heavy smokers and 100,000 female heavy smokers. A cost-effectiveness threshold of 60 k€ per life year gained (LYG) was assumed acceptable., Results: The evaluated screening scenarios yielded ACERs ranging from 17.7 to 32.4 k€/LYG for men and from 17.8 to 32.1 k€/LYG for women. The lung cancer mortality reduction ranged from 9.3% to 16.8% for men and from 7.8% to 13.7% for women. The optimal screening scenario was annual screening from 55 to 80 years for men and biennial screening from 50 to 80 years for women, with an ICER of 51.6 and 45.8 k€ per LYG compared with its previous efficient alternative, respectively. Compared with no screening, the optimal screening scenario yielded an ICER of 27.6 k€/LYG for men and 21.1 k€/LYG for women. The mortality reduction of lung cancer was 15.9% for men and 10.6% for women., Conclusions: Lung cancer LDCT screening is cost-effective in a high-risk population. The optimal screening scenario is dependent on sex., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Coronary artery calcium (CAC) score has shown to be an accurate predictor of future cardiovascular events. Early detection by CAC scoring might reduce the number of deaths by cardiovascular disease (CVD). Automatically excluding scans which test negative for CAC could significantly reduce the workload of radiologists. We propose an algorithm that both excludes negative scans and segments the CAC., Method: The training and internal validation data were collected from the ROBINSCA study. The external validation data were collected from the ImaLife study. Both contain annotated low-dose non-contrast cardiac CT scans. 60 scans of participants were used for training and 2 sets of 50 CT scans of participants without CAC and 50 CT scans of participants with an Agatston score between 10 and 20 were collected for both internal and external validation. The effect of dilated convolutional layers was tested by using 2 CNN architectures. We used the patient-level accuracy as metric for assessing the accuracy of our pipeline for detection of CAC and the Dice coefficient score as metric for the segmentation of CAC., Results: Of the 50 negative cases in the internal and external validation set, 62 % and 86 % were classified correctly, respectively. There were no false negative predictions. For the segmentation task, Dice Coefficient scores of 0.63 and 0.84 were achieved for the internal and external validation datasets, respectively., Conclusions: Our algorithm excluded 86 % of all scans without CAC. Radiologists might need to spend less time on participants without CAC and could spend more time on participants that need their attention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the optimal window setting to diagnose the invasiveness of lung adenocarcinoma in sub-solid nodules (SSNs)., Methods: We retrospectively included 437 SSNs and randomly divided them 3:1 into a training group (327) and a testing group (110). The presence of a solid component was regarded as indicator of invasiveness. At fixed window level (WL) of 35 Hounsfield Units (HU), two readers adjusted the window width (WW) in the training group and recorded once a solid component appeared or disappeared on CT images acquired at 120 kVp. The optimal WW cut-off value to differentiate between invasive and pre-invasive lesions, based on the receiver operating characteristic (ROC) curve, was defined as "core" WW. The diagnostic performances of the mediastinal window setting (WW/WL, 350/35 HU) and core window setting were then compared in the testing group., Results: Of the 437 SSNs, 88 were pre-invasive [17 atypical adenomatous hyperplasia (AAH) and 71 adenocarcinoma in situ (AIS)], 349 were invasive [233 minimally invasive adenocarcinoma (MIA), 116 invasive adenocarcinoma (IA)]. In training group, the core WW of 1175 HU was the optimal cut-off to detect solid components of SSNs (AUC:0.79). In testing group, the sensitivity, specificity, positive, negative predictive value, and diagnostic accuracy for SSN invasiveness were 49.4%, 90.5%, 95.7%, 29.7%, and 57.3% for mediastinal window setting, and 87.6%, 76.2%, 91.6%, 76.2%, and 85.5% for core window setting., Conclusion: At 120 kVp, core window setting (WW/WL, 1175/35 HU) outperformed the traditional mediastinal window setting to diagnose the invasiveness of SSNs., Competing Interests: Declaration of Competing Interest All other authors declare that that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Research into the possibilities of AI in cardiac CT has been growing rapidly in the last decade. With the rise of publicly available databases and AI algorithms, many researchers and clinicians have started investigations into the use of AI in the clinical workflow. This review is a comprehensive overview on the types of tasks and applications in which AI can aid the clinician in cardiac CT, and can be used as a primer for medical researchers starting in the field of AI. The applications of AI algorithms are explained and recent examples in cardiac CT of these algorithms are further elaborated on. The critical factors for implementation in the future are discussed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To develop an imaging reporting system for the classification of 3 adenocarcinoma subtypes of computed tomography (CT)-detected subsolid pulmonary nodules (SSNs) in clinical patients., Methods: Between November 2011 and October 2017, 437 pathologically confirmed SSNs were retrospectively identified. SSNs were randomly divided 2:1 into a training group (291 cases) and a testing group (146 cases). CT-imaging characteristics were analyzed using multinomial univariable and multivariable logistic regression analysis to identify discriminating factors for the 3 adenocarcinoma subtypes (pre-invasive lesions, minimally invasive adenocarcinoma, and invasive adenocarcinoma). These factors were used to develop a classification and regression tree model. Finally, an SSN Imaging Reporting System (SSN-IRS) was constructed based on the optimized classification model. For validation, the classification performance was evaluated in the testing group., Results: Of the CT-derived characteristics of SSNs, qualitative density (nonsolid or part-solid), core (non-core or core), semantic features (pleural indentation, vacuole sign, vascular invasion), and diameter of solid component (≤6 mm or >6 mm), were the most important factors for the SSN-IRS. The total sensitivity, specificity, and diagnostic accuracy of the SSN-IRS was 89.0% (95% confidence interval [CI], 84.8%-92.4%), 74.6% (95% CI, 70.8%-78.1%), and 79.4% (95% CI, 76.5%-82.0%) in the training group and 84.9% (95% CI, 78.1%-90.3%), 68.5% (95% CI, 62.8%-73.8%), and 74.0% (95% CI, 69.6%-78.0%) in the testing group, respectively., Conclusions: The SSN-IRS can classify 3 adenocarcinoma subtypes using CT-based characteristics of subsolid pulmonary nodules. This classification tool can help clinicians to make follow-up recommendations or decisions for surgery in clinical patients with SSNs., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

Background: Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre-treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty., Methods: A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non-gender specific thresholds (<43.2 cm 2 /m 2 ). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross-sectional measurements was excellent for both intra-observer variability (r = 0.99, P < 0.001) and inter-observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66-0.89, P < 0.001 and OR 0.76, 95% CI 0.66-0.88, P < 0.001, respectively)., Conclusions: This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease are highly prevalent in the general population and expected to cause most deaths by 2050. For these "Big-3," treatment might cure, delay, or stop the progression of disease at a very early stage. Lung nodule growth rate (a biomarker for lung cancer), emphysema/air trapping (a biomarker for chronic obstructive pulmonary disease), and coronary artery calcification (a biomarker for cardiovascular disease) are imaging biomarkers of early stages of the Big-3 that can be acquired with low-dose computed tomography (CT). We hypothesize that a (combined) low-dose CT examination for detection of all 3 diseases may significantly improve the cost-effectiveness of screening in the future. We review the current evidence of the imaging biomarkers for the detection of the Big-3 diseases and present the potential health economic potential of Big-3 screening. Furthermore, we review the low-dose CT protocols to acquire these biomarkers and describe the technical considerations when combining the CT protocols for the different biomarkers.

Purpose: New nodules after baseline are regularly found in low-dose CT lung cancer screening and have a high lung cancer probability. It is unknown whether morphological and location characteristics can improve new nodule risk stratification by size., Methods: Solid non-calcified nodules detected during incidence screening rounds of the randomised controlled Dutch-Belgian lung cancer screening (NELSON) trial and registered as new or previously below detection limit (15 mm 3 ) were included. A multivariate logistic regression analysis with lung cancer as outcome was performed, including previously established volume cut-offs (<30 mm 3 , 30-<200 mm 3 and ≥200 mm 3 ) and nodule characteristics (location, distribution, shape, margin and visibility <15 mm 3 in retrospect)., Results: Overall, 1280 new nodules were included with 73 (6%) being lung cancer. Of nodules ≥30 mm 3 at detection and visible <15 mm 3 in retrospect, 22% (6/27) were lung cancer. Discrimination based on volume cut-offs (area under the receiver operating characteristic curve (AUC): 0.80, 95% CI 0.75 to 0.84) and continuous volume (AUC: 0.82, 95% CI 0.77 to 0.87) was similar. After adjustment for volume cut-offs, only location in the right upper lobe (OR 2.0, P=0.012), central distribution (OR 2.4, P=0.001) and visibility <15 mm 3 in retrospect (OR 4.7, P=0.003) remained significant predictors for lung cancer. The Hosmer-Lemeshow test (P=0.75) and assessment of bootstrap calibration curves indicated adequate model fit. Discrimination based on the continuous model probability (AUC: 0.85, 95% CI 0.81 to 0.89) was superior to volume cut-offs alone, but when stratified into three risk groups (AUC: 0.82, 95% CI 0.78 to 0.86), discrimination was similar., Conclusion: Contrary to morphological nodule characteristics, growth-independent characteristics may further improve volume-based new nodule lung cancer prediction, but in a three-category stratification approach, this is limited., Trial Registration Number: ISRCTN63545820; pre-results., Competing Interests: Competing interests: CMvdA reports grants from Symposium Thoracic Oncology, grants from American Thoracic Society, grants from Lancet Respiratory Medicine, outside the submitted work. KN reports grants from Flemish League against Cancer, grants from the Belgian Foundation against Cancer, during the conduct of the study. HJMG reports grants from Eli Lilly, Roche, MSD, BMS and Novartis, outside the submitted work. HJdK took part in a 1-day advisory meeting on biomarkers organised by M.D. Anderson/Health Sciences during the 16th World Conference on Lung Cancer, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To explore the relationship between nodule count and lung cancer probability in baseline low-dose CT lung cancer screening., Materials and Methods: Included were participants from the NELSON trial with at least one baseline nodule (3392 participants [45% of screen-group], 7258 nodules). We determined nodule count per participant. Malignancy was confirmed by histology. Nodules not diagnosed as screen-detected or interval cancer until the end of the fourth screening round were regarded as benign. We compared lung cancer probability per nodule count category., Results: 1746 (51.5%) participants had one nodule, 800 (23.6%) had two nodules, 354 (10.4%) had three nodules, 191 (5.6%) had four nodules, and 301 (8.9%) had>4 nodules. Lung cancer in a baseline nodule was diagnosed in 134 participants (139 cancers; 4.0%). Median nodule count in participants with only benign nodules was 1 (Inter-quartile range [IQR]: 1-2), and 2 (IQR 1-3) in participants with lung cancer (p=NS). At baseline, malignancy was detected mostly in the largest nodule (64/66 cancers). Lung cancer probability was 62/1746 (3.6%) in case a participant had one nodule, 33/800 (4.1%) for two nodules, 17/354 (4.8%) for three nodules, 12/191 (6.3%) for four nodules and 10/301 (3.3%) for>4 nodules (p=NS)., Conclusion: In baseline lung cancer CT screening, half of participants with lung nodules have more than one nodule. Lung cancer probability does not significantly change with the number of nodules. Baseline nodule count will not help to differentiate between benign and malignant nodules. Each nodule found in lung cancer screening should be assessed separately independent of the presence of other nodules., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To meta-analyze complication rate in computed tomography (CT)-guided transthoracic lung biopsy and associated risk factors., Methods: Four databases were searched from 1/2000 to 8/2015 for studies reporting complications in CT-guided lung biopsy. Overall and major complication rates were pooled and compared between core biopsy and fine needle aspiration (FNA) using the random-effects model. Risk factors for complications in core biopsy and FNA were identified in meta-regression analysis., Results: For core biopsy, 32 articles (8,133 procedures) were included and for FNA, 17 (4,620 procedures). Pooled overall complication rates for core biopsy and FNA were 38.8 % (95 % CI: 34.3-43.5 %) and 24.0 % (95 % CI: 18.2-30.8 %), respectively. Major complication rates were 5.7 % (95 % CI: 4.4-7.4 %) and 4.4 % (95 % CI: 2.7-7.0 %), respectively. Overall complication rate was higher for core biopsy compared to FNA (p < 0.001). For FNA, larger needle diameter was a risk factor for overall complications, and increased traversed lung parenchyma and smaller lesion size were risk factors for major complications. For core biopsy, no significant risk factors were identified., Conclusions: In CT-guided lung biopsy, minor complications were common and occurred more often in core biopsy than FNA. Major complication rate was low. For FNA, smaller nodule diameter, larger needle diameter and increased traversed lung parenchyma were risk factors for complications., Key Points: • Minor complications are common in CT-guided lung biopsy • Major complication rate is low in CT-guided lung biopsy • CT-guided lung biopsy complications occur more often in core biopsy than FNA • Major complication rate is similar in core biopsy and FNA • Risk factors for FNA are larger needle diameter, smaller lesion size.

Background: US guidelines now recommend lung cancer screening with low-dose CT for high-risk individuals. Reports of new nodules after baseline screening have been scarce and are inconsistent because of differences in definitions used. We aimed to identify the occurrence of new solid nodules and their probability of being lung cancer at incidence screening rounds in the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON)., Methods: In the ongoing, multicentre, randomised controlled NELSON trial, between Dec 23, 2003, and July 6, 2006, 15 822 participants who had smoked at least 15 cigarettes a day for more than 25 years or ten cigarettes a day for more than 30 years and were current smokers, or had quit smoking less than 10 years ago, were enrolled and randomly assigned to receive either screening with low-dose CT (n=7915) or no screening (n=7907). From Jan 28, 2004, to Dec 18, 2006, 7557 individuals underwent baseline screening with low-dose CT; 7295 participants underwent second and third screening rounds. We included all participants with solid non-calcified nodules, registered by the NELSON radiologists as new or smaller than 15 mm(3) (study detection limit) at previous screens. Nodule volume was generated semiautomatically by software. We calculated the maximum volume doubling time for nodules with an estimated percentage volume change of 25% or more, representing the minimum growth rate for the time since the previous scan. Lung cancer diagnosis was based on histology, and benignity was based on histology or stable size for at least 2 years. The NELSON trial is registered at trialregister.nl, number ISRCTN63545820., Findings: We analysed data for participants with at least one solid non-calcified nodule at the second or third screening round. In the two incidence screening rounds, the NELSON radiologists registered 1222 new solid nodules in 787 (11%) participants. A new solid nodule was lung cancer in 49 (6%) participants with new solid nodules and, in total, 50 lung cancers were found, representing 4% of all new solid nodules. 34 (68%) lung cancers were diagnosed at stage I. Nodule volume had a high discriminatory power (area under the receiver operating curve 0·795 [95% CI 0·728-0·862]; p<0·0001). Nodules smaller than 27 mm(3) had a low probability of lung cancer (two [0·5%] of 417 nodules; lung cancer probability 0·5% [95% CI 0·0-1·9]), nodules with a volume of 27 mm(3) up to 206 mm(3) had an intermediate probability (17 [3·1%] of 542 nodules; lung cancer probability 3·1% [1·9-5·0]), and nodules of 206 mm(3) or greater had a high probability (29 [16·9%] of 172 nodules; lung cancer probability 16·9% [12·0-23·2]). A volume cutoff value of 27 mm(3) or greater had more than 95% sensitivity for lung cancer., Interpretation: Our study shows that new solid nodules are detected at each screening round in 5-7% of individuals who undergo screening for lung cancer with low-dose CT. These new nodules have a high probability of malignancy even at a small size. These findings should be considered in future screening guidelines, and new solid nodules should be followed up more aggressively than nodules detected at baseline screening., Funding: Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds Kankerbestrijding., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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 <100 mm(3) or diameter <5 mm) are not predictive for lung cancer. Immediate diagnostic evaluation is necessary for large nodules (≥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., Funding: Zorgonderzoek Nederland Medische Wetenschappen and Koningin Wilhelmina Fonds., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Early diagnosis of lung cancer in a treatable stage is the main purpose of lung cancer screening by computed tomography (CT). Accurate three-dimensional size and growth measurements are essential to assess the risk of malignancy. Nodule volumes can be calculated by using semi-automated volumetric software. Systematic differences in volume measurements between packages could influence nodule categorization and management decisions., Purpose: To compare volumetric measurements of solid pulmonary nodules on baseline and follow-up CT scans as well as the volume doubling time (VDT) for three software packages., Material and Methods: From a Lung Cancer Screening study (NELSON), 50 participants were randomly selected from the baseline round. The study population comprised participants with at least one pulmonary nodule at the baseline and consecutive CT examination. The volume of each nodule was determined for both time points using three semi-automated software packages (P1, P2, and P3). Manual modification was performed when automated assessment was visually inaccurate. VDT was calculated to evaluate nodule growth. Volume, VDT, and nodule management were compared for the three software packages, using P1 as the reference standard., Results: In 25 participants, 147 nodules were present on both examinations (volume: 12.0-436.6 mm(3)). Initial segmentation at baseline was evaluated to be satisfactory in 93.9% of nodules for P1, 84.4 % for P2, and 88.4% for P3. Significant difference was found in measured volume between P1 and the other two packages (P < 0.001). P2 overestimated the volume by 38 ± 24%, and P3 by 50 ± 22%. At baseline, there was consensus on nodule size categorization in 80% for P1&P2 and 74% for P1&P3. At follow-up, consensus on VDT categorization was present in 47% for P1&P2 and 44% for P1&P3., Conclusion: Software packages for lung nodule evaluation yield significant differences in volumetric measurements and VDT. This variation affects the classification of lung nodules, especially in follow-up examinations., (© The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: To retrospectively identify features that allow prediction of the disappearance of solid, indeterminate, intraparenchymal nodules detected at baseline computed tomographic (CT) screening of individuals at high risk for lung cancer., Materials and Methods: The study was institutional review board approved. Participants gave informed consent. Participants with at least one noncalcified, solid, indeterminate, intraparenchymal nodule (volume range, 50-500 mm(3)) at baseline were included (964 nodules in 750 participants). According to protocol, indeterminate nodules were re-examined at a 3-month follow-up CT examination. Repeat screening was performed at years 2 and 4. A nodule was defined as resolving if it did not appear at a subsequent CT examination. Nodule resolution was regarded as spontaneous, not the effect of treatment. CT features of resolving and nonresolving (stable and malignant) nodules were compared by means of generalized estimating equations analysis., Results: At subsequent screening, 10.1% (97 of 964) of the nodules had disappeared, 77.3% (n = 75) of these at the 3-month follow-up CT and 94.8% (n = 92) at the second round of screening. Nonperipheral nodules were more likely to resolve than were peripheral nodules (odds ratio: 3.16; 95% confidence interval: 1.76, 5.70). Compared with smooth nodules, nodules with spiculated margins showed the highest probability of disappearance (odds ratio: 4.36; 95% confidence interval: 2.24, 8.49)., Conclusion: Approximately 10% of solid, intermediate-sized, intraparenchymal pulmonary nodules found at baseline screening for lung cancer resolved during follow-up, three-quarters of which had disappeared at the 3-month follow-up CT examination. Resolving pulmonary nodules share CT features with malignant nodules., (RSNA, 2013)

Purpose: Coronary artery calcium score, traditionally based on electrocardiography (ECG)-triggered computed tomography (CT), predicts cardiovascular risk. However, nontriggered CT is extensively utilized. The study-purpose is to evaluate the in vitro agreement in coronary calcium score between nontriggered thoracic CT and ECG-triggered cardiac CT., Methods: Three artificial coronary arteries containing calcifications of different densities (high, medium, and low), and sizes (large, medium, and small), were studied in a moving cardiac phantom. Two 64-detector CT systems were used. The phantom moved at 0-90 mm∕s in nontriggered low-dose CT as index test, and at 0-30 mm∕s in ECG-triggered CT as reference. Differences in calcium scores between nontriggered and ECG-triggered CT were analyzed by t-test and 95% confidence interval. The sensitivity to detect calcification was calculated as the percentage of positive calcium scores., Results: Overall, calcium scores in nontriggered CT were not significantly different to those in ECG-triggered CT (p>0.05). Calcium scores in nontriggered CT were within the 95% confidence interval of calcium scores in ECG-triggered CT, except predominantly at higher velocities (≥50 mm∕s) for the high-density and large-size calcifications. The sensitivity for a nonzero calcium score was 100% for large calcifications, but 46%±11% for small calcifications in nontriggered CT., Conclusions: When performing multiple measurements, good agreement in positive calcium scores is found between nontriggered thoracic and ECG-triggered cardiac CT. Agreement decreases with increasing coronary velocity. From this phantom study, it can be concluded that a high calcium score can be detected by nontriggered CT, and thus, that nontriggered CT likely can identify individuals at high risk of cardiovascular disease. On the other hand, a zero calcium score in nontriggered CT does not reliably exclude coronary calcification.

Background: Coronary calcium score (CS), traditionally based on electrocardiography-triggered computed tomography (CT), predicts cardiovascular risk. Currently, nontriggered thoracic CT is extensively used, such as in lung cancer screening. The purpose of the study was to determine the correlation in CS between nontriggered and electrocardiography-triggered CT, and to evaluate the prognostic performance of the CS derived from nontriggered CT., Methods and Results: PubMed, Embase, and Web of Knowledge were searched until November 2012. Two reviewers independently screened 2120 records to identify studies reporting the CS in nontriggered CT and extracted information. Study quality was evaluated by standardized assessment tools. Cohen κ was extracted for agreement of CS categories between nontriggered and electrocardiography-triggered CT (validation). Hazard ratio (HR) was extracted for prognostic performance. Five studies about validation comprising 1316 individuals were included. Five studies about prognosis comprising 34 028 cardiac asymptomatic individuals, mainly from lung cancer screening trials, were included. All studies were of high quality. Meta-analysis could only be performed for validation studies because studies on prognostic performance were highly heterogeneous. Pooled Cohen κ for agreement between the 2 techniques was 0.89 (95% confidence interval, 0.83-0.95) for increasing CS categories. Increasing CS categories were associated with increasing risk of cardiovascular death or events. Nontriggered CT yielded false-negative CS in 8.8% of individuals and underestimated high CS in 19.1% of individuals., Conclusions: Our analysis shows the prognostic value and potential role of nontriggered assessment of coronary calcium, but it does not suggest that electrocardiography-triggered CT should be replaced by nontriggered examinations.

Objective: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals., Methods: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm(3)), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference., Results: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days., Conclusion: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals., Key Points: • Lung nodules are common in CT lung cancer screening, most being benign • Short-term follow-up CT can identify fast-growing intermediate-size lung nodules • Most fast-growing nodules on short-term follow-up CT still prove to be benign • A new volume-doubling time (VDT) cut-off is proposed for lung screening • The optimised VDT cutoff may decrease false-positive case referrals for lung cancer.

Objective: To assess the sensitivity of detection and accuracy of volumetry by manual and semi-automated quantification of artificial pulmonary nodules in an anthropomorphic thoracic phantom on low-dose CT., Methods: Fifteen artificial spherical nodules (diameter 3, 5, 8, 10 and 12 mm; CT densities -800, -630 and +100 HU) were randomly placed inside an anthropomorphic thoracic phantom. The phantom was examined on 16- and 64-row multidetector CT with a low-dose protocol. Two independent blinded observers screened for pulmonary nodules. Nodule diameter was measured manually, and volume calculated. For solid nodules (+100 HU), diameter and volume were also evaluated by semi-automated software. Differences in observed volumes between the manual and semi-automated method were evaluated by a t-test., Results: Sensitivity was 100 % for all nodules of >5 mm and larger, 60-80 % for solid and 0-20 % for non-solid 3-mm nodules. No false-positive nodules but high inter-observer reliability and inter-technique correlation were found. Volume was underestimated manually by 24.1 ± 14.0 % for nodules of any density, and 26.4 ± 15.5 % for solid nodules, compared with 7.6 ± 8.5 % (P < 0.01) semi-automatically., Conclusion: In an anthropomorphic phantom study, the sensitivity of detection is 100 % for nodules of >5 mm in diameter. Semi-automated volumetry yielded more accurate nodule volumes than manual measurements.

Objectives: A systematic review and meta-analysis to assess sensitivity and specificity of coronary CT angiography (CCTA) for significant stenosis at different degrees of coronary calcification., Methods: A literature search was performed including studies describing test characteristics of CCTA for significant stenosis, performed with at least 16-MDCT and according to calcium score (CS). Invasive coronary angiography was the reference standard. Pooled sensitivity and specificity of CCTA by CS categories and CT equipment were calculated., Results: Of 14,121 articles, 51 studies reported on the impact of calcium scoring on diagnostic performance of CCTA and could be included in the systematic review. Twenty-seven of these studies (5,203 participants) were suitable for meta-analysis. On a patient-basis, sensitivity of CCTA for significant stenosis was 95.8, 95.6, 97.6 and 99.0% for CS 0-100, 101-400, 401-1,000 and >1,000 respectively. Specificity was 91.2, 88.2, 50.6 and 84.0% respectively. Specificity of CCTA was significantly lower for CS 401-1,000 due to lack of patients without significant stenosis. Sensitivity and specificity of 16-MDCT were significantly lower compared to more modern CT systems., Conclusions: Even in cases of severe coronary calcification, sensitivity and specificity of CCTA for significant stenosis are high. With 64-MDCT and newer CT systems, a CS cut-off for performing CCTA no longer seems indicated., Key Points: Decisions about performing coronary CT angiography (CCTA) sometimes depend on calcium scoring. CCTA is highly sensitive for coronary stenosis. With 16-MDCT, however, heavy calcification reduces specificity for significant stenosis. For 64-MDCT (and above), CCTA has high specificity, even with severe coronary calcification.

Objective: To evaluate performance of computer-aided detection (CAD) beyond double reading for pulmonary nodules on low-dose computed tomography (CT) by nodule volume., Methods: A total of 400 low-dose chest CT examinations were randomly selected from the NELSON lung cancer screening trial. CTs were evaluated by two independent readers and processed by CAD. A total of 1,667 findings marked by readers and/or CAD were evaluated by a consensus panel of expert chest radiologists. Performance was evaluated by calculating sensitivity of pulmonary nodule detection and number of false positives, by nodule characteristics and volume., Results: According to the screening protocol, 90.9 % of the findings could be excluded from further evaluation, 49.2 % being small nodules (less than 50 mm(3)). Excluding small nodules reduced false-positive detections by CAD from 3.7 to 1.9 per examination. Of 151 findings that needed further evaluation, 33 (21.9 %) were detected by CAD only, one of them being diagnosed as lung cancer the following year. The sensitivity of nodule detection was 78.1 % for double reading and 96.7 % for CAD. A total of 69.7 % of nodules undetected by readers were attached nodules of which 78.3 % were vessel-attached., Conclusions: CAD is valuable in lung cancer screening to improve sensitivity of pulmonary nodule detection beyond double reading, at a low false-positive rate when excluding small nodules., Key Points: • Computer-aided detection (CAD) has known advantages for computed tomography (CT). • Combined CAD/nodule size cut-off parameters assist CT lung cancer screening. • This combination improves the sensitivity of pulmonary nodule detection by CT. • It increases the positive predictive value for cancer detection.

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 < .01) more nodules. The sensitivity, specificity, PPV, and NPV were 95.9% (71 of 74), 80.2% (6001 of 7483), 4.6% (71 of 1553) and 99.9% (6001 of 6004) for single reading and 98.6% (73 of 74), 80.0% (1497 of 7483), 4.6% (73 of 1570), and 99.9% (5986 of 5987) for consensus double reading, respectively., 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., (© RSNA, 2011.)

Objective: To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings., Methods: The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume., Results: The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P = 0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement., Conclusion: A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies.

Background: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT., Methods: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more., Results: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up., Conclusions: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.), (2009 Massachusetts Medical Society)

The purpose of the study was to assess the reliability of (semi-) automatic left ventricular (LV) function measurements using three different software packages on the same dual-source computed tomography (DSCT) datasets and to compare agreement among the software packages. Forty consecutive patients, undergoing cardiac DSCT were included (31 men, mean age 58±14 years). LV function analysis was performed with all three software packages. ANOVA testing was used to determine the difference among the repeated measurements and the difference among the software packages. Bland-Altman plots were computed to describe the agreement among the software packages. No significant difference was found among the repeated measurements. In the comparison of the three software packages, a significant difference was observed when measurements were used with minimal user interaction. When end-diastolic and end-systolic phases were manually set, there was no overall significant difference, but in 12.5% of patients a large (>10%) difference in LVEF was found. All three software packages have good intraobserver variability, but the results of the three packages were significantly different. For clinical use, one should be aware of the clinical impact of possible segmentation flaws when (semi-)automatic LV function assessment is used.

Purpose: To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules., Materials and Methods: Solid indeterminate nodules between 50 and 500 mm(3) (4.6-9.8mm) were assessed at 3 and 12 months after baseline lung cancer screening (NELSON study). Nodules were classified based on morphology (spherical or non-spherical), shape (round, polygonal or irregular) and margin (smooth, lobulated, spiculated or irregular). The mean CT density of the nodule was automatically generated in Hounsfield units (HU) by the Lungcare software., Results: From April 2004 to July 2006, 7310 participants underwent baseline screening. In 312 participants 372 solid purely intra-parenchymal nodules were found. Of them, 16 (4%) were malignant. Benign nodules were 82.8mm(3) (5.4mm) and malignant nodules 274.5mm(3) (8.1mm) (p=0.000). Baseline CT density for benign nodules was 42.7 HU and for malignant nodules -2.2 HU (p=ns). The median change in density for benign nodules was -0.1 HU and for malignant nodules 12.8 HU (p<0.05). Compared to benign nodules, malignant nodules were more often non-spherical, irregular, lobulated or spiculated at baseline, 3-month and 1-year follow-up (p<0.0001). In the majority of the benign and malignant nodules there was no change in morphology, shape and margin during 1 year of follow-up (p=ns)., Conclusion: Baseline nodule density and changes in nodule features cannot be used to discriminate between benign and malignant solid indeterminate pulmonary nodules, but an increase in density is suggestive for malignancy and requires a shorter follow-up or a biopsy.

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 (>50mm3) 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 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50-5486mm3). 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 50mm3, 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.

The objective of our study was the determination of the influence of the sequential and spiral acquisition modes on the concordance and deviation of the calcium score on 64-slice multi-detector computed tomography (MDCT) scanners in comparison to electron beam tomography (EBT) as the gold standard. Our methods and materials were an anthropomorphic cardio CT phantom with different calcium inserts scanned in sequential and spiral acquisition modes on three identical 64-slice MDCT scanners of manufacturer A and on three identical 64-slice MDCT scanners of manufacturer B and on an EBT system. Every scan was repeated 30 times with and 15 times without a small random variation in the phantom position for both sequential and spiral modes. Significant differences were observed between EBT and 64-slice MDCT data for all inserts, both acquisition modes, and both manufacturers of MDCT systems. High regression coefficients (0.90-0.98) were found between the EBT and 64-slice MDCT data for both scoring methods and both systems with high correlation coefficients (R2>0.94). System A showed more significant differences between spiral and sequential mode than system B. Almost no differences were observed in scanners of the same manufacturer for the Agatston score and no differences for the Volume score. The deviations of the Agatston and Volume scores showed regression dependencies approximately equal to the square root of the absolute score. The Agatston and Volume scores obtained with 64-slice MDCT imaging are highly correlated with EBT-obtained scores but are significantly underestimated (-10% to -2%) for both sequential and spiral acquisition modes. System B is more independent of acquisition mode to calcium score than system A. The Volume score shows no intramanufacturer dependency and its use is advocated versus the Agatston score. Using the same cut points for MDCT-based calcium scores as for EBT-based calcium scores can result in classifying individuals into a too low risk category. System information and scanprotocol is therefore needed for every calcium score procedure to ensure a correct clinical interpretation of the obtained calcium score results.

The aim of this meta-analysis was to calculate the sensitivity of contrast-enhanced multi-detector computed tomography (MDCT) compared with coronary angiography (CAG) in incident patients suspected of coronary artery disease (CAD). We searched PubMed, Embase, bibliographies of original papers and reviews to identify original papers including > or =20 patients. Two independent reviewers selected papers and judged eligible papers on quality. Heterogeneity was assessed and homogeneous subgroups were pooled. Of the 15 included studies, ten provided moderately homogeneous patient-based analyses with absolute diagnostic numbers (n = 630 patients). Pooled sensitivity was 89% (95% confidence interval: 85-92%). Scanners with 16 detectors (n = 4) had higher sensitivities (pooled sensitivity: 91%) than four-detector scanners (n = 6; pooling not possible due to heterogeneity). Seven studies reported sensitivity for a proximal stenosis, but different definitions were used making pooling impossible; sensitivities ranged from 75 to 100%. The sensitivity of four- and 16-detector MDCT is not sufficient to rule out any stenosis in patients suspected of CAD. No conclusions can be drawn with respect to the sensitivity for clinically relevant or proximal stenoses.