Lung cancer screening.

Randomised controlled trials, including the National Lung Screening Trial (NLST) and the NELSON trial, have shown reduced mortality with lung cancer screening with low-dose CT compared with chest radiography or no screening. Although research has provided clarity on key issues of lung cancer screening, uncertainty remains about aspects that might be critical to optimise clinical effectiveness and cost-effectiveness. This Review brings together current evidence on lung cancer screening, including an overview of clinical trials, considerations regarding the identification of individuals who benefit from lung cancer screening, management of screen-detected findings, smoking cessation interventions, cost-effectiveness, the role of artificial intelligence and biomarkers, and current challenges, solutions, and opportunities surrounding the implementation of lung cancer screening programmes from an international perspective. Further research into risk models for patient selection, personalised screening intervals, novel biomarkers, integrated cardiovascular disease and chronic obstructive pulmonary disease assessments, smoking cessation interventions, and artificial intelligence for lung nodule detection and risk stratification are key opportunities to increase the efficiency of lung cancer screening and ensure equity of access.

Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population.

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 mm3 or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm3), clinically relevant lung nodules (≥100 mm3), and actionable nodules (≥300 mm3) 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.

CT Myocardial Perfusion and CT-FFR versus Invasive FFR for Hemodynamic Relevance of Coronary Artery Disease.

Background CT-derived fractional flow reserve (CT-FFR) and dynamic CT myocardial perfusion imaging enhance the specificity of coronary CT angiography (CCTA) for ruling out coronary artery disease (CAD). However, evidence on comparative diagnostic value remains scarce. Purpose To compare the diagnostic accuracy of CCTA plus CT-FFR, CCTA plus CT perfusion, and sequential CCTA plus CT-FFR and CT perfusion for detecting hemodynamically relevant CAD with that of invasive angiography. Materials and Methods This secondary analysis of a prospective study included patients with chest pain referred for invasive coronary angiography at nine centers from July 2016 to September 2019. CCTA and CT perfusion were performed with third-generation dual-source CT scanners. CT-FFR was assessed on-site. Independent core laboratories analyzed CCTA alone, CCTA plus CT perfusion, CCTA plus CT-FFR, and a sequential approach involving CCTA plus CT-FFR and CT perfusion for the presence of hemodynamically relevant stenosis. Invasive coronary angiography with invasive fractional flow reserve was the reference standard. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve (AUC) were compared with the Sign test and DeLong test. Results Of the 105 participants (mean age, 64 years ± 8 [SD]; 68 male), 49 (47%) had hemodynamically relevant stenoses at invasive coronary angiography. CCTA plus CT-FFR and CCTA plus CT perfusion showed no evidence of a difference for participant-based sensitivities (90% vs 90%, P > .99), specificities (77% vs 79%, P > .99) and vessel-based AUCs (0.84 [95% CI: 0.77, 0.91] vs 0.83 [95% CI: 0.75, 0.91], P = .90). Both had higher participant-based specificity than CCTA alone (54%, both P < .001) without evidence of a difference in sensitivity between CCTA (94%) and CCTA plus CT perfusion (P = .50) or CCTA plus CT-FFR (P = .63). The sequential approach combining CCTA plus CT-FFR with CT perfusion achieved higher participant-based specificity than CCTA plus CT-FFR (88% vs 77%, P = .03) without evidence of a difference in participant-based sensitivity (88% vs 90%, P > .99) and vessel-based AUC (0.85 [95% CI: 0.77, 0.93], P = .78). Compared with CCTA plus CT perfusion, the sequential approach showed no evidence of a difference in participant-based sensitivity (P > .99), specificity (P = .06), or vessel-based AUC (P = .54). Conclusion There was no evidence of a difference in diagnostic accuracy between CCTA plus CT-FFR and CCTA plus CT perfusion for detecting hemodynamically relevant CAD. A sequential approach combining CCTA plus CT-FFR with CT perfusion led to improved participant-based specificity with no evidence of a difference in sensitivity compared with CCTA plus CT-FFR. ClinicalTrials.gov registration no.: NCT02810795 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Low-Dose CT-derived Bronchial Parameters in Individuals with Healthy Lungs.

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 [ß] range = 3.49-3.66 mm; LA, ß range = 25.40-29.76 mm2; WT, ß range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT (r2 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.

Lung Nodule Management in Low-Dose CT Screening for Lung Cancer: Lessons from the NELSON Trial.

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.

Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach.

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 mm3) and 2) a clinically relevant lung nodule (volume ≥100 mm3). 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.

Performance of Lung-RADS in different target populations: a systematic review and meta-analysis.

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.

Enhancing a deep learning model for pulmonary nodule malignancy risk estimation in chest CT with uncertainty estimation.

OBJECTIVE: To investigate the effect of uncertainty estimation on the performance of a Deep Learning (DL) algorithm for estimating malignancy risk of pulmonary nodules. METHODS AND MATERIALS: In this retrospective study, we integrated an uncertainty estimation method into a previously developed DL algorithm for nodule malignancy risk estimation. Uncertainty thresholds were developed using CT data from the Danish Lung Cancer Screening Trial (DLCST), containing 883 nodules (65 malignant) collected between 2004 and 2010. We used thresholds on the 90th and 95th percentiles of the uncertainty score distribution to categorize nodules into certain and uncertain groups. External validation was performed on clinical CT data from a tertiary academic center containing 374 nodules (207 malignant) collected between 2004 and 2012. DL performance was measured using area under the ROC curve (AUC) for the full set of nodules, for the certain cases and for the uncertain cases. Additionally, nodule characteristics were compared to identify trends for inducing uncertainty. RESULTS: The DL algorithm performed significantly worse in the uncertain group compared to the certain group of DLCST (AUC 0.62 (95% CI: 0.49, 0.76) vs 0.93 (95% CI: 0.88, 0.97); p < .001) and the clinical dataset (AUC 0.62 (95% CI: 0.50, 0.73) vs 0.90 (95% CI: 0.86, 0.94); p < .001). The uncertain group included larger benign nodules as well as more part-solid and non-solid nodules than the certain group. CONCLUSION: The integrated uncertainty estimation showed excellent performance for identifying uncertain cases in which the DL-based nodule malignancy risk estimation algorithm had significantly worse performance. CLINICAL RELEVANCE STATEMENT: Deep Learning algorithms often lack the ability to gauge and communicate uncertainty. For safe clinical implementation, uncertainty estimation is of pivotal importance to identify cases where the deep learning algorithm harbors doubt in its prediction. KEY POINTS: • Deep learning (DL) algorithms often lack uncertainty estimation, which potentially reduce the risk of errors and improve safety during clinical adoption of the DL algorithm. • Uncertainty estimation identifies pulmonary nodules in which the discriminative performance of the DL algorithm is significantly worse. • Uncertainty estimation can further enhance the benefits of the DL algorithm and improve its safety and trustworthiness.

Reference formulas for chest CT-derived lobar volumes in the lung-healthy general population.

INTRODUCTION: Lung hyperinflation, a key contributor to dyspnea in chronic obstructive pulmonary disease (COPD), can be quantified via chest computed tomography (CT). Establishing reference equations for lobar volumes and total lung volume (TLV) can aid in evaluating lobar hyperinflation, especially for targeted lung volume reduction therapies. METHODS: The Imaging in Lifelines study (ImaLife) comprises 11,729 participants aged 45 and above with analyzed inspiratory low-dose thoracic CT scans. Lung and lobar volumes were measured using an automatic AI-based segmentation algorithm (LungSeg). For the main analysis, participants were excluded if they had self-reported COPD/asthma, lung disease on CT, airflow obstruction on lung function testing, were currently smoking, aged over 80 years, or had height outside the 99% confidence interval. Reference equations for TLV and lobar volumes were determined using linear regression considering age and height, stratified by sex. For the subanalysis, participants who were currently smoking or experiencing airflow obstruction were compared to the group of the main analysis. RESULTS: The study included 7306 lung-healthy participants, 97.5% Caucasian, 43.6% men, with mean age of 60.3 ± 9.5 years. Lung and lobar volumes generally increased with age and height. Men consistently had higher volumes than women when adjusted for height. R2 values ranged from 7.8 to 19.9%. In smokers and those with airway obstruction, volumes were larger than in lung-healthy groups, with the largest increases measured in the upper lobes. CONCLUSION: The established reference equations for CT-derived TLV and lobar volumes provide a standardized interpretation for individuals aged 45 to 80 of Northern European descent. KEY POINTS: Question Lobar lung volumes can be derived from inspiratory CT scans, but healthy-lung reference values are lacking. Findings Lung and lobar volumes generally increased with age and height. Reference equations for lung/lobar volumes were derived from a sizeable lung-healthy population. Clinical relevance This study provides reference equations for inspiratory CT-derived lung and lobar volumes in a lung-healthy population, potentially useful for assessing candidates for lung volume reduction therapies, for lobe removal in lung cancer patients, and in case of restrictive pulmonary diseases.

ESR Essentials: imaging in stable chest pain - practice recommendations by ESCR.

Stable chest pain is a common symptom with multiple potential causes. Non-invasive imaging has an important role in diagnosis and guiding management through the assessment of coronary stenoses, atherosclerotic plaque, myocardial ischaemia or infarction, and cardiac function. Computed tomography (CT) provides the anatomical evaluation of coronary artery disease (CAD) with the assessment of stenosis, plaque type and plaque burden, with additional functional information available from CT fractional flow reserve (FFR) or CT myocardial perfusion imaging. Stress magnetic resonance imaging, nuclear stress myocardial perfusion imaging, and stress echocardiography can assess myocardial ischaemia and other cardiac functional parameters. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing may be considered for patients with known CAD, where the clinical significance is uncertain based on anatomical testing, or in patients with high pre-test probability. This practice recommendations document can be used to guide the selection of non-invasive imaging for patients with stable chest pain and provides brief recommendations on how to perform and report these diagnostic tests. KEY POINTS: The selection of non-invasive imaging tests for patients with stable chest pain should be based on symptoms, pre-test probability, and previous history. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. KEY RECOMMENDATIONS: Non-invasive imaging is an important part of the assessment of patients with stable chest pain. The selection of non-invasive imaging test should be based on symptoms, pre-test probability, and previous history. (Level of evidence: High). Coronary CT angiography can be used as a first line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. CT provides information on stenoses, plaque type, plaque volume, and if required functional information with CT fractional flow reserve or CT perfusion. (Level of evidence: High). Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. Stress MRI, SPECT, PET, and echocardiography can provide information on myocardial ischemia, along with cardiac functional and other information. (Level of evidence: Medium).

Competence of radiologists in cardiac CT and MR imaging in Europe: insights from the ESCR Registry.

RATIONALE: To provide an overview of the current status of cardiac multimodality imaging practices in Europe and radiologist involvement using data from the European Society of Cardiovascular Radiology (ESCR) MRCT-registry. MATERIALS AND METHODS: Numbers on cardiac CT and MRI examinations were extracted from the MRCT-registry of the ESCR, entered between January 2011 and October 2023 (n = 432,265). Data collection included the total/annual numbers of examinations, indications, complications, and reporting habits. RESULTS: Thirty-two countries contributed to the MRCT-registry, including 29 European countries. Between 2011 and 2022, there was a 4.5-fold increase in annually submitted CT examinations, from 3368 to 15,267, and a 3.8-fold increase in MRI examinations, from 3445 to 13,183. The main indications for cardiac CT were suspected coronary artery disease (CAD) (59%) and transcatheter aortic valve replacement planning (21%). The number of patients with intermediate pretest probability who underwent CT for suspected CAD showed an increase from 61% in 2012 to 82% in 2022. The main MRI indications were suspected myocarditis (26%), CAD (21%), and suspected cardiomyopathy (19%). Adverse event rates were very low for CT (0.3%) and MRI (0.7%) examinations. Reporting of CT and MRI examinations was performed mainly by radiologists (respectively 76% and 71%) and, to a lesser degree, in consensus with non-radiologists (19% and 27%, respectively). The remaining examinations (4.9% CT and 1.7% MRI) were reported by non-radiological specialties or in separate readings of radiologists and non-radiologists. CONCLUSIONS: Real-life data on cardiac imaging in Europe using the largest available MRCT-registry demonstrate a considerable increase in examinations over the past years, the vast majority of which are read by radiologists. These findings indicate that radiologists contribute to meeting the increasing demands of competent and effective care in cardiac imaging to a relevant extent. CLINICAL RELEVANCE STATEMENT: The number of cardiac CT and MRI examinations has risen over the past years, and radiologists read the vast majority of these studies as recorded in the MRCT-registry. KEY POINTS: • The number of cardiac imaging examinations is constantly increasing. • Radiologists play a central role in providing cardiac CT and MR imaging services to a large volume of patients. • Cardiac CT and MR imaging examinations performed and read by radiologists show a good safety profile.

Feasibility of virtual non-iodine coronary calcium scoring on dual source photon-counting coronary CT angiography: a dynamic phantom study.

BACKGROUND: The aim of our current systematic dynamic phantom study was first, to optimize reconstruction parameters of coronary CTA (CCTA) acquired on photon counting CT (PCCT) for coronary artery calcium (CAC) scoring, and second, to assess the feasibility of calculating CAC scores from CCTA, in comparison to reference calcium scoring CT (CSCT) scans. METHODS: In this phantom study, an artificial coronary artery was translated at velocities corresponding to 0, < 60, and 60-75 beats per minute (bpm) within an anthropomorphic phantom. The density of calcifications was 100 (very low), 200 (low), 400 (medium), and 800 (high) mgHA/cm3, respectively. CCTA was reconstructed with the following parameters: virtual non-iodine (VNI), with and without iterative reconstruction (QIR level 2, QIR off, respectively); kernels Qr36 and Qr44f; slice thickness/increment 3.0/1.5 mm and 0.4/0.2 mm. The agreement in risk group classification between CACCCTA and CACCSCT scoring was measured using Cohen weighted linear κ with 95% CI. RESULTS: For CCTA reconstructed with 0.4 mm slice thickness, calcium detectability was perfect (100%). At < 60 bpm, CACCCTA of low, and medium density calcification was underestimated by 53%, and 15%, respectively. However, CACCCTA was not significantly different from CACCSCT of very low, and high-density calcifications. The best risk agreement was achieved when CCTA was reconstructed with QIR off, Qr44f, and 0.4 mm slice thickness (κ = 0.762, 95% CI 0.671-0.853). CONCLUSION: In this dynamic phantom study, the detection of calcifications with different densities was excellent with CCTA on PCCT using thin-slice VNI reconstruction. Agatston scores were underestimated compared to CSCT but agreement in risk classification was substantial. CLINICAL RELEVANCE STATEMENT: Photon counting CT may enable the implementation of coronary artery calcium scoring from coronary CTA in daily clinical practice. KEY POINTS: Photon-counting CTA allows for excellent detectability of low-density calcifications at all heart rates. Coronary artery calcium scoring from coronary CTA acquired on photon counting CT is feasible, although improvement is needed. Adoption of the standard acquisition and reconstruction protocol for calcium scoring is needed for improved quantification of coronary artery calcium to fully employ the potential of photon counting CT.

Phase angle and donor type are determinants of coronary artery calcification in stable kidney transplant recipients at twelve months after transplantation.

BACKGROUND AND AIM: Coronary artery calcification (CAC) partially explains the excess cardiovascular morbidity and mortality after kidney transplantation. This study aimed to investigate determinants of CAC in stable kidney transplant recipients at 12 months post-transplantation. METHODS AND RESULTS: CAC-score was quantified by the Agatston method using non-contrast enhanced computed tomography, and age- and sex-standardized CAC-percentiles were calculated. Univariable and multivariable multinomial logistic regression was performed to study potential determinants of CAC. The independent determinants were included in multivariable multinomial logistic regression adjusting for potential confounders. 203 KTRs (age 54.0 ± 14.7 years, 61.1% male) were included. Participants were categorized into four groups according to CAC percentiles (p = 0 [CAC-score = 0], n = 68; p ≥ 1%-p ≤ 50% [CAC score = 29.0 (4.0-166.0)], n = 31; p > 50 ≤ 75% [CAC score = 101.0 (23.8-348.3)], n = 26; and p>75% [CAC score = 581.0 (148.0-1652)], n = 83). Upon multivariable multinomial logistic regression, patients with a narrower phase angle and patients who had received a graft from a deceased donor had a higher risk of being in the >75th CAC-percentile. CONCLUSIONS: This study identifies not only metabolic and transplant-related factors, but also phase angle, a composite marker of cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. This study offers new perspectives for future research into the value of bioelectrical impedance analysis in relation to vascular calcification in kidney transplant recipients.

Computed tomography and coronary artery calcium score for screening of coronary artery disease and cardiovascular risk management in asymptomatic individuals.

Several risk prediction models exist to predict atherosclerotic cardiovascular disease in asymptomatic individuals, but systematic reviews have generally found these models to be of limited utility. The coronary artery calcium score (CACS) offers an improvement in risk prediction, yet its role remains contentious. Notably, its negative predictive value has a high ability to rule out clinically relevant atherosclerotic cardiovascular disease. Nonetheless, CACS 0 does not permanently reclassify to a lower cardiovascular risk and periodic reassessment every 5 to 10 years remains necessary. Conversely, elevated CACS (> 100 or > 75th percentile adjusted for age, sex and ethnicity) can reclassify intermediate-risk individuals to a high risk, benefiting from preventive medication. The forthcoming update to the Dutch cardiovascular risk management guideline intends to re-position CACS for cardiovascular risk assessment as such in asymptomatic individuals. Beyond CACS as a single number, several guidelines recommend coronary CT angiography (CCTA), which provides additional information about luminal stenosis and (high-risk) plaque composition, as the first choice of test in symptomatic patients and high-risk patients. Ongoing randomised studies will have to determine the value of atherosclerosis evaluation with CCTA for primary prevention in asymptomatic individuals.

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.

BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

Motion artifact removal in coronary CT angiography based on generative adversarial networks.

OBJECTIVES: Coronary motion artifacts affect the diagnostic accuracy of coronary CT angiography (CCTA), especially in the mid right coronary artery (mRCA). The purpose is to correct CCTA motion artifacts of the mRCA using a GAN (generative adversarial network). METHODS: We included 313 patients with CCTA scans, who had paired motion-affected and motion-free reference images at different R-R interval phases in the same cardiac cycle and included another 53 CCTA cases with invasive coronary angiography (ICA) comparison. Pix2pix, an image-to-image conversion GAN, was trained by the motion-affected and motion-free reference pairs to generate motion-free images from the motion-affected images. Peak signal-to-noise ratio (PSNR), structural similarity (SSIM), Dice similarity coefficient (DSC), and Hausdorff distance (HD) were calculated to evaluate the image quality of GAN-generated images. RESULTS: At the image level, the median of PSNR, SSIM, DSC, and HD of GAN-generated images were 26.1 (interquartile: 24.4-27.5), 0.860 (0.830-0.882), 0.783 (0.714-0.825), and 4.47 (3.00-4.47), respectively, significantly better than the motion-affected images (p < 0.001). At the patient level, the image quality results were similar. GAN-generated images improved the motion artifact alleviation score (4 vs. 1, p < 0.001) and overall image quality score (4 vs. 1, p < 0.001) than those of the motion-affected images. In patients with ICA comparison, GAN-generated images achieved accuracy of 81%, 85%, and 70% in identifying no, < 50%, and ≥ 50% stenosis, respectively, higher than 66%, 72%, and 68% for the motion-affected images. CONCLUSION: Generative adversarial network-generated CCTA images greatly improved the image quality and diagnostic accuracy compared to motion-affected images. KEY POINTS: • A generative adversarial network greatly reduced motion artifacts in coronary CT angiography and improved image quality. • GAN-generated images improved diagnosis accuracy of identifying no, < 50%, and ≥ 50% stenosis.

Reproducibility of a combined artificial intelligence and optimal-surface graph-cut method to automate bronchial parameter extraction.

OBJECTIVES: Computed tomography (CT)-based bronchial parameters correlate with disease status. Segmentation and measurement of the bronchial lumen and walls usually require significant manpower. We evaluate the reproducibility of a deep learning and optimal-surface graph-cut method to automatically segment the airway lumen and wall, and calculate bronchial parameters. METHODS: A deep-learning airway segmentation model was newly trained on 24 Imaging in Lifelines (ImaLife) low-dose chest CT scans. This model was combined with an optimal-surface graph-cut for airway wall segmentation. These tools were used to calculate bronchial parameters in CT scans of 188 ImaLife participants with two scans an average of 3 months apart. Bronchial parameters were compared for reproducibility assessment, assuming no change between scans. RESULTS: Of 376 CT scans, 374 (99%) were successfully measured. Segmented airway trees contained a mean of 10 generations and 250 branches. The coefficient of determination (R2) for the luminal area (LA) ranged from 0.93 at the trachea to 0.68 at the 6th generation, decreasing to 0.51 at the 8th generation. Corresponding values for Wall Area Percentage (WAP) were 0.86, 0.67, and 0.42, respectively. Bland-Altman analysis of LA and WAP per generation demonstrated mean differences close to 0; limits of agreement (LoA) were narrow for WAP and Pi10 (± 3.7% of mean) and wider for LA (± 16.4-22.8% for 2-6th generations). From the 7th generation onwards, there was a sharp decrease in reproducibility and a widening LoA. CONCLUSION: The outlined approach for automatic bronchial parameter measurement on low-dose chest CT scans is a reliable way to assess the airway tree down to the 6th generation. STATEMENT ON CLINICAL RELEVANCE: This reliable and fully automatic pipeline for bronchial parameter measurement on low-dose CT scans has potential applications in screening for early disease and clinical tasks such as virtual bronchoscopy or surgical planning, while also enabling the exploration of bronchial parameters in large datasets. KEY POINTS: • Deep learning combined with optimal-surface graph-cut provides accurate airway lumen and wall segmentations on low-dose CT scans. • Analysis of repeat scans showed that the automated tools had moderate-to-good reproducibility of bronchial measurements down to the 6th generation airway. • Automated measurement of bronchial parameters enables the assessment of large datasets with less man-hours.

Willingness to participate in combination screening for lung cancer, chronic obstructive pulmonary disease and cardiovascular disease in four European countries.

OBJECTIVES: Lung cancer screening (LCS), using low-dose computed tomography (LDCT), can be more efficient by simultaneously screening for chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), the Big-3 diseases. This study aimed to determine the willingness to participate in (combinations of) Big-3 screening in four European countries and the relative importance of amendable participation barriers. METHODS: An online cross-sectional survey aimed at (former) smokers aged 50-75 years elicited the willingness of individuals to participate in Big-3 screening and used analytical hierarchy processing (AHP) to determine the importance of participation barriers. RESULTS: Respondents were from France (n = 391), Germany (n = 338), Italy (n = 399), and the Netherlands (n = 342), and consisted of 51.2% men. The willingness to participate in screening was marginally influenced by the diseases screened for (maximum difference of 3.1%, for Big-3 screening (73.4%) vs. lung cancer and COPD screening (70.3%)) and by country (maximum difference of 3.7%, between France (68.5%) and the Netherlands (72.3%)). The largest effect on willingness to participate was personal perceived risk of lung cancer. The most important barriers were the missed cases during screening (weight 0.19) and frequency of screening (weight 0.14), while diseases screened for (weight 0.11) ranked low. CONCLUSIONS: The difference in willingness to participate in LCS showed marginal increase with inclusion of more diseases and limited variation between countries. A marginal increase in participation might result in a marginal additional benefit of Big-3 screening. The amendable participation barriers are similar to previous studies, and the new criterion, diseases screened for, is relatively unimportant. CLINICAL RELEVANCE STATEMENT: Adding diseases to combination screening modestly improves participation, driven by personal perceived risk. These findings guide program design and campaigns for lung cancer and Big-3 screening. Benefits of Big-3 screening lie in long-term health and economic impact, not participation increase. KEY POINTS: • It is unknown whether or how combination screening might affect participation. • The addition of chronic obstructive pulmonary disease and cardiovascular disease to lung cancer screening resulted in a marginal increase in willingness to participate. • The primary determinant influencing individuals' engagement in such programs is their personal perceived risk of the disease.

Cardiac radiology in Europe: status and vision by the European Society of Cardiovascular Radiology (ESCR) and the European Society of Radiology (ESR).

Cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) are routine radiological examinations for diagnosis and prognosis of cardiac disease. The expected growth in cardiac radiology in the coming years will exceed the current scanner capacity and trained workforce. The European Society of Cardiovascular Radiology (ESCR) focuses on supporting and strengthening the role of cardiac cross-sectional imaging in Europe from a multi-modality perspective. Together with the European Society of Radiology (ESR), the ESCR has taken the initiative to describe the current status of, a vision for, and the required activities in cardiac radiology to sustain, increase and optimize the quality and availability of cardiac imaging and experienced radiologists across Europe. KEY POINTS: • Providing adequate availability for performing and interpreting cardiac CT and MRI is essential, especially with expanding indications. • The radiologist has a central role in non-invasive cardiac imaging examinations which encompasses the entire process from selecting the best modality to answer the referring physician's clinical question to long-term image storage. • Optimal radiological education and training, knowledge of the imaging process, regular updating of diagnostic standards, and close collaboration with colleagues from other specialties are essential.