Ct-defined emphysema prevalence in a Chinese and Dutch general population.

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.

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.

CT-based emphysema characterization per lobe: A proof of concept.

PURPOSE: The Fleischner society criteria are global criteria to visually evaluate and classify pulmonary emphysema on CT. It may group heterogeneous disease severity within the same category, potentially obscuring clinically relevant differences in emphysema severity. This proof-of-concept study proposes to split emphysema into more categories and to assess each lobe separately, and applies this to two general population-based cohort samples to assess what information such an extension adds. METHOD: From a consecutive sample in two general population-based cohorts with low-dose chest CT, 117 participants with more than a trace of emphysema were included. Two independent readers performed an extended per-lobe classification and assessed overall severity semi-quantitatively. An emphysema sum score was determined by adding the severity score of all lobes. Inter-reader agreement was quantified with Krippendorff Alpha. RESULTS: Based on Fleischner society criteria, 69 cases had mild to severe centrilobular emphysema, and 90 cases had mild or moderate paraseptal emphysema (42 had both types of emphysema). The emphysema sum score was significantly different between mild (10.7 ± 4.3, range 2-22), moderate (20.1 ± 3.1, range: 15-24), and severe emphysema (23.6 ± 3.4, range: 17-28, p < 0.001), but ranges showed significant overlap. Inter-reader agreement for the extended classification and sum score was substantial (alpha 0.79 and 0.85, respectively). Distribution was homogenous across lobes in never-smokers, yet heterogenous in current smokers, with upper-lobe predominance. CONCLUSIONS: The proposed emphysema evaluation method adds information to the original Fleischner society classification. Individuals in the same Fleischner category have diverse emphysema sum scores, and lobar emphysema distribution differs between smoking groups.

CT characteristics of solid pulmonary nodules of never smokers versus smokers: A population-based study.

PURPOSE: Aim was to assess CT characteristics of lung nodules in never and former smokers compared to current smokers in a population-based setting. METHOD: We included individuals aged 45-60 years taking part in the ImaLife (Imaging in Lifelines) study, with at least one solid lung nodule (≥30 mm3) on low-dose chest CT. Qualitative (location, shape, margin, nodule type, attached structures) and quantitative (count, diameter, volume) nodule characteristics were evaluated. Based on Fleischner criteria, 'high risk' nodules were defined. To examine the association between smoking status and nodule CT characteristics of participants, multi-level multinomial logistic regression corrected for clustering of nodules within participants was performed, where all odds ratios (aORs) were adjusted for age and sex. RESULTS: Overall, 1,639 individuals (median age: 55.0, IQR:50.5-58.5, 50.5% men) were included, with 42.1% never smokers, 35.3% former smokers and 22.6% current smokers. A total of 3,222 solid nodules were identified; 39.7% of individuals had multiple nodules. Nodule size, location, type and attachment were similar for never compared to current smokers. The odds of nodules with an irregular shape and irregular margin was lower in never smokers (aOR:0.64, 95 %CI:0.44-0.93; aOR:0.60, 95 %CI:0.41-0.88, respectively) and former smokers (aOR:0.61, 95 %CI:0.41-0.90; aOR:0.57, 95 %CI:0.38-0.85, respectively) compared to current smokers. The odds of a detected nodule being 'high risk' was similar for never versus current smokers (never smokers: aOR = 0.90; 95% CI:0.73-1.11). CONCLUSIONS: CT-based characteristics of solid lung nodules in never and former smokers differed only slightly from current smokers. Among individuals with solid nodules, 'high-risk' nodules were equally common in never smokers and current smokers.

Association between visual emphysema and lung nodules on low-dose CT scan in a Chinese Lung Cancer Screening Program (Nelcin-B3).

OBJECTIVES: This study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT). METHODS: Baseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm3) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking. RESULTS: Emphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26-2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09-2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32-4.50 and aOR: 1.60, 95% CI: 1.23-2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44-2.61, overall p < 0.01). CONCLUSION: In a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm3) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity. KEY POINTS: • Participants with emphysema had an increased risk of having lung nodules, especially smokers. • Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category. • The risk of lung nodules increases with CLE severity.

Association between Chest CT-defined Emphysema and Lung Cancer: A Systematic Review and Meta-Analysis.

Background Given the different methods of assessing emphysema, controversy exists as to whether it is associated with lung cancer. Purpose To perform a systematic review and meta-analysis of the association between chest CT-defined emphysema and the presence of lung cancer. Materials and Methods The PubMed, Embase, and Cochrane databases were searched up to July 15, 2021, to identify studies on the association between emphysema assessed visually or quantitatively with CT and lung cancer. Associations were determined by emphysema severity (trace, mild, or moderate to severe, assessed visually and quantitatively) and subtype (centrilobular and paraseptal, assessed visually). Overall and stratified pooled odds ratios (ORs) with their 95% CIs were obtained. Results Of the 3343 screened studies, 21 studies (107 082 patients) with 26 subsets were included. The overall pooled ORs for lung cancer given the presence of emphysema were 2.3 (95% CI: 2.0, 2.6; I2 = 35%; 19 subsets) and 1.02 (95% CI: 1.01, 1.02; six subsets) per 1% increase in low attenuation area. Studies with visual (pooled OR, 2.3; 95% CI: 1.9, 2.6; I2 = 48%; 12 subsets) and quantitative (pooled OR, 2.2; 95% CI: 1.8, 2.8; I2 = 3.7%; eight subsets) assessments yielded comparable results for the dichotomous assessment. Based on six studies (1716 patients), the pooled ORs for lung cancer increased with emphysema severity and were higher for visual assessment (2.5, 3.7, and 4.5 for trace, mild, and moderate to severe, respectively) than for quantitative assessment (1.9, 2.2, and 2.5) based on point estimates. Compared with no emphysema, only centrilobular emphysema (three studies) was associated with lung cancer (pooled OR, 2.2; 95% CI: 1.5, 3.2; P < .001). Conclusion Both visual and quantitative CT assessments of emphysema were associated with a higher odds of lung cancer, which also increased with emphysema severity. Regarding subtype, only centrilobular emphysema was significantly associated with lung cancer. Clinical trial registration no. CRD42021262163 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Hunsaker in this issue.

Community-based lung cancer screening by low-dose computed tomography in China: First round results and a meta-analysis.

OBJECTIVE: To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis. METHODS: A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies. RESULTS: In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%-0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%-85.3%) and 15.2% (95 %CI: 11.8%-18.9%), respectively. CONCLUSIONS: The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.

Latest CT technologies in lung cancer screening: protocols and radiation dose reduction.

The aim of this review is to provide clinicians and technicians with an overview of the development of CT protocols in lung cancer screening. CT protocols have evolved from pre-fixed settings in early lung cancer screening studies starting in 2004 towards automatic optimized settings in current international guidelines. The acquisition protocols of large lung cancer screening studies and guidelines are summarized. Radiation dose may vary considerably between CT protocols, but has reduced gradually over the years. Ultra-low dose acquisition can be achieved by applying latest dose reduction techniques. The use of low tube current or tin-filter in combination with iterative reconstruction allow to reduce the radiation dose to a submilliSievert level. However, one should be cautious in reducing the radiation dose to ultra-low dose settings since performed studies lacked generalizability. Continuous efforts are made by international radiology organizations to streamline the CT data acquisition and image quality assurance and to keep track of new developments in CT lung cancer screening. Examples like computer-aided diagnosis and radiomic feature extraction are discussed and current limitations are outlined. Deep learning-based solutions in post-processing of CT images are provided. Finally, future perspectives and recommendations are provided for lung cancer screening CT protocols.

Coronary Artery Calcium and Cognitive Function in Dutch Adults: Cross-Sectional Results of the Population-Based ImaLife Study.

Background The aim of this study was to investigate whether increased severity of coronary artery calcium (CAC), an imaging biomarker of subclinical coronary atherosclerosis, is associated with worse cognitive function independent of cardiovascular risk factors in a large population-based Dutch cohort with broad age range. Methods and Results A cross-sectional analysis was performed in 4988 ImaLife participants (aged 45-91 years, 58.3% women) without history of cardiovascular disease. CAC scores were obtained using nonenhanced cardiac computed tomography scanning. The CogState Brief Battery was used to assess 4 cognitive domains: processing speed, attention, working memory, and visual learning based on detection task, identification task, 1-back task, and 1-card-learning task, respectively. Differences in mean scores of each cognitive domain were compared among 4 CAC categories (0, 1-99, 100-399, ≥400) using analysis of covariates to adjust for classical cardiovascular risk factors. Age-stratified analysis (45-54, 55-64, and ≥65 years) was performed to assess whether the association of CAC severity with cognitive function differed by age. Overall, higher CAC was associated with worse performance on 1-back task after adjusting for classical cardiovascular risk factors, but CAC was not associated with the other cognitive tasks. Age-stratified analyses revealed that the association of CAC severity with working memory persisted in participants aged 45 to 54 years, while in the elderly this association lost significance. Conclusions In this Dutch population of ≥45 years, increased CAC severity was associated with worse performance of working memory, independent of classical cardiovascular risk factors. The inverse relationship of CAC score categories with working memory was strongest in participants aged 45 to 54 years.

High-pitch dual-source CT for coronary artery calcium scoring: A head-to-head comparison of non-triggered chest versus triggered cardiac acquisition.

BACKGROUND: To determine the effect of low-dose, high-pitch non-electrocardiographic (ECG)-triggered chest CT on coronary artery calcium (CAC) detection, quantification and risk stratification, compared to ECG-triggered cardiac CT. METHODS: We selected 1,000 participants from the ImaLife study, 50% with coronary calcification on cardiac CT. All participants underwent non-contrast cardiac CT followed by chest CT using third-generation dual-source technology. Reconstruction settings were equal for both acquisitions. CAC scores were determined by Agatston's method, and divided dichotomously (0, >0), and into risk categories (0, 1-99, 100-399, ≥400). We investigated the influence of heart rate and body mass index (BMI) on risk reclassification. RESULTS: Positive CAC scores on cardiac CT ranged from 1 to 6926 (median 39). Compared to cardiac CT, chest CT had sensitivity of 0.96 (95%CI 0.94-0.98) and specificity of 0.99 (95%CI 0.97-0.99) for CAC detection (κ = 0.95). In participants with coronary calcification on cardiac CT, CAC score on chest CT was lower than on cardiac CT (median 30 versus 40, p˂0.001). Agreement in CAC-based risk strata was excellent (weighted κ = 0.95). Sixty-five cases (6.5%) were reclassified by one risk category in chest CT, with fifty-five (84.6%) shifting downward. Higher BMI resulted in higher reclassification rate (13% for BMI ≥30 versus 5.2% for BMI <30, p = 0.001), but there was no effect of heart rate. CONCLUSION: Low-dose, high-pitch chest CT, using third-generation dual-source technology shows almost perfect agreement with cardiac CT in CAC detection and risk stratification. However, low-dose chest CT mainly underestimates the CAC score as compared to cardiac CT, and results in inaccurate risk categorization in BMI ≥30.

Computed Tomography Screening for Early Lung Cancer, COPD and Cardiovascular Disease in Shanghai: Rationale and Design of a Population-based Comparative Study.

RATIONALE AND OBJECTIVES: To describe the rational and design of a population-based comparative study. The objective of the study is to assess the screening performance of volume-based management of CT-detected lung nodule in comparison to diameter-based management, and to improve the effectiveness of CT screening for chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), in addition to lung cancer, based on quantitative measurement of CT imaging biomarkers in a Chinese screening setting. MATERIALS AND METHODS: A population-based comparative study is being performed, including 10,000 asymptomatic participants between 40 and 74 years old from Shanghai urban population. Participants in the intervention group undergo a low-dose chest and cardiac CT scan at baseline and 1 year later, and are managed according to NELCIN-B3 protocol. Participants in the control group undergo a low-dose chest CT scan according to the routine CT protocol and are managed according to the clinical practice. Epidemiological data are collected through questionnaires. In the fourth year from baseline, the diagnosis of the three diseases will be collected. RESULTS: The unnecessary referral rate will be compared between NELCIN-B3 and standard protocol for managing early-detected lung nodules. The effectiveness of quantitative measurement of CT imaging biomarkers for early detection of lung cancer, COPD and CVD will be evaluated. CONCLUSION: We expect that the quantitative assessment of the CT imaging biomarkers will reduce the number of unnecessary referrals for early detected lung nodules, and will improve the early detection of COPD and CVD in a Chinese urban population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03988322. Registered on 14 June 2019.

Comparison of National Comprehensive Cancer Network and European Position Statement protocols for nodule management in low-dose computed tomography lung cancer screening in a general Chinese population.

BACKGROUND: Low-dose computed tomography (LDCT) lung cancer screening often refers individuals to unnecessary examinations. This study aims to compare the European Position Statement (EUPS) and National Comprehensive Cancer Network (NCCN) protocols in management of participants at baseline screening round. METHODS: LDCT lung cancer screening was prospectively performed in a Chinese asymptomatic population aged 40-74 years. A total of 1,000 consecutive baseline LDCT scans were read twice independently. All screen-detected lung nodules by the first reader were included. The first reader manually measured the diameter of lung nodules (NCCN protocol), and the second reader semi-automatically measured the volume and diameter (EUPS volume and diameter protocols). The protocols were used to classify the participants into three management groups: next screening round, short-term repeat LDCT scan and referral to a pulmonologist. Groups were compared using Wilcoxon test for paired samples. Number of lung cancers by protocols was provided. RESULTS: Of the 1,000 participants (61.4±6.7 years old), 168 lung nodules in 124 participants were visually detected and manually measured in the first reading, and re-measured semi-automatically. Applying the NCCN protocol, EUPS volume and diameter protocol, the proportion of referrals among all participants was 0.6%, 1.9%, and 1.4%, respectively. The proportion of short-term repeat scans was 4.5%, 9.7% and 4.5%, respectively. Among the 10 lung cancer patients, one would have been diagnosed earlier if the EUPS volume protocol would have been followed. CONCLUSIONS: In a first round screening in a Chinese general population, the lower threshold for referral in the EUPS protocol as compared to the NCCN protocol, leads to more referrals to a pulmonologist, with the potential of earlier cancer diagnosis. The EUPS volume protocol recommends fewer participants to short-term repeat LDCT scan than the EUPS diameter protocol. Follow-up studies should show the impact of both protocols on (interval) cancer diagnosis.

Cardiovascular Risk Factors and Coronary Calcification in a Middle-aged Dutch Population: The ImaLife Study.

PURPOSE: To assess the presence of coronary artery calcium (CAC) and its association with cardiovascular risk factors and Systematic COronary Risk Evaluation (SCORE) risk in a middle-aged Dutch population. METHODS: Classic cardiovascular risk factors and CAC were analyzed in 4083 participants aged 45 to 60 years (57.9% women) from the population-based ImaLife study. CAC scores were quantified on noncontrast cardiac CT scans. Age-specific and sex-specific distribution of CAC categories (0, 1 to 99, 100 to 299, ≥300) and percentiles were determined. SCORE risk categories (<1%, ≥1% to 5%, and ≥5%) were compared with CAC distribution. Population attributable fractions (PAFs) of classic risk factors for CAC were estimated. RESULTS: CAC was present in 54.5% male and 26.5% female participants. The percentage of individuals with CAC increased with increasing age. Mean SCORE was 2.0% in men and 0.7% in women. In SCORE <1%, 32.7% of men and 17.1% of women had CAC. In men with SCORE ≥5%, 26.9% had no CAC. Only 0.1% of women had SCORE ≥5%. PAF of classic risk factors for CAC was 18.5% in men and 31.4% in women. PAF was highest for hypertension (in men 8.0%, 95% confidence interval, 4.2%-11.8%; in women 13.1%, 95% confidence interval, 7.9%-18.2%) followed by hypercholesterolemia and obesity. CONCLUSION: In this middle-aged cohort, more than half of the men and a quarter of the women had CAC. One out of 4 men at high risk (SCORE ≥5%) could be placed into a lower risk category owing to absence of CAC. Thus, adding CAC scoring to SCORE could have considerable effect on cardiovascular risk classification. Elimination of exposure to classic risk factors could reduce limited proportion of CAC in a middle-aged population.

Deep learning-based pulmonary nodule detection: Effect of slab thickness in maximum intensity projections at the nodule candidate detection stage.

BACKGROUND AND OBJECTIVE: To investigate the effect of the slab thickness in maximum intensity projections (MIPs) on the candidate detection performance of a deep learning-based computer-aided detection (DL-CAD) system for pulmonary nodule detection in CT scans. METHODS: The public LUNA16 dataset includes 888 CT scans with 1186 nodules annotated by four radiologists. From those scans, MIP images were reconstructed with slab thicknesses of 5 to 50 mm (at 5 mm intervals) and 3 to 13 mm (at 2 mm intervals). The architecture in the nodule candidate detection part of the DL-CAD system was trained separately using MIP images with various slab thicknesses. Based on ten-fold cross-validation, the sensitivity and the F2 score were determined to evaluate the performance of using each slab thickness at the nodule candidate detection stage. The free-response receiver operating characteristic (FROC) curve was used to assess the performance of the whole DL-CAD system that took the results combined from 16 MIP slab thickness settings. RESULTS: At the nodule candidate detection stage, the combination of results from 16 MIP slab thickness settings showed a high sensitivity of 98.0% with 46 false positives (FPs) per scan. Regarding a single MIP slab thickness of 10 mm, the highest sensitivity of 90.0% with 8 FPs/scan was reached before false positive reduction. The sensitivity increased (82.8% to 90.0%) for slab thickness of 1 to 10 mm and decreased (88.7% to 76.6%) for slab thickness of 15-50 mm. The number of FPs was decreasing with increasing slab thickness, but was stable at 5 FPs/scan at a slab thickness of 30 mm or more. After false positive reduction, the DL-CAD system, utilizing 16 MIP slab thickness settings, had the sensitivity of 94.4% with 1 FP/scan. CONCLUSIONS: The utilization of multi-MIP images could improve the performance at the nodule candidate detection stage, even for the whole DL-CAD system. For a single slab thickness of 10 mm, the highest sensitivity for pulmonary nodule detection was reached at the nodule candidate detection stage, similar to the slab thickness usually applied by radiologists.

Deep learning for automated exclusion of cardiac CT examinations negative for coronary artery calcium.

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.

Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial.

AIMS: Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. METHODS AND RESULTS: Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10-20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100-399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). CONCLUSION: We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. TRIAL REGISTRATION NUMBER: NTR6471.

The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function: A Systematic Review and Meta-Analysis.

AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.