Feasibility of cardiovascular population-based CT screening

The prevalence of cardiovascular disease (CVD) is high in The Netherlands, with annual incidence of 123,200 (only coronary heart disease). There is an urgent need for large-scale population-based randomized-controlled trials showing the impact of CVD screening followed by treatment in high risk individuals according to their CVD risk based on classical factors and/or based on coronary calcium quantified with CT. The goal of CVD CT screening is to determine the amount of coronary calcium of an individual and to stratify individuals with high levels of coronary calcium and to reduce the morbidity and mortality by offering these individuals treatment at an early stage to stop or delay progression of subclinical CVD. One of the challenges in CVD CT screening is to secure the validity of coronary calcium quantification to perform proper risk stratification on one hand, while screening large populations at a radiation dose as-low-as-possible on the other hand.The results described in this thesis show that cardiovascular population-based CT screening is feasible with a standardized and validated imaging biomarker (in this case coronary calcium) protocol. This protocol was applied in the ROBINSCA trial in which 13,000 participants were screened. Combining screening protocols, optimizing scan parameters and using latest generation of dual-source CT can significantly reduce the radiation dose. An imaging biomarker profile including quality control guidelines for coronary calcium is needed to ensure proper use of dose-reduced protocols in population-based screening in the future

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 postprocessing of CT images are provided. Finally, future perspectives and recommendations are provided for lung cancer screening CT protocols

Coronary artery calcium scoring in individuals at risk for coronary artery disease:current status and future perspectives

The aim of this review is to provide clinicians with an overview of the role of coronary artery calcium (CAC) scoring across the spectrum ranging from asymptomatic individuals to chronic chest pain patients. We will briefly introduce the technical background of CAC scoring, summarize the major guidelines per type of patient at risk and discuss latest research with respect to CAC. Finally, the reader should be able to determine when CAC scoring is indicated or may be of added value

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

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

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

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

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