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.

The influence of motion-compensated reconstruction on coronary artery analysis for a dual-layer detector CT system: a dynamic phantom study.

OBJECTIVES: Cardiac motion artifacts hinder the assessment of coronary arteries in coronary computed tomography angiography (CCTA). We investigated the impact of motion compensation reconstruction (MCR) on motion artifacts in CCTA at various heart rates (HR) using a dynamic phantom. MATERIALS AND METHODS: An artificial hollow coronary artery (5-mm diameter lumen) filled with iodinated contrast agent (400 HU at 120 kVp), positioned centrally in an anthropomorphic chest phantom, was scanned using a dual-layer spectral detector CT. The artery was translated at constant horizontal velocities (0-80 mm/s, increment of 10 mm/s). For each velocity, five CCTA scans were repeated using a clinical protocol. Motion artifacts were quantified using the in-plane motion area. Regression analysis was performed to calculate the reduction in motion artifacts provided by MCR, by division of the slopes of non-MCR and MCR fitted lines. RESULTS: Reference mean (95% confidence interval) motion artifact area was 24.9 mm2 (23.8, 26.0). Without MCR, motion artifact areas for velocities exceeding 20 mm/s were significantly larger (up to 57.2 mm2 (40.1, 74.2)) than the reference. With MCR, no significant differences compared to the reference were shown for all velocities, except for 70 mm/s (29.0 mm2 (27.0, 31.0)). The slopes of the fitted data were 0.44 and 0.04 for standard and MCR reconstructions, respectively, resulting in an 11-time motion artifact reduction. CONCLUSION: MCR may improve CCTA assessment in patients by reducing coronary artery motion artifacts, especially in those with elevated HR who cannot receive beta blockers or do not attain the targeted HR. CLINICAL RELEVANCE STATEMENT: This vendor-specific motion compensation reconstruction may improve coronary computed tomography angiography assessment in patients by reduction of coronary artery motion artifacts, especially in those with elevated various heart rates (HR) who cannot receive beta blockers or do not attain the targeted HR. KEY POINTS: • Motion artifacts are known to hinder the assessment of coronary arteries on coronary CT angiography (CCTA), leading to more non-diagnostic scans. • This dynamic phantom study shows that motion compensation reconstruction (MCR) reduces motion artifacts at various velocities, which may help to decrease the number of non-diagnostic scans. • MCR in this study showed to reduce motion artifacts 11-fold.

Radiation dose optimization for photon-counting CT coronary artery calcium scoring for different patient sizes: a dynamic phantom study.

PURPOSE: To systematically assess the radiation dose reduction potential of coronary artery calcium (CAC) assessments with photon-counting computed tomography (PCCT) by changing the tube potential for different patient sizes with a dynamic phantom. METHODS: A hollow artery, containing three calcifications of different densities, was translated at velocities corresponding to 0, < 60, 60-75, and > 75 beats per minute within an anthropomorphic phantom. Extension rings were used to simulate average- and large -sized patients. PCCT scans were made with the reference clinical protocol (tube potential of 120 kilovolt (kV)), and with 70, 90, Sn100, Sn140, and 140 kV at identical image quality levels. All acquisitions were reconstructed at a virtual monoenergetic energy level of 70 keV. For each calcification, Agatston scores and contrast-to-noise ratios (CNR) were determined, and compared to the reference with Wilcoxon signed-rank tests, with p < 0.05 indicating significant differences. RESULTS: A decrease in radiation dose (22%) was achieved at Sn100 kV for the average-sized phantom. For the large phantom, Sn100 and Sn140 kV resulted in a decrease in radiation doses of 19% and 3%, respectively. Irrespective of CAC density, Sn100 and 140 kVp did not result in significantly different CNR. Only at Sn100 kV were there no significant differences in Agatston scores for all CAC densities, heart rates, and phantom sizes. CONCLUSION: PCCT at tube voltage of 100 kV with added tin filtration and reconstructed at 70 keV enables a ≥ 19% dose reduction compared to 120 kV, independent of phantom size, CAC density, and heart rate. KEY POINTS: • Photon-counting CT allows for reduced radiation dose acquisitions (up to 19%) for coronary calcium assessment by reducing tube voltage while reconstructing at a normal monoE level of 70 keV. • Tube voltage reduction is possible for medium and large patient sizes, without affecting the Agatston score outcome.

Long-term effects of the interruption of the Dutch breast cancer screening program due to COVID-19: A modelling study.

Due to COVID-19, the Dutch breast cancer screening program was interrupted for three months with uncertain long-term effects. The aim of this study was to estimate the long-term impact of this interruption on delay in detection, tumour size of screen-detected breast cancers, and interval cancer rate. After validation, the micro-simulation model SiMRiSc was used to calculate the effects of interruption of the breast cancer screening program for three months and for hypothetical interruptions of six and twelve months. A scenario without interruption was used as reference. Outcomes considered were tumour size of screen-detected breast cancers and interval cancer rate. Women of 55-59 and 60-64 years old at time of interruption were considered. Uncertainties were estimated using a sensitivity analysis. The three-month interruption had no clinically relevant long-term effect on the tumour size of screen-detected breast cancers. A 19% increase in interval cancer rate was found between last screening before and first screening after interruption compared to no interruption. Hypothetical interruptions of six and twelve months resulted in larger increases in interval cancer rate of 38% and 78% between last screening before and first screening after interruption, respectively, and an increase in middle-sized tumours in first screening after interruption of 26% and 47%, respectively. In conclusion, the interruption of the Dutch screening program is not expected to result in a long-term delay in detection or clinically relevant change in tumour size of screen-detected cancers, but only affects the interval cancer rate between last screening before and first screening after interruption.

Performance of visual, manual, and automatic coronary calcium scoring of cardiac 13N-ammonia PET/low dose CT.

BACKGROUND: Coronary artery calcium is a well-known predictor of major adverse cardiac events and is usually scored manually from dedicated, ECG-triggered calcium scoring CT (CSCT) scans. In clinical practice, a myocardial perfusion PET scan is accompanied by a non-ECG triggered low dose CT (LDCT) scan. In this study, we investigated the accuracy of patients' cardiovascular risk categorisation based on manual, visual, and automatic AI calcium scoring using the LDCT scan. METHODS: We retrospectively enrolled 213 patients. Each patient received a 13N-ammonia PET scan, an LDCT scan, and a CSCT scan as the gold standard. All LDCT and CSCT scans were scored manually, visually, and automatically. For the manual scoring, we used vendor recommended software (Syngo.via, Siemens). For visual scoring a 6-points risk scale was used (0; 1-10; 11-100; 101-400; 401-100; > 1 000 Agatston score). The automatic scoring was performed with deep learning software (Syngo.via, Siemens). All manual and automatic Agatston scores were converted to the 6-point risk scale. Manual CSCT scoring was used as a reference. RESULTS: The agreement of manual and automatic LDCT scoring with the reference was low [weighted kappa 0.59 (95% CI 0.53-0.65); 0.50 (95% CI 0.44-0.56), respectively], but the agreement of visual LDCT scoring was strong [0.82 (95% CI 0.77-0.86)]. CONCLUSIONS: Compared with the gold standard manual CSCT scoring, visual LDCT scoring outperformed manual LDCT and automatic LDCT scoring.

Coronary calcium scores on dual-source photon-counting computed tomography: an adapted Agatston methodology aimed at radiation dose reduction.

OBJECTIVES: The aim of this study was to determine mono-energetic (monoE) level-specific photon-counting CT (PCCT) Agatston thresholds, to yield monoE level independent Agatston scores validated with a dynamic cardiac phantom. Also, we examined the potential of dose reduction for PCCT coronary artery calcium (CAC) studies, when reconstructed at low monoE levels. METHODS: Theoretical CAC monoE thresholds were calculated with data from the National Institute of Standards and Technology (NIST) database. Artificial CAC with three densities were moved in an anthropomorphic thorax phantom at 0 and 60-75 bpm, and scanned at full and 50% dose on a first-generation dual-source PCCT. For all densities, Agatston scores and maximum CT numbers were determined. Agatston scores were compared with the reference at full dose and 70 keV monoE level; deviations (95% confidence interval) < 10% were deemed to be clinically not-relevant. RESULTS: Averaged over all monoE levels, measured CT numbers deviated from theoretical CT numbers by 6%, 13%, and - 4% for low-, medium-, and high-density CAC, respectively. At 50% reduced dose and 60-75 bpm, Agatston score deviations were non-relevant for 60 to 100 keV and 60 to 120 keV for medium- and high-density CAC, respectively. CONCLUSION: MonoE level-specific Agatston score thresholds resulted in similar scores as in standard reconstructions at 70 keV. PCCT allows for a potential dose reduction of 50% for CAC scoring using low monoE reconstructions for medium- and high-density CAC. KEY POINTS: • Mono-energy level-specific Agatston thresholds allow for reproducible coronary artery calcium quantification on mono-energetic images. • Increased calcium contrast-to-noise ratio at reduced mono-energy levels allows for coronary artery calcium quantification at 50% reduced radiation dose for medium- and high-density calcifications.

Evaluating a calcium-aware kernel for CT CAC scoring with varying surrounding materials and heart rates: a dynamic phantom study.

OBJECTIVES: The purpose of this study was twofold. First, the influence of a novel calcium-aware (Ca-aware) computed tomography (CT) reconstruction technique on coronary artery calcium (CAC) scores surrounded by a variety of tissues was assessed. Second, the performance of the Ca-aware reconstruction technique on moving CAC was evaluated with a dynamic phantom. METHODS: An artificial coronary artery, containing two CAC of equal size and different densities (196 ± 3, 380 ± 2 mg hydroxyapatite cm-3), was moved in the center compartment of an anthropomorphic thorax phantom at different heart rates. The center compartment was filled with mixtures, which resembled fat, water, and soft tissue equivalent CT numbers. Raw data was acquired with a routine clinical CAC protocol, at 120 peak kilovolt (kVp). Subsequently, reduced tube voltage (100 kVp) and tin-filtration (150Sn kVp) acquisitions were performed. Raw data was reconstructed with a standard and a novel Ca-aware reconstruction technique. Agatston scores of all reconstructions were compared with the reference (120 kVp) and standard reconstruction technique, with relevant deviations defined as > 10%. RESULTS: For all heart rates, Agatston scores for CAC submerged in fat were comparable to the reference, for the reduced-kVp acquisition with Ca-aware reconstruction kernel. For water and soft tissue, medium-density Agatston scores were again comparable to the reference for all heart rates. Low-density Agatston scores showed relevant deviations, up to 15% and 23% for water and soft tissue, respectively. CONCLUSION: CT CAC scoring with varying surrounding materials and heart rates is feasible at patient-specific tube voltages with the novel Ca-aware reconstruction technique. KEY POINTS: • A dedicated calcium-aware reconstruction kernel results in similar Agatston scores for CAC surrounded by fatty materials regardless of CAC density and heart rate. • Application of a dedicated calcium-aware reconstruction kernel allows for radiation dose reduction. • Mass scores determined with CT underestimated physical mass.

Motion-corrected coronary calcium scores by a convolutional neural network: a robotic simulating study.

OBJECTIVE: To classify motion-induced blurred images of calcified coronary plaques so as to correct coronary calcium scores on nontriggered chest CT, using a deep convolutional neural network (CNN) trained by images of motion artifacts. METHODS: Three artificial coronary arteries containing nine calcified plaques of different densities (high, medium, and low) and sizes (large, medium, and small) were attached to a moving robotic arm. The artificial arteries moving at 0-90 mm/s were scanned to generate nine categories (each from one calcified plaque) of images with motion artifacts. An inception v3 CNN was fine-tuned and validated. Agatston scores of the predicted classification by CNN were considered as corrected scores. Variation of Agatston scores on moving plaque and by CNN correction was calculated using the scores at rest as reference. RESULTS: The overall accuracy of CNN classification was 79.2 ± 6.1% for nine categories. The accuracy was 88.3 ± 4.9%, 75.9 ± 6.4%, and 73.5 ± 5.0% for the high-, medium-, and low-density plaques, respectively. Compared with the Agatston score at rest, the overall median score variation was 37.8% (1st and 3rd quartile, 10.5% and 68.8%) in moving plaques. CNN correction largely decreased the variation to 3.7% (1.9%, 9.1%) (p < 0.001, Mann-Whitney U test) and improved the sensitivity (percentage of non-zero scores among all the scores) from 65 to 85% for detection of coronary calcifications. CONCLUSIONS: In this experimental study, CNN showed the ability to classify motion-induced blurred images and correct calcium scores derived from nontriggered chest CT. CNN correction largely reduces the overall Agatston score variation and increases the sensitivity to detect calcifications. KEY POINTS: • A deep CNN architecture trained by CT images of motion artifacts showed the ability to correct coronary calcium scores from blurred images. • A correction algorithm based on deep CNN can be used for a tenfold reduction in Agatston score variations from 38 to 3.7% of moving coronary calcified plaques and to improve the sensitivity from 65 to 85% for the detection of calcifications. • This experimental study provides a method to improve its accuracy for coronary calcium scores that is a fundamental step towards a real clinical scenario.

The cost-effectiveness of digital breast tomosynthesis in a population breast cancer screening program.

OBJECTIVES: To evaluate at which sensitivity digital breast tomosynthesis (DBT) would become cost-effective compared to digital mammography (DM) in a population breast cancer screening program, given a constant estimate of specificity. METHODS: In a microsimulation model, the cost-effectiveness of biennial screening for women aged 50-75 was simulated for three scenarios: DBT for women with dense breasts and DM for women with fatty breasts (scenario 1), DBT for the whole population (scenario 2) or maintaining DM screening (reference). For DM, sensitivity was varied depending on breast density from 65 to 87%, and for DBT from 65 to 100%. The specificity was set at 96.5% for both DM and DBT. Direct medical costs were considered, including screening, biopsy and treatment costs. Scenarios were considered to be cost-effective if the incremental cost-effectiveness ratio (ICER) was below €20,000 per life year gain (LYG). RESULTS: For both scenarios, the ICER was more favourable at increasing DBT sensitivity. Compared with DM screening, 0.8-10.2% more LYGs were found when DBT sensitivity was at least 75% for scenario 1, and 4.7-18.7% when DBT sensitivity was at least 80% for scenario 2. At €96 per DBT, scenario 1 was cost-effective at a DBT sensitivity of at least 90%, and at least 95% for scenario 2. At €80 per DBT, these values decreased to 80% and 90%, respectively. CONCLUSION: DBT is more likely to be a cost-effective alternative to mammography in women with dense breasts. Whether DBT could be cost-effective in a general population highly depends on DBT costs. KEY POINTS: • DBT could be a cost-effective screening modality for women with dense breasts when its sensitivity is at least 90% at a maximum cost per screen of €96. • DBT has the potential to be cost-effective for screening all women when sensitivity is at least 90% at a maximum cost per screen of €80. • Whether DBT could be used as an alternative to mammography for screening all women is highly dependent on the cost of DBT per screen.

Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts - a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. METHODS: Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. RESULTS: Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63). CONCLUSION: In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

Feasibility of spectral shaping for detection and quantification of coronary calcifications in ultra-low dose CT.

OBJECTIVES: To evaluate detectability and quantification of coronary calcifications for CT with a tin filter for spectral shaping. METHODS: Phantom inserts with 100 small and 9 large calcifications, and a moving artificial artery with 3 calcifications (speed 0-30 mm/s) were placed in a thorax phantom simulating different patient sizes. The phantom was scanned in high-pitch spiral mode at 100 kVp with tin filter (Sn100 kVp), and at a reference of 120 kVp, with electrocardiographic (ECG) gating. Detectability and quantification of calcifications were analyzed for standard (130 HU) and adapted thresholds. RESULTS: Sn100 kVp yielded lower detectability of calcifications (9 % versus 12 %, p = 0.027) and lower Agatston scores (p < 0.008), irrespective of calcification, patient size and speed. Volume scores of the moving calcifications for Sn100 kVp at speed 10-30 mm/s were lower (p < 0.001), while mass scores were similar (p = 0.131). For Sn100 kVp with adapted threshold of 117 HU, detectability (p = 1.000) and Agatston score (p > 0.206) were similar to 120 kVp. Spectral shaping resulted in median dose reduction of 62.3 % (range 59.0-73.4 %). CONCLUSIONS: Coronary calcium scanning with spectral shaping yields lower detectability of calcifications and lower Agatston scores compared to 120 kVp scanning, for which a HU threshold correction should be developed. KEY POINTS: • Sn100kVp yields lower detectability and lower Agatston scores compared to 120kVp • Adapted HU threshold for Sn100kVp provides Agatston scores comparable to 120kVp • Sn100 kVp considerably reduces dose in calcium scoring versus 120 kVp.

Small irregular pulmonary nodules in low-dose CT: observer detection sensitivity and volumetry accuracy.

OBJECTIVE: The purpose of this study is to evaluate observer detection and volume measurement of small irregular solid artificial pulmonary nodules on 64-MDCT in an anthropomorphic thoracic phantom. MATERIALS AND METHODS: Forty in-house-made solid pulmonary nodules (lobulated and spiculated; actual volume, 5.1-88.4 mm3; actual CT densities, -51 to 157 HU) were randomly placed inside an anthropomorphic thoracic phantom with pulmonary vasculature. The phantom was examined on two 64-MDCT scanners, using a scan protocol as applied in lung cancer screening. Two independent blinded observers screened for pulmonary nodules. Nodule volume was evaluated semiautomatically using dedicated software and was compared with the actual volume using an independent-samples t test. The interscanner and interobserver agreement of volumetry was assessed using Bland-Altman analysis. RESULTS: Observer detection sensitivity increased along with increasing size of irregular nodules. Sensitivity was 100% when the actual volume was at least 69 mm3, regardless of specific observer, scanner, nodule shape, and density. Overall, nodule volume was underestimated by (mean±SD) 18.9±11.8 mm3 (39%±21%; p<0.001). The relative interscanner difference of volumetry was 3.3% (95% CI, -33.9% to 40.4%). The relative interobserver difference was 0.6% (-33.3% to 34.5%). CONCLUSION: Small irregular solid pulmonary nodules with an actual volume of at least 69 mm3 are reliably detected on 64-MDCT. However, CT-derived volume of those small nodules is largely underestimated, with considerable variation.

Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study.

Computed tomography (CT) scans are indispensable in modern medicine; however, the spectacular rise in global use coupled with relatively high doses of ionizing radiation per examination have raised radiation protection concerns. Children are of particular concern because they are more sensitive to radiation-induced cancer compared with adults and have a long lifespan to express harmful effects which may offset clinical benefits of performing a scan. This paper describes the design and methodology of a nationwide study, the Dutch Pediatric CT Study, regarding risk of leukemia and brain tumors in children after radiation exposure from CT scans. It is a retrospective record-linkage cohort study with an expected number of 100,000 children who received at least one electronically archived CT scan covering the calendar period since the introduction of digital archiving until 2012. Information on all archived CT scans of these children will be obtained, including date of examination, scanned body part and radiologist's report, as well as the machine settings required for organ dose estimation. We will obtain cancer incidence by record linkage with external databases. In this article, we describe several approaches to the collection of data on archived CT scans, the estimation of radiation doses and the assessment of confounding. The proposed approaches provide useful strategies for data collection and confounder assessment for general retrospective record-linkage studies, particular those using hospital databases on radiological procedures for the assessment of exposure to ionizing or non-ionizing radiation.

Willingness of healthcare providers to perform population-based cancer screening: a cross-sectional study in primary healthcare institutions in Tianjin, China.

OBJECTIVE: To evaluate the willingness of healthcare providers to perform population-based screening in primary healthcare institutions in China. METHODS: Healthcare providers of 262 primary healthcare institutions in Tianjin were invited to fill out a questionnaire consisting of demographic characteristics, workload, and knowledge of, attitude towards and willingness to perform breast, cervical and colorectal cancer screening. Willingness to screen was the primary outcome. Multilevel logistic regression models were conducted to analyse the determinants of healthcare providers' willingness to screen. ORs and 95% CIs were estimated. RESULTS: A total of 554 healthcare providers from 244 institutions answered the questionnaire. 67.2%, 72.1% and 74.3% were willing to perform breast, cervical and colorectal cancer screening, respectively. A negative attitude towards screening was associated with a low willingness for cervical (OR=0.27; 95% CI 0.08, 0.94) and colorectal (OR=0.08; 95% CI 0.02, 0.30) cancer screening, while this was not statistically significant for breast cancer screening (OR=0.30; 95% CI 0.08, 1.12). For breast, cervical and colorectal cancer screening, 70.1%, 63.8% and 59.0% of healthcare providers reported a shortage of staff dedicated to screening. A perceived reasonable manpower allocation was a determinant of increased willingness to perform breast (OR=2.86; 95% CI 1.03, 7.88) and colorectal (OR=2.70; 95% CI 1.22, 5.99) cancer screening. However, this was not significant for cervical cancer screening (OR=1.76; 95% CI 0.74, 4.18). CONCLUSIONS: In China, healthcare providers with a positive attitude towards screening have a stronger willingness to contribute to cancer screening, and therefore healthcare providers' attitude, recognition of the importance of screening and acceptable workload should be optimised to improve the uptake of cancer screening.

Reliability, costs, and radiation dose of dual-energy X-ray absorptiometry in diagnosis of radiologic sarcopenia in surgically menopausal women.

OBJECTIVE: The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis of sarcopenia. METHODS: Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute. RESULTS: The 34 participants had a median age of 58 years (IQR 53-65) and a median body mass index of 24.6 (IQR 21.7-29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994-0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996-0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993-0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5-3.0 mSv, for DXA this was 2-4 µSv. CONCLUSIONS: DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass. TRIAL REGISTRATION: Netherlands Trial Register; NL8068. CRITICAL RELEVANCE STATEMENT: DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low. KEY POINTS: • Screening for sarcopenia should be optimized as the population ages. • DXA outperformed CT and MRI in the measured metrics. • DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation.

Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals.

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

Sensitivity and accuracy of volumetry of pulmonary nodules on low-dose 16- and 64-row multi-detector CT: an anthropomorphic phantom study.

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

Pricing and cost-saving potential for deep-learning computer-aided lung nodule detection software in CT lung cancer screening.

OBJECTIVE: An increasing number of commercial deep learning computer-aided detection (DL-CAD) systems are available but their cost-saving potential is largely unknown. This study aimed to gain insight into appropriate pricing for DL-CAD in different reading modes to be cost-saving and to determine the potentially most cost-effective reading mode for lung cancer screening. METHODS: In three representative settings, DL-CAD was evaluated as a concurrent, pre-screening, and second reader. Scoping review was performed to estimate radiologist reading time with and without DL-CAD. Hourly cost of radiologist time was collected for the USA (€196), UK (€127), and Poland (€45), and monetary equivalence of saved time was calculated. The minimum number of screening CTs to reach break-even was calculated for one-time investment of €51,616 for DL-CAD. RESULTS: Mean reading time was 162 (95% CI: 111-212) seconds per case without DL-CAD, which decreased by 77 (95% CI: 47-107) and 104 (95% CI: 71-136) seconds for DL-CAD as concurrent and pre-screening reader, respectively, and increased by 33-41 s for DL-CAD as second reader. This translates into €1.0-4.3 per-case cost for concurrent reading and €0.8-5.7 for pre-screening reading in the USA, UK, and Poland. To achieve break-even with a one-time investment, the minimum number of CT scans was 12,300-53,600 for concurrent reader, and 9400-65,000 for pre-screening reader in the three countries. CONCLUSIONS: Given current pricing, DL-CAD must be priced substantially below €6 in a pay-per-case setting or used in a high-workload environment to reach break-even in lung cancer screening. DL-CAD as pre-screening reader shows the largest potential to be cost-saving. CRITICAL RELEVANCE STATEMENT: Deep-learning computer-aided lung nodule detection (DL-CAD) software must be priced substantially below 6 euro in a pay-per-case setting or must be used in high-workload environments with one-time investment in order to achieve break-even. DL-CAD as a pre-screening reader has the greatest cost savings potential. KEY POINTS: • DL-CAD must be substantially below €6 in a pay-per-case setting to reach break-even. • DL-CAD must be used in a high-workload screening environment to achieve break-even. • DL-CAD as a pre-screening reader shows the largest potential to be cost-saving.

The natural history of ductal carcinoma in situ (DCIS) in simulation models: A systematic review.

OBJECTIVE: Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women. METHODS: A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression. RESULTS: Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk. CONCLUSION: To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.

Effectiveness of Colorectal Cancer (CRC) Screening on All-Cause and CRC-Specific Mortality Reduction: A Systematic Review and Meta-Analysis.

(1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62-1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.