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Purpose Low back pain (LBP) is one of the most prevalent health condition worldwide and responsible for the most years lived with disability, yet the etiology is often unknown. Magnetic resonance imaging (MRI) is frequently used for treatment decision even though it is often inconclusive. There are many different image features that could relate to low back pain. Conversely, multiple etiologies do relate to spinal degeneration but do not actually cause the perceived pain. This narrative review provides an overview of all possible relevant features visible on MRI images and determines their relation to LBP. Methods We conducted a separate literature search per image feature. All included studies were scored using the GRADE guidelines. Based on the reported results per feature an evidence agreement (EA) score was provided, enabling us to compare the collected evidence of separate image features. The various relations between MRI features and their associated pain mechanisms were evaluated to provide a list of features that are related to LBP. Results All searches combined generated a total of 4472 hits of which 31 articles were included. Features were divided into five different categories:’discogenic’, ‘neuropathic’,’osseous’, ‘facetogenic’, and’paraspinal’, and discussed separately. Conclusion Our research suggests that type I Modic changes, disc degeneration, endplate defects, disc herniation, spinal canal stenosis, nerve compression, and muscle fat infiltration have the highest probability to be related to LBP. These can be used to improve clinical decision-making for patients with LBP based on MRI.

Contains fulltext : 251973.pdf (Publisher’s version ) (Closed access) Amidst the ongoing pandemic, the assessment of computed tomography (CT) images for COVID-19 presence can exceed the workload capacity of radiologists. Several studies addressed this issue by automating COVID-19 classification and grading from CT images with convolutional neural networks (CNNs). Many of these studies reported initial results of algorithms that were assembled from commonly used components. However, the choice of the components of these algorithms was often pragmatic rather than systematic and systems were not compared to each other across papers in a fair manner. We systematically investigated the effectiveness of using 3-D CNNs instead of 2-D CNNs for seven commonly used architectures, including DenseNet, Inception, and ResNet variants. For the architecture that performed best, we furthermore investigated the effect of initializing the network with pretrained weights, providing automatically computed lesion maps as additional network input, and predicting a continuous instead of a categorical output. A 3-D DenseNet-201 with these components achieved an area under the receiver operating characteristic curve of 0.930 on our test set of 105 CT scans and an AUC of 0.919 on a publicly available set of 742 CT scans, a substantial improvement in comparison with a previously published 2-D CNN. This article provides insights into the performance benefits of various components for COVID-19 classification and grading systems. We have created a challenge on grand-challenge.org to allow for a fair comparison between the results of this and future research.

Contains fulltext : 235298.pdf (Publisher’s version ) (Open Access) Importance: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. Objective: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. Design, Setting, and Participants: In this multicenter cohort study of 15915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Exposures: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Main Outcomes and Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). Conclusions and Relevance: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.

Purpose Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD). Methods In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae. Results 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812–3584) vs 1182 (235–2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: − 0.02 [− 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: − 2.06 [− 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo. Conclusion Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044

Contains fulltext : 251974.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 252007.pdf (Publisher’s version ) (Open Access) Purpose: Ensembles of convolutional neural networks (CNNs) often outperform a single CNN in medical image segmentation tasks, but inference is computationally more expensive and makes ensembles unattractive for some applications. We compared the performance of differently constructed ensembles with the performance of CNNs derived from these ensembles using knowledge distillation, a technique for reducing the footprint of large models such as ensembles. Approach: We investigated two different types of ensembles, namely, diverse ensembles of networks with three different architectures and two different loss-functions, and uniform ensembles of networks with the same architecture but initialized with different random seeds. For each ensemble, additionally, a single student network was trained to mimic the class probabilities predicted by the teacher model, the ensemble. We evaluated the performance of each network, the ensembles, and the corresponding distilled networks across three different publicly available datasets. These included chest computed tomography scans with four annotated organs of interest, brain magnetic resonance imaging (MRI) with six annotated brain structures, and cardiac cine-MRI with three annotated heart structures. Results: Both uniform and diverse ensembles obtained better results than any of the individual networks in the ensemble. Furthermore, applying knowledge distillation resulted in a single network that was smaller and faster without compromising performance compared with the ensemble it learned from. The distilled networks significantly outperformed the same network trained with reference segmentation instead of knowledge distillation. Conclusion: Knowledge distillation can compress segmentation ensembles of uniform or diverse composition into a single CNN while maintaining the performance of the ensemble.

BackgroundA baseline computed tomography (CT) scan for lung cancer (LC) screening may reveal information indicating that certain LC screening participants can be screened less, and instead require dedicated early cardiac and respiratory clinical input. We aimed to develop and validate competing death (CD) risk models using CT information to identify participants with a low LC risk and a high CD risk.MethodsParticipant demographics and quantitative CT measures of LC, cardiovascular disease and chronic obstructive pulmonary disease were considered for deriving a logistic regression model for predicting 5-year CD risk using a sample from the National Lung Screening Trial (n=15 000). Multicentric Italian Lung Detection data were used to perform external validation (n=2287).ResultsOur final CD model outperformed an external pre-scan model (CD Risk Assessment Tool) in both the derivation (area under the curve (AUC) 0.744 (95% CI 0.727–0.761) and 0.677 (95% CI 0.658–0.695), respectively) and validation cohorts (AUC 0.744 (95% CI 0.652–0.835) and 0.725 (95% CI 0.633–0.816), respectively). By also taking LC incidence risk into consideration, we suggested a risk threshold where a subgroup (6258/23 096 (27%)) was identified with a number needed to screen to detect one LC of 216 (versus 23 in the remainder of the cohort) and ratio of 5.41 CDs per LC case (versus 0.88). The respective values in the validation cohort subgroup (774/2287 (34%)) were 129 (versus 29) and 1.67 (versus 0.43).ConclusionsEvaluating both LC and CD risks post-scan may improve the efficiency of LC screening and facilitate the initiation of multidisciplinary trajectories among certain participants.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration ap- proaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi- task medical image registration data set for comprehen- sive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https:// learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, ac- curacy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image regis- tration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state- of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17–1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27–1.80) and EV-TEX; OR 1.21 (95% CI 1.02–1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.

MR images of fetuses allow clinicians to detect brain abnormalities in an early stage of development. The cornerstone of volumetric and morphologic analysis in fetal MRI is segmentation of the fetal brain into different tissue classes. Manual segmentation is cumbersome and time consuming, hence automatic segmentation could substantially simplify the procedure. However, automatic brain tissue segmentation in these scans is challenging owing to artifacts including intensity inhomogeneity, caused in particular by spontaneous fetal movements during the scan. Unlike methods that estimate the bias field to remove intensity inhomogeneity as a preprocessing step to segmentation, we propose to perform segmentation using a convolutional neural network that exploits images with synthetically introduced intensity inhomogeneity as data augmentation. The method first uses a CNN to extract the intracranial volume. Thereafter, another CNN with the same architecture is employed to segment the extracted volume into seven brain tissue classes: cerebellum, basal ganglia and thalami, ventricular cerebrospinal fluid, white matter, brain stem, cortical gray matter and extracerebral cerebrospinal fluid. To make the method applicable to slices showing intensity inhomogeneity artifacts, the training data was augmented by applying a combination of linear gradients with random offsets and orientations to image slices without artifacts., Comment: Published in Magnetic Resonance Imaging, 2019

Purpose The purpose of this study was to elucidate the impact of being unmarried on coronary computed tomography (CT) imaging biomarkers and mortality in a lung cancer screening population. Materials and methods In this retrospective case-control study, 5707 subjects (3777 married; mean age: 61.9±5.1 y and 1930 unmarried; mean age: 61.9±5.3 y) underwent low-dose CT as part of the National Lung Screening Trial (NLST). The median follow-up time was 6.5 (Q1-Q3: 5.6 to 6.9) years. Being unmarried was defined as never married, widowed, separated, or divorced. Being married was defined as married or living as married. Our primary endpoint was cardiovascular disease (CVD)-related death; our secondary endpoint was all-cause mortality. Coronary CT imaging biomarkers (calcium score, density, and volume) on low-dose chest CT scan were calculated using dedicated automatic software. Weighted Cox proportional-hazards regression was performed to examine the association between marital status and death. Kaplan-Meier curves were generated to visualize subject survival. Results Being unmarried was significantly associated with an increased risk for CVD-related death (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.31-1.91) and all-cause mortality (HR: 1.39; 95% CI: 1.26-1.53), which remained significant even after adjusting for traditional cardiovascular risk factors (HR CVD death: 1.75; 1.44-2.12 and HR all-cause mortality: 1.58; 95% CI: 1.43-1.74) and coronary calcium score (HR CVD death: 1.58; 95% CI: 1.31-1.91 and HR all-cause mortality: 1.40; 95% CI: 1.27-1.54). Conclusions Being unmarried is associated with an increased CVD-related death and all-cause mortality mainly due to cardiovascular etiology. On the basis of this, marital status might be taken into consideration when assessing individuals' health status.

Objectives The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening. Background CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry. Methods We performed a nested case–control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality. Results CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease. Conclusions CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

Cardiovascular disease (CVD) is the global leading cause of death. A strong risk factor for CVD events is the amount of coronary artery calcium (CAC). To meet demands of the increasing interest in quantification of CAC, i.e. coronary calcium scoring, especially as an unrequested finding for screening and research, automatic methods have been proposed. Current automatic calcium scoring methods are relatively computationally expensive and only provide scores for one type of CT. To address this, we propose a computationally efficient method that employs two ConvNets: the first performs registration to align the fields of view of input CTs and the second performs direct regression of the calcium score, thereby circumventing time-consuming intermediate CAC segmentation. Optional decision feedback provides insight in the regions that contributed to the calcium score. Experiments were performed using 903 cardiac CT and 1,687 chest CT scans. The method predicted calcium scores in less than 0.3 s. Intra-class correlation coefficient between predicted and manual calcium scores was 0.98 for both cardiac and chest CT. The method showed almost perfect agreement between automatic and manual CVD risk categorization in both datasets, with a linearly weighted Cohen's kappa of 0.95 in cardiac CT and 0.93 in chest CT. Performance is similar to that of state-of-the-art methods, but the proposed method is hundreds of times faster. By providing visual feedback, insight is given in the decision process, making it readily implementable in clinical and research settings., Comment: IEEE Transactions on Medical Imaging (In press)

Contains fulltext : 235733.pdf (Publisher’s version ) (Closed access) Purpose: To examine the prognostic value of location-specific arterial calcification quantities at lung screening low-dose CT for the prediction of cardiovascular disease (CVD) mortality. Materials and Methods: This retrospective study included 5564 participants who underwent low-dose CT from the National Lung Screening Trial between August 2002 and April 2004, who were followed until December 2009. A deep learning network was trained to quantify six types of vascular calcification: thoracic aorta calcification (TAC); aortic and mitral valve calcification; and coronary artery calcification (CAC) of the left main, the left anterior descending, and the right coronary artery. TAC and CAC were determined in six evenly distributed slabs spatially aligned among chest CT images. CVD mortality prediction was performed with multivariable logistic regression using least absolute shrinkage and selection operator. The methods were compared with semiautomatic baseline prediction using self-reported participant characteristics, such as age, history of smoking, and history of illness. Statistical significance between the prediction models was tested using the nonparametric DeLong test. Results: The prediction model was trained with data from 4451 participants (median age, 61 years; 37.9% women) and then tested on data from 1113 participants (median age, 61 years; 37.9% women). The prediction model using calcium scores achieved a C statistic of 0.74 (95% CI: 0.69, 0.79), and it outperformed the baseline model using only participant characteristics (C statistic, 0.69; P = .049). Best results were obtained when combining all variables (C statistic, 0.76; P < .001). Conclusion: Five-year CVD mortality prediction using automatically extracted image-based features is feasible at lung screening low-dose CT.(c) RSNA, 2021.

Deep-learning-based registration methods emerged as a fast alternative to conventional registration methods. However, these methods often still cannot achieve the same performance as conventional registration methods because they are either limited to small deformation or they fail to handle a superposition of large and small deformations without producing implausible deformation fields with foldings inside. In this paper, we identify important strategies of conventional registration methods for lung registration and successfully developed the deep-learning counterpart. We employ a Gaussian-pyramid-based multilevel framework that can solve the image registration optimization in a coarse-to-fine fashion. Furthermore, we prevent foldings of the deformation field and restrict the determinant of the Jacobian to physiologically meaningful values by combining a volume change penalty with a curvature regularizer in the loss function. Keypoint correspondences are integrated to focus on the alignment of smaller structures. We perform an extensive evaluation to assess the accuracy, the robustness, the plausibility of the estimated deformation fields, and the transferability of our registration approach. We show that it achieves state-of-the-art results on the COPDGene dataset compared to conventional registration method with much shorter execution time. In our experiments on the DIRLab exhale to inhale lung registration, we demonstrate substantial improvements (TRE below $1.2$ mm) over other deep learning methods. Our algorithm is publicly available at https://grand-challenge.org/algorithms/deep-learning-based-ct-lung-registration/.

Background The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed. Purpose To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems. Materials and Methods The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted κ values, and classification accuracy. Results A total of 105 patients (mean age, 62 years ± 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years ± 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted κ values of 0.60 ± 0.01 for CO-RADS scores and 0.54 ± 0.01 for CT severity scores. Conclusion With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. © RSNA, 2020 Supplemental material is available for this article.

Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision-support systems for diagnosis, surgery planning, and population-based analysis on spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms towards labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel-level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the the results of this evaluation and further investigate the performance-variation at vertebra-level, scan-level, and at different fields-of-view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The content and code concerning VerSe can be accessed at: https://github.com/anjany/verse., Comment: Challenge report for the VerSe 2019 and 2020. Published in Medical Image Analysis (DOI: https://doi.org/10.1016/j.media.2021.102166)

ObjectivesCombined assessment of cardiovascular disease (CVD), COPD and lung cancer may improve the effectiveness of lung cancer screening in smokers. The aims were to derive and assess risk models for predicting lung cancer incidence, CVD mortality and COPD mortality by combining quantitative computed tomography (CT) measures from each disease, and to quantify the added predictive benefit of self-reported patient characteristics given the availability of a CT scan.MethodsA survey model (patient characteristics only), CT model (CT information only) and final model (all variables) were derived for each outcome using parsimonious Cox regression on a sample from the National Lung Screening Trial (n=15 000). Validation was performed using Multicentric Italian Lung Detection data (n=2287). Time-dependent measures of model discrimination and calibration are reported.ResultsAge, mean lung density, emphysema score, bronchial wall thickness and aorta calcium volume are variables that contributed to all final models. Nodule features were crucial for lung cancer incidence predictions but did not contribute to CVD and COPD mortality prediction. In the derivation cohort, the lung cancer incidence CT model had a 5-year area under the receiver operating characteristic curve of 82.5% (95% CI 80.9–84.0%), significantly inferior to that of the final model (84.0%, 82.6–85.5%). However, the addition of patient characteristics did not improve the lung cancer incidence model performance in the validation cohort (CT model 80.1%, 74.2–86.0%; final model 79.9%, 73.9–85.8%). Similarly, the final CVD mortality model outperformed the other two models in the derivation cohort (survey model 74.9%, 72.7–77.1%; CT model 76.3%, 74.1–78.5%; final model 79.1%, 77.0–81.2%), but not the validation cohort (survey model 74.8%, 62.2–87.5%; CT model 72.1%, 61.1–83.2%; final model 72.2%, 60.4–84.0%). Combining patient characteristics and CT measures provided the largest increase in accuracy for the COPD mortality final model (92.3%, 90.1–94.5%) compared to either other model individually (survey model 87.5%, 84.3–90.6%; CT model 87.9%, 84.8–91.0%), but no external validation was performed due to a very low event frequency.ConclusionsCT measures of CVD and COPD provides small but reproducible improvements to nodule-based lung cancer risk prediction accuracy from 3 years onwards. Self-reported patient characteristics may not be of added predictive value when CT information is available.

BACKGROUND: Although several deep learning (DL) calcium scoring methods have achieved excellent performance for specific CT protocols, their performance in a range of CT examination types is unknown. PURPOSE: To evaluate the performance of a DL method for automatic calcium scoring across a wide range of CT examination types and to investigate whether the method can adapt to different types of CT examinations when representative images are added to the existing training data set. MATERIALS AND METHODS: The study included 7240 participants who underwent various types of nonenhanced CT examinations that included the heart: coronary artery calcium (CAC) scoring CT, diagnostic CT of the chest, PET attenuation correction CT, radiation therapy treatment planning CT, CAC screening CT, and low-dose CT of the chest. CAC and thoracic aorta calcification (TAC) were quantified using a convolutional neural network trained with (a) 1181 low-dose chest CT examinations (baseline), (b) a small set of examinations of the respective type supplemented to the baseline (data specific), and (c) a combination of examinations of all available types (combined). Supplemental training sets contained 199–568 CT images depending on the calcium burden of each population. The DL algorithm performance was evaluated with intraclass correlation coefficients (ICCs) between DL and manual (Agatston) CAC and (volume) TAC scoring and with linearly weighted κ values for cardiovascular risk categories (Agatston score; cardiovascular disease risk categories: 0, 1–10, 11–100, 101–400, >400). RESULTS: At baseline, the DL algorithm yielded ICCs of 0.79–0.97 for CAC and 0.66–0.98 for TAC across the range of different types of CT examinations. ICCs improved to 0.84–0.99 (CAC) and 0.92–0.99 (TAC) for CT protocol–specific training and to 0.85–0.99 (CAC) and 0.96–0.99 (TAC) for combined training. For assignment of cardiovascular disease risk category, the κ value for all test CT scans was 0.90 (95% confidence interval [CI]: 0.89, 0.91) for the baseline training. It increased to 0.92 (95% CI: 0.91, 0.93) for both data-specific and combined training. CONCLUSION: A deep learning calcium scoring algorithm for quantification of coronary and thoracic calcium was robust, despite substantial differences in CT protocol and variations in subject population. Augmenting the algorithm training with CT protocol–specific images further improved algorithm performance. © RSNA, 2020 See also the editorial by Vannier in this issue.

Heavy smokers undergoing screening with low-dose chest CT are affected by cardiovascular disease as much as by lung cancer. Low-dose chest CT scans acquired in screening enable quantification of atherosclerotic calcifications and thus enable identification of subjects at increased cardiovascular risk. This paper presents a method for automatic detection of coronary artery, thoracic aorta, and cardiac valve calcifications in low-dose chest CT using two consecutive convolutional neural networks. The first network identifies and labels potential calcifications according to their anatomical location and the second network identifies true calcifications among the detected candidates. This method was trained and evaluated on a set of 1744 CT scans from the National Lung Screening Trial. To determine whether any reconstruction or only images reconstructed with soft tissue filters can be used for calcification detection, we evaluated the method on soft and medium/sharp filter reconstructions separately. On soft filter reconstructions, the method achieved F 1 scores of 0.89, 0.89, 0.67, and 0.55 for coronary artery, thoracic aorta, aortic valve, and mitral valve calcifications, respectively. On sharp filter reconstructions, the F 1 scores were 0.84, 0.81, 0.64, and 0.66, respectively. Linearly weighted kappa coefficients for risk category assignment based on per subject coronary artery calcium were 0.91 and 0.90 for soft and sharp filter reconstructions, respectively. These results demonstrate that the presented method enables reliable automatic cardiovascular risk assessment in all low-dose chest CT scans acquired for lung cancer screening.

Background: Myocardial perfusion imaging (MPI) is an accurate noninvasive test for patients with suspected obstructive coronary artery disease (CAD) and coronary artery calcium (CAC) score is known to be a powerful predictor of cardiovascular events. Collection of CAC scores simultaneously with MPI is unexplored. Aim: We aimed to investigate whether automatically derived CAC scores during myocardial perfusion imaging would further improve the diagnostic accuracy of MPI to detect obstructive CAD. Methods: We analyzed 150 consecutive patients without a history of coronary revascularization with suspected obstructive CAD who were referred for 82Rb PET/CT and available coronary angiographic data. Myocardial perfusion was evaluated both semi quantitatively as well as quantitatively according to the European guidelines. CAC scores were automatically derived from the low-dose attenuation correction CT scans using previously developed software based on deep learning. Obstructive CAD was defined as stenosis >70% (or >50% in the left main coronary artery) and/or fractional flow reserve (FFR) ≤0.80. Results: In total 58% of patients had obstructive CAD of which seventy-four percent were male. Addition of CAC scores to MPI and clinical predictors significantly improved the diagnostic accuracy of MPI to detect obstructive CAD. The area under the curve (AUC) increased from 0.87 to 0.91 (p: 0.025). Sensitivity and specificity analysis showed an incremental decrease in false negative tests with our MPI + CAC approach (n = 14 to n = 4), as a consequence an increase in false positive tests was seen (n = 11 to n = 28). Conclusion: CAC scores collected simultaneously with MPI improve the detection of obstructive coronary artery disease in patients without a history of coronary revascularization. Keywords: Coronary artery calcium, Obstructive coronary artery disease, Myocardial perfusion imaging, Deep learning, Cardiovascular imaging

IntroductionThe amount of coronary artery calcium determined in CT scans is a well established predictor of cardiovascular events. However, high interscan variability of coronary calcium quantification may lead to incorrect cardiovascular risk assignment. Partial volume effect contributes to high interscan variability. Hence, we propose a method for coronary calcium quantification employing partial volume correction.MethodsTwo phantoms containing artificial coronary artery calcifications and 293 subject chest CT scans were used. The first and second phantom contained nine calcifications and the second phantom contained three artificial arteries with three calcifications of different volumes, shapes and densities. The first phantom was scanned five times with and without extension rings. The second phantom was scanned three times without and with simulated cardiac motion (10 and 30 mm/s). Chest CT scans were acquired without ECG-synchronization and reconstructed using sharp and soft kernels. Coronary calcifications were annotated employing the clinically used intensity value thresholding (130 HU). Thereafter, a threshold separating each calcification from its background was determined using an Expectation-Maximization algorithm. Finally, for each lesion the partial content of calcification in each voxel was determined depending on its intensity and the determined threshold.ResultsClinical calcium scoring resulted in overestimation of calcium volume for medium and high density calcifications in the first phantom, and overestimation of calcium volume for high density and underestimation for low density calcifications in the second phantom. With induced motion these effects were further emphasized. The proposed quantification resulted in better accuracy and substantially lower over- and underestimation of calcium volume even in presence of motion. In chest CT, the agreement between calcium scores from the two reconstructions improved when proposed method was used.ConclusionCompared with clinical calcium scoring, proposed quantification provides a better estimate of the true calcium volume in phantoms and better agreement in calcium scores between different subject scan reconstructions.

Precise segmentation and anatomical identification of the vertebrae provides the basis for automatic analysis of the spine, such as detection of vertebral compression fractures or other abnormalities. Most dedicated spine CT and MR scans as well as scans of the chest, abdomen or neck cover only part of the spine. Segmentation and identification should therefore not rely on the visibility of certain vertebrae or a certain number of vertebrae. We propose an iterative instance segmentation approach that uses a fully convolutional neural network to segment and label vertebrae one after the other, independently of the number of visible vertebrae. This instance-by-instance segmentation is enabled by combining the network with a memory component that retains information about already segmented vertebrae. The network iteratively analyzes image patches, using information from both image and memory to search for the next vertebra. To efficiently traverse the image, we include the prior knowledge that the vertebrae are always located next to each other, which is used to follow the vertebral column. This method was evaluated with five diverse datasets, including multiple modalities (CT and MR), various fields of view and coverages of different sections of the spine, and a particularly challenging set of low-dose chest CT scans. The proposed iterative segmentation method compares favorably with state-of-the-art methods and is fast, flexible and generalizable., Comment: Accepted for publication in Medical Image Analysis

Purpose: This study automatically quantified calcifications in coronary arteries (CAC) and thoracic aorta (TAC) on breast planning computed tomography (CT) scans and assessed its reproducibility compared to manual scoring. Material and Methods: Dutch (n = 1199) and Singaporean (n = 1090) breast cancer patients with radiotherapy planning CT scan were included. CAC and TAC were automatically scored using deep learning algorithm. CVD risk categories were based on Agatson CAC: 0, 1–10, 11–100, 101–400 and >400. Reliability between automatic and manual scoring was assessed in 120 randomly selected CT scans from each population, with linearly weighted kappa for CAC categories and intraclass correlation coefficient for TAC. Results: Median age was higher in Dutch patients than Singaporean patients: 57 versus 52 years. CAC and TAC increased with age and were more present in Dutch patients than Singaporean patients: 24.2% versus 17.3% and 73.0% versus 62.2%, respectively. Reliability of CAC categories and TAC was excellent in the Netherlands (0.85 (95% confidence interval (CI) = 0.77–0.93) and 0.98 (95% CI = 0.96–0.98) respectively) and Singapore (0.90 (95% CI = 0.84–0.96) and 0.99 (95% CI = 0.98–0.99) respectively). Conclusions: CAC and TAC prevalence was considerable and increased with age. Deep learning software is a reliable method to automatically measure CAC and TAC on radiotherapy breast CT scans.

We evaluated the prevalence of significant lung abnormalities on computed tomography (CT) in patients who died from a respiratory illness other than lung cancer in the National Lung Screening Trial (NLST).In this retrospective case–control study, NLST participants in the CT arm who died of respiratory illness other than lung cancer were matched for age, sex, pack-years and smoking status to a surviving control. A chest radiologist and a radiology resident blinded to the outcome independently scored baseline CT scans visually and qualitatively for the presence of emphysema, airway wall thickening and fibrotic lung disease. The prevalence of CT abnormalities was compared between cases and controls by using chi-squared tests.In total, 167 participants died from a respiratory cause other than lung cancer. The prevalence of severe emphysema, airway wall thickening and fibrotic lung disease were 28.7%versus4.8%, 26.9%versus13.2% and 18.6%versus0.5% in cases and controls, respectively. Radiological findings were significantly more prevalent in deaths compared with controls (all pCT-diagnosed severe emphysema, airway wall thickening and fibrosis were much more common in NLST participants who died from respiratory disease, and CT may provide an additional means of identifying these diseases.

Precise localization in bronchoscopy is challenging, particularly for peripheral lesions that cannot be reached by conventional bronchoscopes with a large working channel. Existing navigation methods are hampered by respiratory motion, e.g., in the lower lobes. We present an image-guided approach that considers respiratory motion and can localize instruments. We developed a rigid chest marker containing steel balls visible in X-ray images and a pattern for passive tracking with an optical camera system. An experimental setup to evaluate stereoscopic localization and to mimic chest motion was established in our interventional suite. The marker motion was recorded, and X-ray images were acquired from different angles using a standard C-arm. All coordinates were expressed with respect to the stationary tracking camera. The feasibility of motion-compensated stereoscopic localization was assessed. The orientation of the C-arm could be established with a mean error of less than $$1^{\circ }$$ . Triangulation based on two different X-ray images from different angles resulted in a mean error of 1.8 ( $$\pm $$ 0.7) mm. A similar result was obtained when the marker was moved between X-ray acquisitions, and the mean error was 1.6 ( $$\pm $$ 1.4) mm. The latencies were approximately 80 and 380 ms for tracking camera and X-ray imaging, respectively. Stereoscopic localization of a moving target was feasible. The system presents a flexible alternative for precise stereoscopic localization of a bronchoscope or instruments using a standard C-arm. We demonstrated the ability to track multiple moving markers and to compensate for respiratory motion.

The amount of coronary artery calcification (CAC) quantified in computed tomography (CT) scans enables prediction of cardiovascular disease (CVD) risk. However, interscan variability of CAC quantification is high, especially in scans made without ECG synchronization. We propose a method for automatic detection of CACs that are severely affected by cardiac motion. Subsequently, we evaluate the impact of such CACs on CAC quantification and CVD risk determination. This study includes 1000 baseline and 585 one-year follow-up low-dose chest CTs from the National Lung Screening Trial. About 415 baseline scans are used to train and evaluate a convolutional neural network that identifies observer determined CACs affected by severe motion artifacts. Therefore, 585 paired scans acquired at baseline and follow-up were used to evaluate the impact of severe motion artifacts on CAC quantification and risk categorization. Based on the CAC amount, the scans were categorized into four standard CVD risk categories. The method identified CACs affected by severe motion artifacts with 85.2% accuracy. Moreover, reproducibility of CAC scores in scan pairs is higher in scans containing mostly CACs not affected by severe cardiac motion. Hence, the proposed method enables identification of scans affected by severe cardiac motion, where CAC quantification may not be reproducible.

In patients with coronary artery stenoses of intermediate severity, the functional significance needs to be determined. Fractional flow reserve (FFR) measurement, performed during invasive coronary angiography (ICA), is most often used in clinical practice. To reduce the number of ICA procedures, we present a method for automatic identification of patients with functionally significant coronary artery stenoses, employing deep learning analysis of the left ventricle (LV) myocardium in rest coronary CT angiography (CCTA). The study includes consecutively acquired CCTA scans of 166 patients with FFR measurements. To identify patients with a functionally significant coronary artery stenosis, analysis is performed in several stages. First, the LV myocardium is segmented using a multiscale convolutional neural network (CNN). To characterize the segmented LV myocardium, it is subsequently encoded using unsupervised convolutional autoencoder (CAE). Thereafter, patients are classified according to the presence of functionally significant stenosis using an SVM classifier based on the extracted and clustered encodings. Quantitative evaluation of LV myocardium segmentation in 20 images resulted in an average Dice coefficient of 0.91 and an average mean absolute distance between the segmented and reference LV boundaries of 0.7 mm. Classification of patients was evaluated in the remaining 126 CCTA scans in 50 10-fold cross-validation experiments and resulted in an area under the receiver operating characteristic curve of 0.74 +- 0.02. At sensitivity levels 0.60, 0.70 and 0.80, the corresponding specificity was 0.77, 0.71 and 0.59, respectively. The results demonstrate that automatic analysis of the LV myocardium in a single CCTA scan acquired at rest, without assessment of the anatomy of the coronary arteries, can be used to identify patients with functionally significant coronary artery stenosis., This paper was submitted in April 2017 and accepted in November 2017 for publication in Medical Image Analysis. Please cite as: Zreik et al., Medical Image Analysis, 2018, vol. 44, pp. 72-85