Despite coronary artery calcium scoring being considered a largely solved problem within the realm of medical artificial intelligence, this paper argues that significant improvements can still be made. By shifting the focus from pathology detection to a deeper understanding of anatomy, the novel algorithm proposed in the paper both achieves high accuracy in coronary artery calcium scoring and offers enhanced interpretability of the results. This approach not only aids in the precise quantification of calcifications in coronary arteries, but also provides valuable insights into the underlying anatomical structures. Through this anatomically-informed methodology, the paper shows how a nuanced understanding of the heart's anatomy can lead to more accurate and interpretable results in the field of cardiovascular health. We demonstrate the superior accuracy of the proposed method by evaluating it on an open-source multi-vendor dataset, where we obtain results at the inter-observer level, surpassing the current state of the art. Finally, the qualitative analyses show the practical value of the algorithm in such tasks as labeling coronary artery calcifications, identifying aortic calcifications, and filtering out false positive detections due to noise.

Background. Coronary artery calcium (CAC) is a powerful predictor of major adverse cardiovascular events (MACE). Traditional Agatston score simply sums the calcium, albeit in a non-linear way, leaving room for improved calcification assessments that will more fully capture the extent of disease. Objective. To determine if AI methods using detailed calcification features (i.e., calcium-omics) can improve MACE prediction. Methods. We investigated additional features of calcification including assessment of mass, volume, density, spatial distribution, territory, etc. We used a Cox model with elastic-net regularization on 2457 CT calcium score (CTCS) enriched for MACE events obtained from a large no-cost CLARIFY program (ClinicalTri-als.gov Identifier: NCT04075162). We employed sampling techniques to enhance model training. We also investigated Cox models with selected features to identify explainable high-risk characteristics. Results. Our proposed calcium-omics model with modified synthetic down sampling and up sampling gave C-index (80.5%/71.6%) and two-year AUC (82.4%/74.8%) for (80:20, training/testing), respectively (sampling was applied to the training set only). Results compared favorably to Agatston which gave C-index (71.3%/70.3%) and AUC (71.8%/68.8%), respectively. Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were important determinants of increased risk, with dense calcification (>1000HU) associated with lower risk. The calcium-omics model reclassified 63% of MACE patients to the high risk group in a held-out test. The categorical net-reclassification index was NRI=0.153. Conclusions. AI analysis of coronary calcification can lead to improved results as compared to Agatston scoring. Our findings suggest the utility of calcium-omics in improved prediction of risk.

Abstract--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 timeconsuming intermediateCAC 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. I. INTRODUCTION Cardiovascular disease (CVD) is the global leading cause of death [1]. To reduce the burden of cardiovascular disease the World Health Organization underlines the need for early detection and treatment of individuals with CVD or those who are at high cardiovascular risk due to the presence of one or more risk factors [2]. Quantification of CAC, i.e. calcium scoring, is typically performed in dedicated Personal use of this material is permitted. However, permission to use this material for any other purposes must be obtained from the IEEE by sending a request to pubs-permissions@ieee.org. Bob D. de Vos, Jelmer M. Wolterink, Nikolas Lessmann, and Ivana Išgum are with the Image Sciences Institute of the University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.