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Deep convolution neural network for screening carotid calcification in dental panoramic radiographs [1]

['Moshe Amitay', 'Odmachine Ltd.', 'Herzliya', 'Bioinformatic Department', 'Jerusalem College Of Technology', 'Jerusalem', 'Zohar Barnett-Itzhaki', 'Faculty Of Engineering', 'Ruppin Academic Center', 'Emek Hefer']

Date: 2023-05 

Abstract Ischemic stroke, a leading global cause of death and disability, is commonly caused by carotid arteries atherosclerosis. Carotid artery calcification (CAC) is a well-known marker of atherosclerosis. Such calcifications are classically detected by ultrasound screening. In recent years it was shown that these calcifications can also be inferred from routine panoramic dental radiographs. In this work, we focused on panoramic dental radiographs taken from 500 patients, manually labelling each of the patients’ sides (each radiograph was treated as two sides), which were used to develop an artificial intelligence (AI)-based algorithm to automatically detect carotid calcifications. The algorithm uses deep learning convolutional neural networks (CNN), with transfer learning (TL) approach that achieved true labels for each corner, and reached a sensitivity (recall) of 0.82 and a specificity of 0.97 for individual arteries, and a recall of 0.87 and specificity of 0.97 for individual patients. Applying and integrating the algorithm in healthcare units and dental clinics has the potential of reducing stroke events and their mortality and morbidity consequences.

Author summary Stroke is a leading global cause of death and disability. One major cause of stroke is carotid arteries atherosclerosis. Carotid artery calcification (CAC) is a well-known marker of atherosclerosis. Traditional approaches for CAC detection are doppler ultrasound screening and angiography computerized tomography (CT), medical procedures that incur financial expenses, and are time consuming and discomforting to the patient. Of note, angiography CT involves the injection of contrast material and exposure to X-ray ionizing irradiation. In recent years researchers have shown that CAC can also be detected by analyzing routine panoramic dental radiographs, a non-invasive, cheap and easily accessible procedure. This study takes us one step further, in developing artificial intelligence (AI)-based algorithms trained to detect such calcifications in panoramic dental radiographs. The models developed are based on deep learning convolutional neural networks and transfer learning, that enable an accurate automated detection of carotid calcifications, with a recall of 0.82 and a specificity of 0.97. Statistical approaches for assessing predictions per individual (i.e.: predicting the risk of calcification in at least one artery) were developed, showing a recall of 0.87 and specificity of 0.97. Applying and integrating this approach in healthcare units may significantly contribute to identifying at-risk patients.

Citation: Amitay M, Barnett-Itzhaki Z, Sudri S, Drori C, Wase T, Abu-El-Naaj I, et al. (2023) Deep convolution neural network for screening carotid calcification in dental panoramic radiographs. PLOS Digit Health 2(4): e0000081. https://doi.org/10.1371/journal.pdig.0000081 Editor: Bo Wang, University of Toronto, CANADA Received: June 30, 2022; Accepted: March 13, 2023; Published: April 12, 2023 Copyright: © 2023 Amitay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: Relevant data set is provided in the manuscript and in the supplementary. Further data cannot be shared publicly as they contain potentially identifying patient information. The data are owned by Poriya hospital. For researchers who meet the criteria for access to confidential data, requests for these data sets can be sent to zohar@odmachine.com. The authors had no special access privileges that others would not have. Funding: The computational parts of the study were conducted by a commercial company (ODMachine LTD). The authors received no specific funding for this work. Competing interests: I have read the journal’s policy. Most authors are advisors to or employees of a commercial company. SS and IAEN are not employees of a commercial company and don’t have any competing interests.

Introduction Stroke is the third leading cause of death and the leading cause of disability in the Western world. Ischemic stroke is caused by carotid arteries atherosclerosis, small intracranial vessel disease or emboli from the heart and aorta [1,2]. The lifelong risk of stroke in adult men and women (age 25 and older) is about 25 percent [3]. Ten percent of strokes are caused by intracerebral hemorrhage and 87% of all strokes are ischemic [2]. Several studies showed that patients aged 60–96 with carotid artery calcification (CAC) found in panoramic radiograph are 2.4 fold more likely to suffer from vascular events, including stroke and/or ischemic heart diseases [4,5]. Although evidence for the predictive value of CAC is still variable, as reviewed by Lim et al, it is established as useful for identifying at risk patients and referral for further evaluation [6]. Standard tests for detecting CAC are doppler ultrasound (US) and angiography computerized tomography (CT). However, there is evidence that calcification can be detected in panoramic dental X-rays (dental radiographs) [7–11]. These X-rays are routinely performed in daily practice by dentists and oral and maxillofacial surgeons. A panoramic radiograph is a two-dimensional interpretation of tomographic images of curved anatomic structures. Panoramic radiography images serve as a diagnostic tool, and the image encompasses the teeth, the maxillary and mandibular bones, temporomandibular joints, and the maxillary sinus. Nonetheless, most dental professionals, dentists as well as specialists, are not trained for detecting and diagnosing CAC in panoramic X rays. Several studies focused on evaluating the ability of panoramic radiographs to detect CAC [5] and showed the potential in the use of panoramic radiographs to help identify at-risk patients who require further evaluation [8]. Recent meta-analyses of these studies revealed that the level of agreement between panoramic radiography and the above standard methods is 50% [12]. However, even with this limitation, panoramic radiography is more prevalent by far than US or coronary angiography (CAG). The panoramic radiograph has a sensitivity of 66.6% and a positive predictive value of 45% for detecting carotid artery calcifications in patients whose angiograms confirmed coronary artery disease [13]. Therefore, panoramic radiography may play an important role in the screening and detection of non-symptomatic CAC patients in the population. Deep neural networks are a branch of machine learning (ML) and artificial intelligence (AI). Deep learning algorithms use architectures that are composed of multiple artificial neurons to form neural networks (NN) that can predict a value/class for new samples. These architectures were developed to tackle complex challenges such as speech recognition, natural language processing, image classification and object recognition [14]. Deep learning architectures and algorithms use multilayer artificial neural network (NN) architecture. A major class of deep learning algorithms is the convolutional neural networks (CNN), that are widely used for image classification [15]. In order to cope with potential biases and to produce the most efficient networks, it may be advisable to optimize the convolution neural networks [16]. Major challenges in the development of an efficient CNN classifier are the requirement for large numbers of training samples (usually >1,000 for each class), and a long and comprehensive process of model training. In order to cope with these challenges, the transfer learning (TL) approach was developed. In this approach, the CNN training is not created from scratch, but uses an existing pre-trained model as a starting point [17,18]. The pre-trained model was previously trained on a different task using huge amounts of data. CNN and TL have been widely used in the prediction of medical conditions using different techniques (CT, MRI, panoramic images)–for example: identification of prostate cancer [19]; prediction of bladder cancer treatment response in CT [20]; detection of maxillary sinusitis on panoramic radiographs [21]; screening for osteoporosis in dental panoramic radiographs (DPR) [22]; cardiac cine segmentation [23] and even COVID-19 detection from chest CT-scans [24]. Furthermore, Kats et al. have recently shown the potential of applying CNN to detect CAC, using Faster Region-based Convolutional Neural Network (FR-CNN) [25] on a modest set of 65 DPRs reaching a F1 score of 0.77 [26]. In this study we aimed to develop and evaluate a robust image classifier for screening carotid calcification (CAC) in standard (DPR) images using a relatively large cohort of hundreds of DPRs, utilizing advanced approaches. The benchmark in this study was the human annotations of CAC in a panoramic radiograph. We trained and tested a convolutional neural network (CNN) based on transfer learning for CAC detection of a single carotid (one side of the image) and then calculated the performance of a full panoramic radiography images. Our algorithm reached good performances of recall of 0.87 and specificity of 0.97.

Discussion Prediction of stroke is still one of the major challenges in western medicine. Atherosclerosis of the carotid arteries is an important etiology for ischemic stroke. The main risk factors for atherosclerosis are hypertension, diabetes, hyperlipidemia, high cholesterol levels, smoking and obesity, all of which cause endothelial cell dysfunction. Atherosclerosis tends to calcify over the years. Therefore, carotid artery calcification is a manifestation of advanced atherosclerosis in the carotid arteries as well as a marker for atherosclerosis in other blood vessels, including coronary artery disease and peripheral vascular disease in the lower extremities. Early diagnosis of carotid arteries calcification (atherosclerosis) would prevent stroke by diagnosing, monitoring and treating carotid arteries stenoses as well as detecting and treating risk. Carotid calcifications can be detected by performing a carotid ultrasound screening, but this is not a routine procedure, and is usually recommended only when a murmur is detected on auscultation or upon evidence of lower limb peripheral vascular disease, or in the presence of medical conditions that increase the risk of stroke. Periodic ultrasound screenings of the carotid arteries could detect carotid arteries atherosclerosis and calcification before the appearance of clinical manifestation; however, such a policy would involve a huge financial burden and is thus impractical. CT angiography is another test that detects atherosclerosis and calcification in carotid arteries. It involves the injection of contrast material and exposure to X-ray ionizing irradiation which, in addition to significant financial expenses, make this test inadequate for screening purposes. Panoramic dental X-rays may provide important information on carotid artery calcification [26,38,39]. They are performed routinely and the information on possible CAC can be retrieved without additional clinical test or procedure. In this work we developed an AI-based algorithm that can efficiently diagnose calcified atherosclerosis in the carotid arteries, using routine panoramic dental X-rays images. Such diagnosis once available, should direct the treating physician to refer the patient for further evaluation and treatment of carotid artery narrowing, and indicates risk factors for atherosclerosis in various blood vessels, including those causing coronary artery disease and peripheral vascular disease of the lower limbs. The first challenge in this study is the absence of a typical constant structure to the signs of calcification, i.e. there are no general characteristics of CAC that provide common range of shapes and orientations. Additionally, this region in the panoramic images contains background noise and other organs/bones, including the hyoid bone and various shapes of the spinal cord. One approach we used to cope with this challenge was through TL, that was successfully implemented in previous medical studies, including AI-based studies that analyzed panoramic radiographs [21,22]. An earlier study presented a computer-aided rule-based approach for detecting carotid calcification in panoramic radiographs using grayscale gradients and top-hat filters [40]. More recent studies have employed Faster Region-based Convolutional Neural Network (Faster R-CNN) [25] to detect carotid calcification in panoramic radiographs. Kats et al. [26] reported a sensitivity of 75%, specificity of 80%, and accuracy of 83%. Song et al. presented AI-based detection of three soft tissue diseases, including carotid artery calcification, using faster R-CNN on panoramic images, reporting a sensitivity of 77.4% and specificity of 71.4% for CAC detection [41]. Computer aided screening of calcification in radiological images is not specific only to the current challenge. There are other procedures in which it can be adopted, such as for detecting coronary calcification in intravascular Optical Coherence Tomography (OCT) and detecting calcifications in breast mammograms. Several studies aimed to computationally screen calcifications using AI and CNN approaches have been published: Li et al. used CNN to automate the segmentation and quantify coronary calcification in intravascular OCT images, reaching a F1 score of 0.96 [42]; Fuhrman et al. developed an algorithm based on both CNN Support Vector Machine (SVM) algorithm to classify coronary artery calcifications in low dose thoracic CT [43]. Other studies used a variety of deep neural network approaches based on CT images to predict different pathologies, such as transcatheter aortic valve replacement [44], chemotherapy response in breast cancer [45], quantitative assessment of liver trauma [46], and even the evaluation of complications associated with metastatic spine tumor surgery [47]. Panoramic radiographs are a routine part of oral and maxillofacial examinations. The high number of panoramic X rays performed routinely in dental clinics can provide an important and efficient source for the early detection of calcifications. Nevertheless, the inadequate training and awareness of dental personnel in detecting pathologies of the neck region, especially carotid artery calcifications, results in the ignoring of vast amounts of available information that has a high potential for the diagnosis, prevention, and monitoring of atherosclerotic changes in the carotid arteries. We believe that the current study lays the foundation for a valuable clinical tool aimed at providing health professionals with information for referring patients to an appropriate specialist. This novel clinical tool may be used on a wide basis in healthcare organizations, both dental and medical. The present study has several limitations. Manual labeling (by a physician) is challenging: CACs can be confused with other soft tissue calcifications in the same radiologic region, such as the triticeous cartilage calcification. Finally, it is not possible to make a conclusive diagnosis without doppler ultrasonography, which is used as the gold standard for the diagnosis of atherosclerosis [26]. Because of the retrospective design of this present study, doppler ultrasonographic screening could not be used as a reference. Another potential limitation is what seems as the relatively small population that could have led to overfitting. To tackle this potential limitation, we performed structural optimization, applied additional networks, and used augmentation. Furthermore, a sample size determination analysis showed that the sample size is sufficient. A possible additional limitation may be that the data does not representative of the overall population, mostly due to the relatively high proportions of the elderly (which are in any case more susceptible to strokes), or the fact that the method of diagnosing carotid artery calcification relies on expert diagnosis and not on other laboratory examinations. In addition, Error analysis revealed that at times, CNN failed to differentiate the triticeous from the CAC (of note, the two structures are very similar), leading to lower success rates. Adding additional triticeous images to the database may contribute to a better classification and differentiate between triticeous and CAC, leading to improved performance. We intend to conduct further research that will compare machine diagnosis to carotid ultrasound and angio-CT. We anticipate that a larger sample would improve this parameter. However, this study has significant strengths and benefits, including good AI performance, resulting in high recall (0.87) and substantial specificity (0.97), the ability to assess the algorithms’ performance for a patient, rather than just a corner, the repeatability of the results using different types of neural networks and structure. Above all, this study has the potential to provide clinics and healthcare organizations with a non-invasive, efficient, and applicable solution for the early detection of carotid calcification, both on a patient level and throughout healthcare systems. In summary, this study shows the potential and feasibility of applying deep learning-based methods in an actual “real-world” application of automatic screening for CAC in standard panoramic dental X-rays. Applying this approach may significantly contribute to quality of life of populations and save many lives.

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[1] Url: https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0000081

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