A CNN-based methodology for breast cancer diagnosis using thermal images
FEMTO-ST institute（FEMTO-ST研究所）；Univ. Bourgogne Franche-Comté（勃艮第-弗朗什-孔泰大学）；CNRS（法国国家科学研究中心）；ENSMM（国立高等机械与微技术学院）；University of Oviedo（奥维耶多大学）；Universidad Autonoma del Caribe（加勒比自治大学）；Batna University（巴特纳大学）；University of Biskra（比斯克拉大学）
Juan Zuluaga-Gomez, Zeina Al Masry, Khaled Benaggoune, Safa Meraghni, Noureddine Zerhouni
备注：
19 pages, 7 figures, 5 tables. Clinical Breast Cancer
Micro Abstract: A recent study from GLOBOCAN disclosed that during 2018 two million women worldwide had been diagnosed from breast cancer. This study presents a computer-aided diagnosis system based on convolutional neural networks as an alternative diagnosis methodology for breast cancer diagnosis with thermal images. Experimental results showed that lower false-positives and false-negatives classification rates are obtained when data pre-processing and data augmentation techniques are implemented in these thermal images. Background: There are many types of breast cancer screening techniques such as, mammography, magnetic resonance imaging, ultrasound and blood sample tests, which require either, expensive devices or personal qualified. Currently, some countries still lack access to these main screening techniques due to economic, social or cultural issues. The objective of this study is to demonstrate that computer-aided diagnosis(CAD) systems based on convolutional neural networks (CNN) are faster, reliable and robust than other techniques. Methods: We performed a study of the influence of data pre-processing, data augmentation and database size versus a proposed set of CNN models. Furthermore, we developed a CNN hyper-parameters fine-tuning optimization algorithm using a tree parzen estimator. Results: Among the 57 patients database, our CNN models obtained a higher accuracy (92\%) and F1-score (92\%) that outperforms several state-of-the-art architectures such as ResNet50, SeResNet50 and Inception. Also, we demonstrated that a CNN model that implements data-augmentation techniques reach identical performance metrics in comparison with a CNN that uses a database up to 50\% bigger. Conclusion: This study highlights the benefits of data augmentation and CNNs in thermal breast images. Also, it measures the influence of the database size in the performance of CNNs.
Stony Brook University（石溪大学）；Stony Brook Medicine（石溪医学院）；Stony Brook University Hospital（石溪大学医院）；University of Michigan Medical School（密歇根大学医学院）；National Cancer Institute（美国国家癌症研究所）；National Institutes of Health（美国国立卫生研究院）；Emory University（埃默里大学）
Quantitative assessment of Tumor-TIL spatial relationships is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network (CNN) analysis pipelines to generate combined maps of cancer regions and tumor infiltrating lymphocytes (TILs) in routine diagnostic breast cancer whole slide tissue images (WSIs). We produce interactive whole slide maps that provide 1) insight about the structural patterns and spatial distribution of lymphocytic infiltrates and 2) facilitate improved quantification of TILs. We eva…
This paper presents results of applying Inception v4 deep convolutional neural network to ICIAR-2018 Breast Cancer Classification Grand Challenge, part a. The Challenge task is to classify breast cancer biopsy results, presented in form of hematoxylin and eosin stained images. Breast cancer classification is of primary interest to the medical practitioners and thus binary classification of breast cancer images have been under investigation by many researchers, but multi-class categorization of histology breast images have been challenging due to the subtle differences among the categories. In …
Traditional breast cancer image classification methods require manual extraction of features from medical images, which not only require professional medical knowledge, but also have problems such as time-consuming and labor-intensive and difficulty in extracting high-quality features. Therefore, the paper proposes a computer-based feature fusion Convolutional neural network breast cancer image classification and detection method. The paper pre-trains two convolutional neural networks with different structures, and then uses the convolutional neural network to automatically extract the charact…
Generally, human epidermal growth factor 2 (HER2) breast cancer is more aggressive than other kinds of breast cancer. Currently, HER2 breast cancer is detected using expensive medical tests are most expensive. Therefore, the aim of this study was to develop a computational model named convoHER2 for detecting HER2 breast cancer with image data using convolution neural network (CNN). Hematoxylin and eosin (H&E) and immunohistochemical (IHC) stained images has been used as raw data from the Bayesian information criterion (BIC) benchmark dataset. This dataset consists of 4873 images of H&E and IHC…
Breast cancer is the most common cancer among women both in developed and developing countries. Early detection and diagnosis of breast cancer may reduce its mortality and improve the quality of life. Computer-aided detection (CADx) and computer-aided diagnosis (CAD) techniques have shown promise for reducing the burden of human expert reading and improve the accuracy and reproducibility of results. Sparse analysis techniques have produced relevant results for representing and recognizing imaging patterns. In this work we propose a method for Label Consistent Spatially Localized Ensemble Spars…
Deep Learning in Breast Cancer Imaging: A Decade of Progress and Future Directions
The Hong Kong University of Science and Technology（香港科技大学）；Stanford University School of Medicine（斯坦福大学医学院）；The Chinese University of Hong Kong（香港中文大学）；The University of Hong Kong（香港大学）；HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute（香港科技大学深圳-香港协同创新研究院）
Umm Al-Qura University（乌姆·库拉大学）；King Abdulaziz University（阿卜杜勒阿齐兹国王大学）；University of Tabuk（塔布克大学）；King Faisal Specialist Hospital and Research Center（费萨尔国王专科医院和研究中心）；University of Nevada（内华达大学）
Breast cancer is the most common cancer in the world and the second most common type of cancer that causes death in women. The timely and accurate diagnosis of breast cancer using histopathological images is crucial for patient care and treatment. Pathologists can make more accurate diagnoses with the help of a novel approach based on image processing. This approach is an ensemble model of two types of pre-trained vision transformer models, namely, Vision Transformer and Data-Efficient Image Transformer. The proposed ensemble model classifies breast cancer histopathology images into eight clas…
South China University of Technology（华南理工大学）；Guangdong Provincial People’s Hospital（广东省人民医院）；Guangdong Academy of Medical Sciences（广东省医学科学院）
Ultrasonography is an important routine examination for breast cancer diagnosis, due to its non-invasive, radiation-free and low-cost properties. However, the diagnostic accuracy of breast cancer is still limited due to its inherent limitations. It would be a tremendous success if we can precisely diagnose breast cancer by breast ultrasound images (BUS). Many learning-based computer-aided diagnostic methods have been proposed to achieve breast cancer diagnosis/lesion classification. However, most of them require a pre-define ROI and then classify the lesion inside the ROI. Conventional classif…
Jalpaiguri Government Engineering College（贾尔派古里政府工程学院）
Invasive ductal carcinoma (IDC), which is also sometimes known as the infiltrating ductal carcinoma, is the most regular form of breast cancer. It accounts for about 80% of all breast cancers. According to the American Cancer Society, more than 180,000 women in the United States are diagnosed with invasive breast cancer each year. The survival rate associated with this form of cancer is about 77% to 93% depending on the stage at which they are being diagnosed. The invasiveness and the frequency of the occurrence of these disease makes it one of the difficult cancers to be diagnosed. Our propos…
Cancer is one of the most common and fatal diseases in the world. Breast cancer affects one in every eight women and one in every eight hundred men. Hence, our prime target should be early detection of cancer because the early detection of cancer can be helpful to cure cancer effectively. Therefore, we propose a saliency detection system with the help of advanced deep learning techniques, such that the machine will be taught to emulate actions of pathologists for localization of diagnostically pertinent regions. We study identification of five diagnostic categories of breast cancer by training…
Breast cancer is one of the most common cancer in women around the world. For diagnosis, pathologists evaluate biomarkers such as HER2 protein using immunohistochemistry over tissue extracted by a biopsy. Through microscopic inspection, this assessment estimates the intensity and integrity of the membrane cells' staining and scores the sample as 0, 1+, 2+, or 3+: a subjective decision that depends on the interpretation of the pathologist. This paper presents the preliminary data analysis of the annotations of three pathologists over the same set of samples obtained using 20x magnification and …
Mansoura University（曼苏拉大学）；Higher Institute of Engineering and Technology（高等工程技术学院）
Breast cancer is one of the most serious types of cancer that can occur in women. The automatic diagnosis of breast cancer by analyzing histological images (HIs) is important for patients and their prognosis. The classification of HIs provides clinicians with an accurate understanding of diseases and allows them to treat patients more efficiently. Deep learning (DL) approaches have been successfully employed in a variety of fields, particularly medical imaging, due to their capacity to extract features automatically. This study aims to classify different types of breast cancer using HIs. In th…
Military Institute of Science and Technology (MIST)（军事科学技术学院）
Breast cancer is the second most responsible for all cancer types and has been the cause of numerous deaths over the years, especially among women. Any improvisation of the existing diagnosis system for the detection of cancer can contribute to minimizing the death ratio. Moreover, cancer detection at an early stage has recently been a prime research area in the scientific community to enhance the survival rate. Proper choice of machine learning tools can ensure early-stage prognosis with high accuracy. In this paper, we have studied different machine learning algorithms to detect whether a pa…
University of Idaho（爱达荷大学）；Harbin Institute of Technology（哈尔滨工业大学）；Medical College at Qingdao University（青岛大学医学院）
Deep learning-based computer-aided diagnosis has achieved unprecedented performance in breast cancer detection. However, most approaches are computationally intensive, which impedes their broader dissemination in real-world applications. In this work, we propose an efficient and light-weighted multitask learning architecture to classify and segment breast tumors simultaneously. We incorporate a segmentation task into a tumor classification network, which makes the backbone network learn representations focused on tumor regions. Moreover, we propose a new numerically stable loss function that e…
University of Kentucky（肯塔基大学）；Miami University（迈阿密大学）
Breast cancer is the malignant tumor that causes the highest number of cancer deaths in females. Digital mammograms (DM or 2D mammogram) and digital breast tomosynthesis (DBT or 3D mammogram) are the two types of mammography imagery that are used in clinical practice for breast cancer detection and diagnosis. Radiologists usually read both imaging modalities in combination; however, existing computer-aided diagnosis tools are designed using only one imaging modality. Inspired by clinical practice, we propose an innovative convolutional neural network (CNN) architecture for breast cancer classi…
University of Delaware（特拉华大学）；Amazon Web Services（亚马逊云科技）；University of Rochester（罗切斯特大学）
Objective and Impact Statement. We adopt a deep learning model for bone osteolysis prediction on computed tomography (CT) images of murine breast cancer bone metastases. Given the bone CT scans at previous time steps, the model incorporates the bone-cancer interactions learned from the sequential images and generates future CT images. Its ability of predicting the development of bone lesions in cancer-invading bones can assist in assessing the risk of impending fractures and choosing proper treatments in breast cancer bone metastasis. Introduction. Breast cancer often metastasizes to bone, cau…
University of Saskatchewan（萨斯喀彻温大学）；University of Tulane（杜兰大学）
Breast cancer is one of the most common causes of cancer-related death in women worldwide. Early and accurate diagnosis of breast cancer may significantly increase the survival rate of patients. In this study, we aim to develop a fully automatic, deep learning-based, method using descriptor features extracted by Deep Convolutional Neural Network (DCNN) models and pooling operation for the classification of hematoxylin and eosin stain (H&E) histological breast cancer images provided as a part of the International Conference on Image Analysis and Recognition (ICIAR) 2018 Grand Challenge on BreAs…
University of Malaya（马来亚大学）；University of Tehran（德黑兰大学）
Reliable classification of benign and malignant lesions in breast ultrasound images can provide an effective and relatively low cost method for early diagnosis of breast cancer. The accuracy of the diagnosis is however highly dependent on the quality of the ultrasound systems and the experience of the users (radiologists). The leverage in deep convolutional neural network approaches provided solutions in efficient analysis of breast ultrasound images. In this study, we proposed a new framework for classification of breast cancer lesions by use of an attention module in modified VGG16 architect…
FECT: Classification of Breast Cancer Pathological Images Based on Fusion Features
Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School（清华深圳国际研究生院生物制药与健康工程研究所）；School of Medicine, Nankai University（南开大学医学院）
The Chinese University of Hong Kong（香港中文大学）；Imsight Medical Technology, Co., Ltd.（推想医疗科技股份有限公司）；Imperial College London（伦敦帝国理工学院）；The Fifth Medical Center of Chinese PLA General Hospital（中国人民解放军总医院第五医学中心）；Beijing Image Diagnostic Center of Rimag（北京一脉阳光影像诊断中心）
Accurate and automatic analysis of breast MRI plays an important role in early diagnosis and successful treatment planning for breast cancer. Due to the heterogeneity nature, accurate diagnosis of tumors remains a challenging task. In this paper, we propose to identify breast tumor in MRI by Cosine Margin Sigmoid Loss (CMSL) with deep learning (DL) and localize possible cancer lesion by COrrelation Attention Map (COAM) based on the learned features. The CMSL embeds tumor features onto a hypersphere and imposes a decision margin through cosine constraints. In this way, the DL model could learn …
Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related death among females worldwide. In this article, we investigate the applicability of densely connected convolutional neural networks to the problems of histology image classification and whole slide image segmentation in the area of computer-aided diagnoses for breast cancer. To this end, we study various approaches for transfer learning and apply them to the data set from the 2018 grand challenge on breast cancer histology images (BACH).
New York University（纽约大学）；New York University School of Medicine（纽约大学医学院）
We trained and evaluated a localization-based deep CNN for breast cancer screening exam classification on over 200,000 exams (over 1,000,000 images). Our model achieves an AUC of 0.919 in predicting malignancy in patients undergoing breast cancer screening, reducing the error rate of the baseline (Wu et al., 2019a) by 23%. In addition, the models generates bounding boxes for benign and malignant findings, providing interpretable predictions.
DeepHealth, Inc.（深健公司）；Rhode Island Hospital（罗德岛医院）；Brown University（布朗大学）；Henan Provincial People’s Hospital（河南省人民医院）；Medford Radiology Group（梅德福放射学集团）；University of Massachusetts Medical School（马萨诸塞大学医学院）
Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data p…
Breast cancer is the second most common malignancy among women and has become a major public health problem in current society. Traditional breast cancer identification requires experienced pathologists to carefully read the breast slice, which is laborious and suffers from inter-observer variations. Consequently, an automatic classification framework for breast cancer identification is worthwhile to develop. Recent years witnessed the development of deep learning technique. Increasing number of medical applications start to use deep learning to improve diagnosis accuracy. In this paper, we pr…
University of Pennsylvania（宾夕法尼亚大学）；Mayo Clinic（梅奥诊所）
Breast density is an important risk factor for breast cancer that also affects the specificity and sensitivity of screening mammography. Current federal legislation mandates reporting of breast density for all women undergoing breast screening. Clinically, breast density is assessed visually using the American College of Radiology Breast Imaging Reporting And Data System (BI-RADS) scale. Here, we introduce an artificial intelligence (AI) method to estimate breast percentage density (PD) from digital mammograms. Our method leverages deep learning (DL) using two convolutional neural network arch…
Towards Early Detection: AI-Based Five-Year Forecasting of Breast Cancer Risk Using Digital Breast Tomosynthesis Imaging
Athinoula A. Martinos Center for Biomedical Imaging, Mass General Brigham and Harvard Medical School（Athinoula A. Martinos 生物医学成像中心，马萨诸塞总医院与哈佛医学院）；École Polytechnique Fédérale de Lausanne (EPFL)（洛桑联邦理工学院）；Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin（柏林夏里特医学院，自由大学和洪堡大学的成员）；Department of Radiology, University of Wisconsin School of Medicine and Public Health（威斯康星大学医学与公共卫生学院放射科）
This paper presents U-net based breast cancer metastases detection and classification in lymph nodes, as well as patient-level classification based on metastases detection. The whole pipeline can be divided into five steps: preprocessing and data argumentation, patch-based segmentation, post processing, slide-level classification, and patient-level classification. In order to reduce overfitting and speedup convergence, we applied batch normalization and dropout into U-Net. The final Kappa score reaches 0.902 on training data.
Department of Electrical and Electronics Engineering, Shiraz University of Technology（设拉子理工大学电气与电子工程系）；Department of Pathology, School of Medicine, Shiraz University of Medical Sciences（设拉子医科大学医学院病理学系）
Early detection and prognosis of breast cancer are feasible by utilizing histopathological grading of biopsy specimens. This research is focused on detection and grading of nuclear pleomorphism in histopathological images of breast cancer. The proposed method consists of three internal steps. First, unmixing colors of H&E is used in the preprocessing step. Second, nuclei boundaries are extracted incorporating the center of cancerous nuclei which are detected by applying morphological operations and Difference of Gaussian filter on the preprocessed image. Finally, segmented nuclei are scored to…
East Delta University（东三角洲大学）；University of Chittagong（吉大港大学）
Breast cancer has become a symbol of tremendous concern in the modern world, as it is one of the major causes of cancer mortality worldwide. In this regard, breast ultrasonography images are frequently utilized by doctors to diagnose breast cancer at an early stage. However, the complex artifacts and heavily noised breast ultrasonography images make diagnosis a great challenge. Furthermore, the ever-increasing number of patients being screened for breast cancer necessitates the use of automated end-to-end technology for highly accurate diagnosis at a low cost and in a short time. In this conce…
McGill University（麦吉尔大学）；Mila Quebec AI Institute（米拉魁北克人工智能研究所）；Lelapa AI（莱拉帕人工智能）；Masakhane Research Foundation（马萨卡内研究基金会）；Drexel University（德雷塞尔大学）；University Of Maryland Baltimore County（马里兰大学巴尔的摩县分校）
Cancer is increasingly a global health issue. Seconding cardiovascular diseases, cancers are the second biggest cause of death in the world with millions of people succumbing to the disease every year. According to the World Health Organization (WHO) report, by the end of 2020, more than 7.8 million women have been diagnosed with breast cancer, making it the world's most prevalent cancer. In this paper, using the Nightingale Open Science dataset of digital pathology (breast biopsy) images, we leverage the capabilities of pre-trained computer vision models for the breast cancer stage prediction…
Breast Cancer Image Classification Method Based on Deep Transfer Learning
The Hong Kong University of Science and Technology（香港科技大学）；University of Southampton（南安普顿大学）；Trine University（特莱恩大学）；Southwest Jiaotong University（西南交通大学）
Breast cancer is a disease that threatens many women's life, thus, early and accurate detection plays a key role in reducing the mortality rate. Mammography stands as the reference technique for breast cancer screening; nevertheless, many countries still lack access to mammograms due to economic, social, and cultural issues. Last advances in computational tools, infrared cameras, and devices for bio-impedance quantification allowed the development of parallel techniques like thermography, infrared imaging, and electrical impedance tomography, these being faster, reliable and cheaper. In the la…
Shenzhen University（深圳大学）；Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University（中山大学孙逸仙纪念医院）
Breast cancer is one of the leading causes of cancer deaths in women. As the primary output of breast screening, breast ultrasound (US) video contains exclusive dynamic information for cancer diagnosis. However, training models for video analysis is non-trivial as it requires a voluminous dataset which is also expensive to annotate. Furthermore, the diagnosis of breast lesion faces unique challenges such as inter-class similarity and intra-class variation. In this paper, we propose a pioneering approach that directly utilizes US videos in computer-aided breast cancer diagnosis. It leverages ma…
Breast cancer (BC) is the most common cancer among women world-wide, approximately 20-25% of BCs are HER-2 positive. Analysis of HER-2 is fundamental to defining the appropriate therapy for patients with breast cancer. Inter-pathologist variability in the test results can affect diagnostic accuracy. The present study intends to propose an automatic scoring HER-2 algorithm. Based on color features, the technique is fully-automated and avoids segmentation, showing a concordance higher than 90% with a pathologist in the experiments realized.
The Deep Convolutional Neural Network (DCNN) is one of the most powerful and successful deep learning approaches. DCNNs have already provided superior performance in different modalities of medical imaging including breast cancer classification, segmentation, and detection. Breast cancer is one of the most common and dangerous cancers impacting women worldwide. In this paper, we have proposed a method for breast cancer classification with the Inception Recurrent Residual Convolutional Neural Network (IRRCNN) model. The IRRCNN is a powerful DCNN model that combines the strength of the Inception…
École de Technologie Supérieure, Université du Québec（魁北克大学高等技术学院）；Université de Rouen Normandie（鲁昂诺曼底大学）
Breast cancer is one of the most common types of cancer and leading cancer-related death causes for women. In the context of ICIAR 2018 Grand Challenge on Breast Cancer Histology Images, we compare one handcrafted feature extractor and five transfer learning feature extractors based on deep learning. We find out that the deep learning networks pretrained on ImageNet have better performance than the popular handcrafted features used for breast cancer histology images. The best feature extractor achieves an average accuracy of 79.30%. To improve the classification performance, a random forest di…
Cancer is one of the most dangerous diseases to humans, and yet no permanent cure has been developed for it. Breast cancer is one of the most common cancer types. According to the National Breast Cancer foundation, in 2020 alone, more than 276,000 new cases of invasive breast cancer and more than 48,000 non-invasive cases were diagnosed in the US. To put these figures in perspective, 64% of these cases are diagnosed early in the disease's cycle, giving patients a 99% chance of survival. Artificial intelligence and machine learning have been used effectively in detection and treatment of severa…
Friedrich-Alexander-Universität Erlangen-Nürnberg（弗里德里希-亚历山大大学埃尔兰根-纽伦堡分校）；Freie Universität Berlin（柏林自由大学）；Animal Medical Center（动物医学中心）
Canine mammary carcinoma (CMC) has been used as a model to investigate the pathogenesis of human breast cancer and the same grading scheme is commonly used to assess tumor malignancy in both. One key component of this grading scheme is the density of mitotic figures (MF). Current publicly available datasets on human breast cancer only provide annotations for small subsets of whole slide images (WSIs). We present a novel dataset of 21 WSIs of CMC completely annotated for MF. For this, a pathologist screened all WSIs for potential MF and structures with a similar appearance. A second expert blin…
Traditional breast cancer imaging methods using microwave Nearfield Radar Imaging (NRI) seek to recover the complex permittivity of the tissues at each voxel in the imaging region. This approach is suboptimal, in that it does not directly consider the permittivity values that healthy and cancerous breast tissues typically have. In this paper, we describe a novel unmixing algorithm for detecting breast cancer. In this approach, the breast tissue is separated into three components, low water content (LWC), high water content (HWC), and cancerous tissues, and the goal of the optimization procedur…
Characterization of breast parenchyma on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging task owing to the complexity of underlying tissue structures. Current quantitative approaches, including radiomics and deep learning models, do not explicitly capture the complex and subtle parenchymal structures, such as fibroglandular tissue. In this paper, we propose a novel method to direct a neural network's attention to a dedicated set of voxels surrounding biologically relevant tissue structures. By extracting multi-dimensional topological structures with high salienc…
University of Minnesota（明尼苏达大学）；University of Cincinnati（辛辛那提大学）
Image classification is widely used to build predictive models for breast cancer diagnosis. Most existing approaches overwhelmingly rely on deep convolutional networks to build such diagnosis pipelines. These model architectures, although remarkable in performance, are black-box systems that provide minimal insight into the inner logic behind their predictions. This is a major drawback as the explainability of prediction is vital for applications such as cancer diagnosis. In this paper, we address this issue by proposing an explainable machine learning pipeline for breast cancer diagnosis base…
Faculty of Informatics and Computer Science（信息与计算机科学学院）；The British University in Egypt（埃及英国大学）；Faculty of Science, Suez Canal University（苏伊士运河大学理学院）
Breast cancer is one of the leading fatal disease worldwide with high risk control if early discovered. Conventional method for breast screening is x-ray mammography, which is known to be challenging for early detection of cancer lesions. The dense breast structure produced due to the compression process during imaging lead to difficulties to recognize small size abnormalities. Also, inter- and intra-variations of breast tissues lead to significant difficulties to achieve high diagnosis accuracy using hand-crafted features. Deep learning is an emerging machine learning technology that requires…
