Cancer diagnosis using deep learning: A bibliographic review

In this paper, we first describe the basics of the field of cancer diagnosis, which includes steps of cancer diagnosis followed by the typical classification methods used by doctors, providing a historical idea of cancer classification techniques to the readers. These methods include Asymmetry, Border, Color and Diameter (ABCD) method, seven-point detection method, Menzies method, and pattern analysis. They are used regularly by doctors for cancer diagnosis, although they are not considered very efficient for obtaining better performance. Moreover, considering all types of audience, the basic evaluation criteria are also discussed. The criteria include the receiver operating characteristic curve (ROC curve), Area under the ROC curve (AUC), F1 score, accuracy, specificity, sensitivity, precision, dice-coefficient, average accuracy, and Jaccard index. Previously used methods are considered inefficient, asking for better and smarter methods for cancer diagnosis. Artificial intelligence and cancer diagnosis are gaining attention as a way to define better diagnostic tools. In particular, deep neural networks can be successfully used for intelligent image analysis. The basic framework of how this machine learning works on medical imaging is provided in this study, i.e., pre-processing, image segmentation and post-processing. The second part of this manuscript describes the different deep learning techniques, such as convolutional neural networks (CNNs), generative adversarial models (GANs), deep autoencoders (DANs), restricted Boltzmann’s machine (RBM), stacked autoencoders (SAE), convolutional autoencoders (CAE), recurrent neural networks (RNNs), long short-term memory (LTSM), multi-scale convolutional neural network (M-CNN), multi-instance learning convolutional neural network (MIL-CNN). For each technique, we provide Python codes, to allow interested readers to experiment with the cited algorithms on their own diagnostic problems. The third part of this manuscript compiles the successfully applied deep learning models for different types of cancers. Considering the length of the manuscript, we restrict ourselves to the discussion of breast cancer, lung cancer, brain cancer, and skin cancer. The purpose of this bibliographic review is to provide researchers opting to work in implementing deep learning and artificial neural networks for cancer diagnosis a knowledge from scratch of the state-of-the-art achievements

Computer-aided detection of lung nodules: A review

We present an in-depth review and analysis of salient methods for computer-aided detection of lung nodules. We evaluate the current methods for detecting lung nodules using literature searches with selection criteria based on validation dataset types, nodule sizes, numbers of cases, types of nodules, extracted features in traditional feature-based classifiers, sensitivity, and false positives (FP)/scans. Our review shows that current detection systems are often optimized for particular datasets and can detect only one or two types of nodules. We conclude that, in addition to achieving high sensitivity and reduced FP/scans, strategies for detecting lung nodules must detect a variety of nodules with high precision to improve the performances of the radiologists. To the best of our knowledge, ours is the first review of the effectiveness of feature extraction using traditional feature-based classifiers. Moreover, we discuss deep-learning methods in detail and conclude that features must be appropriately selected to improve the overall accuracy of the system. We present an analysis of current schemes and highlight constraints and future research areas

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

3D Lung Nodule Classification in Computed Tomography Images

Lung cancer is the leading cause of cancer death worldwide. One of the reasons is the absence of symptoms at an early stage, which means that it is only discovered at a later stage, where the treatment is more difficult [1]. Furthermore, when making a diagnosis, frequently done by reading computed tomographies (CT's), it is regularly allied with errors. One of the reasons is the variation of the opinion of the doctors regarding the diagnosis of the same nodule [2,3].The use of CADx, Computer-Aided Diagnosis, systems can be a great help for this problem by assisting doctors in diagnosis with a second opinion. Although its efficiency has already been proven [4], it often ends up not being used because doctors can not understand the "how and why" of CADx diagnostic results, and ultimately do not trust the system [5]. To increase the radiologists' confidence in the CADx system it is proposed that along with the results of malignancy prediction, there are also results with evidence that explains those malignancy results.There are some visible features in lung nodules that are correlated with malignancy. Since humans are able to visually identify these characteristics and correlate them with nodule malignancy, one way to present those evidence is to make predictions of those characteristics. To have these predictions it is proposed to use deep learning approaches. Convolutional neural networks had shown to outperform the state of the art results in medical image analysis [6]. To predict the characteristics and malignancy in CADx system, the architecture HSCNN, a deep hierarchical semantic convolutional neural network, proposed by Shen et al. [7], will be used.The Lung Image Database Consortium image collection (LIDC-IDRI) public dataset is frequently used as input for lung cancer CADx systems. The LIDC-IDRI consists of thoracic CT scans, presenting a lot of data's quantity and variability. In most of the nodules, this dataset has doctor's evaluations for 9 different characteristics. A recurrent problem in those evaluations is the subjectivity of the doctors' interpretation in what each characteristic is. In some characteristics, it can result in a great divergence in evaluations regarding the same nodule, which makes the inclusion of those evaluations as an input in CADx systems not useful as it could be. To reduce this subjectivity, it is proposed the creation of a metric that makes the characteristics classification more objective. For this, it is planned bibliographic and LIDC-IDRI dataset reviews. With that, taking into account this new metric, validated after by doctors from Hospital de São João, will be made a reclassification in LIDC-IDRI dataset. This way it could be possible to use as input all the relevant characteristics. The principal objective of this dissertation is to develop a lung nodule CADx system methodology which promotes the confidence of specialists in its use. This will be made classifying lung nodules according to relevant characteristics to diagnosis and malignancy. The reclassified LIDC-IDRI dataset will be used as an input for CADx system and the architecture used for predicting the characteristics and malignancy results will be the HSCNN. To measure the classification evaluation will be used sensitivity, sensibility, and area under the Receiver Operating Characteristic (ROC), curve. The proposed solution may be used for improving a CADx system, LNDetector, currently in development by the Center for Biomedical Engineering Research (C-BER) group from INESC-TEC in which this work will be developed.[1] - S. Sone M. Hasegawa and S. Takashima. Growth rate of small lung cancels detected on mass ct screening. Tire British Journal of Radiology, pages 1252-1259[2] - D. J. Bell S. E. Marley P. Guo H. Mann M. L. Scott L. H. Schwartz D. C. Ghiorghiu B. Zhao, Y. Tan. Exploring intra-and inter-reader variability in uni-dimensional, bi-dimensional, and volumetric measurements of solid tumors on ct scans reconstructed at different slice intervals. European journal of radiology 82, page 959-968, 2013[3] - H.T Winer-Muram. The solitary pulmonary nodule 1. Radiology, 239, pages 39-49, 2006.[4] - R. Yan J. Lee L. C. Chu C. T. Lin A. Hussien J. Rathmell B. Thomas C. Chen et al. P. Huang, S. Park. Added value of computer-aided ct image features for early lung cancer diagnosis with small pulmonary nodules: A matched case-control study. Radiology 286, page 286-295, 2017[5] - W Jorritsma, Fokie Cnossen, and Peter Van Ooijen. Improving the radiologist-cad interaction: Designing for appropriate trust. Clinical Radiology, 70, 10 2014.[6] - Tom Brosch, Youngjin Yoo, David Li, Anthony Traboulsee, and Roger Tam. Modeling the variability in brain morphology and lesion distribution in multiple sclerosis by deep learning. Volume 17, 09 2014.[7] - Simon Aberle Deni A. T. Bui Alex Hsu Willliam Shen, Shiwen X. Han. An interpretable deep hierarchical semantic convolutional neural network for lung nodule malignancy classification. june 201

Development of computer-based algorithms for unsupervised assessment of radiotherapy contouring

INTRODUCTION: Despite the advances in radiotherapy treatment delivery, target volume delineation remains one of the greatest sources of error in the radiotherapy delivery process, which can lead to poor tumour control probability and impact clinical outcome. Contouring assessments are performed to ensure high quality of target volume definition in clinical trials but this can be subjective and labour-intensive. This project addresses the hypothesis that computational segmentation techniques, with a given prior, can be used to develop an image-based tumour delineation process for contour assessments. This thesis focuses on the exploration of the segmentation techniques to develop an automated method for generating reference delineations in the setting of advanced lung cancer. The novelty of this project is in the use of the initial clinician outline as a prior for image segmentation. METHODS: Automated segmentation processes were developed for stage II and III non-small cell lung cancer using the IDEAL-CRT clinical trial dataset. Marker-controlled watershed segmentation, two active contour approaches (edge- and region-based) and graph-cut applied on superpixels were explored. k-nearest neighbour (k-NN) classification of tumour from normal tissues based on texture features was also investigated. RESULTS: 63 cases were used for development and training. Segmentation and classification performance were evaluated on an independent test set of 16 cases. Edge-based active contour segmentation achieved highest Dice similarity coefficient of 0.80 ± 0.06, followed by graphcut at 0.76 ± 0.06, watershed at 0.72 ± 0.08 and region-based active contour at 0.71 ± 0.07, with mean computational times of 192 ± 102 sec, 834 ± 438 sec, 21 ± 5 sec and 45 ± 18 sec per case respectively. Errors in accuracy of irregularly shaped lesions and segmentation leakages at the mediastinum were observed. In the distinction of tumour and non-tumour regions, misclassification errors of 14.5% and 15.5% were achieved using 16- and 8-pixel regions of interest (ROIs) respectively. Higher misclassification errors of 24.7% and 26.9% for 16- and 8-pixel ROIs were obtained in the analysis of the tumour boundary. CONCLUSIONS: Conventional image-based segmentation techniques with the application of priors are useful in automatic segmentation of tumours, although further developments are required to improve their performance. Texture classification can be useful in distinguishing tumour from non-tumour tissue, but the segmentation task at the tumour boundary is more difficult. Future work with deep-learning segmentation approaches need to be explored.Funded by National Radiotherapy Trials Quality Assurance (RTTQA) grou

Development and application in clinical practice of Computer-aided Diagnosis systems for the early detection of lung cancer

Lung cancer is the main cause of cancer-related deaths both in Europe and United States, because often it is diagnosed at late stages of the disease, when the survival rate is very low if compared to first asymptomatic stage. Lung cancer screening using annual low-dose Computed Tomography (CT) reduces lung cancer 5-year mortality by about 20% in comparison to annual screening with chest radiography. However, the detection of pulmonary nodules in low-dose chest CT scans is a very difficult task for radiologists, because of the large number (300/500) of slices to be analyzed. In order to support radiologists, researchers have developed Computer aided Detection (CAD) algorithms for the automated detection of pulmonary nodules in chest CT scans. Despite proved benefits of those systems on the radiologists detection sensitivity, the usage of CADs in clinical practice has not spread yet. The main objective of this thesis is to investigate and tackle the issues underlying this inconsistency. In particular, in Chapter 2 we introduce M5L, a fully automated Web and Cloud-based CAD for the automated detection of pulmonary nodules in chest CT scans. This system introduces a new paradigm in clinical practice, by making available CAD systems without requiring to radiologists any additional software and hardware installation. The proposed solution provides an innovative cost-effective approach for clinical structures. In Chapter 3 we present our international challenge aiming at a large-scale validation of state-of-the-art CAD systems. We also investigate and prove how the combination of different CAD systems reaches performances much higher than any best stand-alone system developed so far. Our results open the possibility to introduce in clinical practice very high-performing CAD systems, which miss a tiny fraction of clinically relevant nodules. Finally, we tested the performance of M5L on clinical data-sets. In chapter 4 we present the results of its clinical validation, which prove the positive impact of CAD as second reader in the diagnosis of pulmonary metastases on oncological patients with extra-thoracic cancers. The proposed approaches have the potential to exploit at best the features of different algorithms, developed independently, for any possible clinical application, setting a collaborative environment for algorithm comparison, combination, clinical validation and, if all of the above were successful, clinical practice

Classification performance for covid patient prognosis from automatic ai segmentation—a single-center study

Background: COVID assessment can be performed using the recently developed individual risk score (prediction of severe respiratory failure in hospitalized patients with SARS-COV2 infection, PREDI-CO score) based on High Resolution Computed Tomography. In this study, we evaluated the possibility of automatizing this estimation using semi-supervised AI-based Radiomics, leveraging the possibility of performing non-supervised segmentation of ground-glass areas. Methods: We collected 92 from patients treated in the IRCCS Sant’Orsola-Malpighi Policlinic and public databases; each lung was segmented using a pre-trained AI method; ground-glass opacity was identified using a novel, non-supervised approach; radiomic measurements were collected and used to predict clinically relevant scores, with particular focus on mortality and the PREDI-CO score. We compared the prediction obtained through different machine learning approaches. Results: All the methods obtained a well-balanced accuracy (70%) on the PREDI-CO score but did not obtain satisfying results on other clinical characteristics due to unbalance between the classes. Conclusions: Semi-supervised segmentation, implemented using a combination of non-supervised segmentation and feature extraction, seems to be a viable approach for patient stratification and could be leveraged to train more complex models. This would be useful in a high-demand situation similar to the current pandemic to support gold-standard segmentation for AI training

Pulmonary nodule segmentation in computed tomography with deep learning

Early detection of lung cancer is essential for treating the disease. Lung nodule segmentation systems can be used together with Computer-Aided Detection (CAD) systems, and help doctors diagnose and manage lung cancer. In this work, we create a lung nodule segmentation system based on deep learning. Deep learning is a sub-field of machine learning responsible for state-of-the-art results in several segmentation datasets such as the PASCAL VOC 2012. Our model is a modified 3D U-Net, trained on the LIDC-IDRI dataset, using the intersection over union (IOU) loss function. We show our model works for multiple types of lung nodules. Our model achieves state-of-the-art performance on the LIDC test set, using nodules annotated by at least 3 radiologists and with a consensus truth of 50%.A deteção do cancro do pulmão numa fase inicial é essencial para o tratamento da doença. Sistemas de segmentação de nódulos pulmonares, usados em junção com sistemas de Deteção Assistida por Computador (DAC), podem ajudar médicos a diagnosticar e gerir o cancro do pulmão. Neste trabalho propomos um sistema de segmentação de nódulos pulmonares, recorrendo a técnicas de aprendizagem profunda. Aprendizagem profunda é um sub-campo de aprendizagem automática, responsável por vários resultados estado da arte em datasets de segmentação de imagem, como o PASCAL VOC 2012. O nosso modelo final é uma 3D U-Net modificada, treinada no dataset LIDC-IDRI, usando interseção sobre união como função de custo. Mostramos que o nosso modelo final funciona com vários tipos de nódulos pulmonares. O nosso modelo consegue resultados estado da arte no LIDC test set, usando nódulos anotados pelo menos por 3 radiologistas, com uma verdade consensual de 50%