Towards Grading Gleason Score using Generically Trained Deep convolutional Neural Networks

We developed an automatic algorithm with the purpose to assist pathologists to report Gleason score on malignant prostatic adenocarcinoma specimen. In order to detect and classify the cancerous tissue, a deep convolutional neural network that had been pre-trained on a large set of photographic images was used. A specific aim was to support intuitive interaction with the result, to let pathologists adjust and correct the output. Therefore, we have designed an algorithm that makes a spatial classification of the whole slide into the same growth patterns as pathologists do. The 22-layer network was cut at an earlier layer and the output from that layer was used to train both a random forest classifier and a support vector machines classifier. At a specific layer a small patch of the image was used to calculate a feature vector and an image is represented by a number of those vectors. We have classified both the individual patches and the entire images. The classification results were compared for different scales of the images and feature vectors from two different layers from the network. Testing was made on a dataset consisting of 213 images, all containing a single class, benign tissue or Gleason score 3-5. Using 10-fold cross validation the accuracy per patch was 81 %. For whole images, the accuracy was increased to 89 %

Improving Prostate Cancer Detection with Breast Histopathology Images

Deep neural networks have introduced significant advancements in the field of machine learning-based analysis of digital pathology images including prostate tissue images. With the help of transfer learning, classification and segmentation performance of neural network models have been further increased. However, due to the absence of large, extensively annotated, publicly available prostate histopathology datasets, several previous studies employ datasets from well-studied computer vision tasks such as ImageNet dataset. In this work, we propose a transfer learning scheme from breast histopathology images to improve prostate cancer detection performance. We validate our approach on annotated prostate whole slide images by using a publicly available breast histopathology dataset as pre-training. We show that the proposed cross-cancer approach outperforms transfer learning from ImageNet dataset.Comment: 9 pages, 2 figure

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

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field

Learning Deep Neural Networks for Enhanced Prostate Histological Image Analysis

In recent years, deep convolutional neural networks (CNNs) have shown promise for improving prostate cancer diagnosis by enabling quantitative histopathology through digital pathology. However, there are a number of factors that limit the widespread adoption and clinical utility of deep learning for digital pathology. One of these limitations is the requirement for large labelled training datasets which are expensive to construct due to limited availability of the requisite expertise. Additionally, digital pathology applications typically require the digitisation of histological slides at high magnifications. This process can be challenging especially when digitising large histological slides such as prostatectomies. This work studies and addresses these issues in two important applications of digital pathology: prostate nuclei detection and cell type classification. We study the performance of CNNs at different magnifications and demonstrate that it is possible to perform nuclei detection in low magnification prostate histopathology using CNNs with minimal loss in accuracy. We then study the training of prostate nuclei detectors in the small data setting and demonstrate that although it is possible to train nuclei detectors with minimal data, the models will be sensitive to hyperparameter choice and therefore may not generalise well. Instead, we show that pre-training the CNNs with colon histology data makes them more robust to hyperparameter choice. We then study the CNN performance for prostate cell type classification using supervised, transfer and semi-supervised learning in the small data setting. Our results show that transfer learning can be detrimental to performance but semi-supervised learning is able to provide significant improvements to the learning curve, allowing the training of neural networks with modest amounts of labelled data. We then propose a novel semi-supervised learning method called Deeply-supervised Exemplar CNNs and demonstrate their ability to improve the cell type classifier learning curves at a much better rate than previous semi-supervised neural network methods

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis.

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field

Deep Learning-Based Grading of Ductal Carcinoma In Situ in Breast Histopathology Images

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed a deep learning-based DCIS grading system. It was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen's kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the observers (o1, o2 and o3) ($\kappa_{o1,dl}=0.81, \kappa_{o2,dl}=0.53, \kappa_{o3,dl}=0.40$) than the observers amongst each other ($\kappa_{o1,o2}=0.58, \kappa_{o1,o3}=0.50, \kappa_{o2,o3}=0.42$) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers ($\kappa_{o1,dl}=0.77, \kappa_{o2,dl}=0.75, \kappa_{o3,dl}=0.70$) as the observers amongst each other ($\kappa_{o1,o2}=0.77, \kappa_{o1,o3}=0.75, \kappa_{o2,o3}=0.72$). In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. We believe this is the first automated system that could assist pathologists by providing robust and reproducible second opinions on DCIS grade

Applications of Deep Learning in Medical Image Analysis : Grading of Prostate Cancer and Detection of Coronary Artery Disease

A wide range of medical examinations are using analysis of images from different types of equipment. Using artificial intelligence, the assessments could be done automatically. This can have multiple benefits for the healthcare; reduce workload for medical doctors, decrease variations in diagnoses and cut waiting times for the patient as well as improve the performance. The aim of this thesis has been to develop such solutions for two common diseases: prostate cancer and coronary artery disease. The methods used are mainly based on deep learning, where the model teaches itself by training on large datasets.Prostate cancer is one of the most common cancer diagnoses among men. The diagnosis is most commonly determined by visual assessment of prostate biopsies in a light microscope according to the Gleason scale. Deep learning methods to automatically detect and grade the cancer areas are presented in this thesis. The methods have been adapted to improve the generalisation performance on images from different hospitals, images which have inevitable variations in e.g.\ stain appearance. The methods include the usage of digital stain normalisation, training with extensive augmentation or using models such as a domain-adversarial neural network. One Gleason grading algorithm was evaluated on a small cohort with biopsies annotated in detail by two pathologists, to compare the performance with pathologists' inter-observer variability. Another cancer detection algorithm was evaluated on a large active surveillance cohort, containing patients with small areas of low-grade cancer. The results are promising towards a future tool to facilitate grading of prostate cancer.Cardiovascular disease is the leading cause of death world-wide, whereof coronary artery disease is one of the most common diseases. One way to diagnose coronary artery disease is by using myocardial perfusion imaging, where disease in the three main arteries supplying the heart with blood can be detected. Methods based on deep learning to perform the detection automatically are presented in this thesis. Furthermore, an algorithm developed to predict the degree of coronary artery stenosis from myocardial perfusion imaging, by means of quantitative coronary angiography, has also been developed. This assessment is normally done using invasive coronary angiography. Making the prediction automatically from myocardial perfusion imaging could save suffering for patients and free resources within the healthcare system