Automated analysis of colorectal cancer

Colorectal cancer (CRC) is the second largest cause of cancer deaths in the UK, with approximately 16,000 per year. Over 41,000 people are diagnosed annually, and 43% of those will die within ten years of diagnosis. The treatment of CRC patients relies on pathological examination of the disease to identify visual features that predict growth and spread, and response to chemoradiotherapy. These prognostic features are identified manually, and are subject to inter and intra-scorer variability. This variability stems from the subjectivity in interpreting large images which can have very varied appearances, as well as the time consuming and laborious methodology of visually inspecting cancer cells. The work in this thesis presents a systematic approach to developing a solution to address this problem for one such prognostic indicator, the Tumour:Stroma Ratio (TSR). The steps taken are presented sequentially through the chapters, in order of the work carried out. These specifically involve the acquisition and assessment of a dataset of 2.4 million expert-classified images of CRC, and multiple iterations of algorithm development, to automate the process of generating TSRs for patient cases. The algorithm improvements are made using conclusions from observer studies, conducted on a psychophysics experiment platform developed as part of this work, and further work is undertaken to identify issues of image quality that affect automated solutions. The developed algorithm is then applied to a clinical trial dataset with survival data, meaning that the algorithm is validated against two separate pathologist-scored, clinical trial datasets, as well as being able to test its suitability for generating independent prognostic markers

Deep Learning-based Computer-Aided Diagnosis systems: a contribution to prostate cancer detection in histopathological images

In this work, novel computer-aided diagnosis systems for medical image analysis focusing on prostate cancer are proposed and implemented. First, the histopathology of prostate cancer was studied, along with the Gleason Grading System, which measures the aggressiveness of a tumor through different patterns with the purpose of driving therapies dealing with this disease. Furthermore, a study of Deep Learning techniques, particularly focusing on neural networks applied to medical image analysis, was conducted. Based on these studies, a Deep Learning-based system to detect malignant regions in gigapixel-size whole-slide prostate cancer tissue images was proposed and developed, which is able to report spatial information of the malignant areas. This solution was evaluated in terms of performance and execution time, obtaining promising results when compared to other state-of-the-art methods. Since the implemented system locates malignant regions within the image without providing a global class, a customWide & Deep network was developed to report a slide-level label per image. The proposed system provides a fast screening method for analyzing histopathological images. Next, a neural network was proposed to assign a specific Gleason pattern to the malignant areas of the tissue. Finally, with the purpose of developing a global computeraided diagnosis system for prostate cancer detection and classification, the three aforementioned subsystems were combined, allowing a complete analysis of histopathological images by reporting whether the sample is normal or malignant, and, in the last case, a heatmap of the malignant areas with their corresponding Gleason pattern. The studied algorithms were also used for other medical image analysis tasks. The performance of these systems were evaluated, discussing the obtained results, presenting conclusions and proposing improvements for future works

Prediction of Chemotherapy Response of Liver Metastases from Baseline CT-Images Using Deep Neural Networks

Dans les pays développés, le cancer colorectal est reconnu comme étant la deuxième cause la plus importante de mortalité liée au cancer. La chimiothérapie est considérée comme un traitement standard pour les métastases colorectales du foie (MCF). Parmi les patients qui développent des MCF, l’évaluation de la réponse du patient au traitement de chimiothérapie est souvent requise pour déterminer le besoin d’une chimiothérapie de seconde ligne, ainsi qu’une éligibilité à la chirurgie. Toutefois, tandis que les régimes basés sur un régime dénommé FOLFOX sont typiquement utilisés pour le traitement de la MCF, l’identification de la sensibilité du patient reste difficile. Les systèmes de diagnostic assistés par ordinateur peuvent fournir de l’information supplémentaire sur la classification des métastases du foie identifiées au niveau des images de diagnostic. Du aux quelques difficultés que rencontrent les radiologues pour distinguer, à l’oeil nu, les lésions traitées des lésions non-traitées, nous proposons dans cette étude un système automatisé basé sur les réseaux profonds convolutifs (RPC). Dans un premier lieu, ces réseaux profonds différencient les lésions traitées des lésions non-traitées, pour ensuite identifier les nouvelles lésions apparaissant sur les tomodensitométries. Ensuite, un réseau de neurones dense émet une prédiction, à partir des lésions non traitées visibles sur les tomodensitométries de prétraitement pour les patients à MCF sous chimiothérapie, sur leur réponse au régime spécifique de chimiothérapie. Dans ce contexte, la référence pour l’évaluation de la réponse au traitement pour le régime approprié de chimiothérapie était le degré de régression de la tumeur en histopathologie. La méthode adoptée dans cette étude nous a aidé à adresser les trois grands objectifs de ce projet de recherche. La première étape était de développer un système automatique de classification des tumeurs traitées et non-traitées à partir des tomodensitométries de patients. La deuxième étape a été de concevoir une nouvelle approche pour prédire la réponse au traitement FOLFOX qui utilise le médicament Bevacizumab en tant que traitement de première ligne. La troisième étape était de prédire le pourcentage de changement volumétrique de la tumeur suivant deux moments temporels consécutifs. Les algorithmes d’intelligence artificielle (IA), et les approches d’apprentissage profond en particulier, ont montré des progrès prometteurs en vision par ordinateur ainsi qu’en traitement d’images. Il existe de nombreuses applications en analyse d’images médicales qui utilisent des réseaux profonds convolutifs pour propulser ces progrès en avant le plus rapidement possible. En pratique, les radiologues et lesmédecins évaluent les images médicales visuellement pour le diagnostic, la détection, la récurrence, le suivi et la caractérisation des maladies. Les méthodes d’apprentissage profond sont souvent supérieures pour la reconnaissance automatique de structures complexes à partir d’images, et quantifier l’évaluation de propriétés et caractéristiques radiographiques.----------ABSTRACT: In developed countries, colorectal cancer is known as the second cause of cancer-related mortality. Chemotherapy is considered a standard treatment for colorectal liver metastases (CLM). Among patients who develop CLM, the assessment of patient response to chemotherapy is often required to determine the need for second-line chemotherapy, and eligibility for surgery. However, a drug regimen known as FOLFOX are typically used for CLM treatment, the identification of responsive patients remains elusive. Computer-aided diagnosis systems may provide insight into the classification of liver metastases identified on diagnostic images. Due to some difficulties for radiologists to distinguish between treated and untreated lesions from the naked eyes, in this study, we propose a fully automated framework based on deep convolutional neural networks (DCNN) which first differentiates treated and untreated lesions to identify new lesions appearing on CT scans, followed by a fully connected neural network to predict from untreated lesions in pre-treatment computed tomography (CT) for patients with CLMundergoing chemotherapy, their response to the specific chemotherapy regimen. In this respect, the ground truth for assessment of treatment response for proper chemotherapy regimen was histopathology to determine the tumor regression grade (TRG). The adopted method in this study helped us to address the three main research objectives. The first step is to develop an automated framework for the classification of treated and untreated tumors based on the patient’s CT images. The second step is to design a new approach for the prediction of response to FOLFOX regimens with Bevacizumab agents as the first-line of treatment. The third step is to predict the percentage of the tumor volume change following two consecutive exams. Artificial intelligence (AI) algorithms, particularly deep learning approach, have shown very astonishing progress in computer vision and image processing tasks. There are several applications in the medical image analysis area which use DCNN to propel these methods forward as quickly as possible. In practice, radiologists and physicians attempt to assess visually medical images for diagnosis, detection, recurrence, monitoring, and characterization of diseases. Deep learning methods surpass at the recognition of complicated patterns from imaging data automatically and quantify the assessment of radiographic features and characteristics

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces

Preprocessing algorithms for the digital histology of colorectal cancer

Pre-processing techniques were developed for cell identification algorithms. These algorithms which locate and classify cells in digital microscopy images are important in digital pathology. The pre-processing methods included image sampling and colour normalisation for standard Haemotoxilyn and Eosin (H&E) images and co-localisation algorithms for multiplexed images. Data studied in the thesis came from patients with colorectal cancer. Patient histology images came from `The Cancer Genome Atlas' (TCGA), a repository with contributions from many different institutional sites. The multiplexed images were created by TIS, the Toponome Imaging System. Experiments with image sampling were applied to TCGA diagnostic images. The effect of sample size and sampling policy were evaluated. TCGA images were also used in experiments with colour normalisation algorithms. For TIS multiplexed images, probabilistic graphical models were developed as well as clustering applications. NW-BHC, an extension to Bayesian Hierarchical Clustering, was developed and, for TIS antibodies, applied to TCGA expression data. Using image sampling with a sample size of 100 tiles gave accurate prediction results while being seven to nine times faster than processing the entire image. The two most accurate colour normalisation methods were that of Macenko and a `Nave' algorithm. Accuracy varied by TCGA site, indicating that researchers should use several independent data sets when evaluating colour normalisation algorithms. Probabilistic graphical models, applied to multiplexed images, calculated links between pairs of antibodies. The application of clustering to cell nuclei resulted in two main groups, one associated with epithelial cells and the second associated with the stromal environment. For TCGA expression data and for several clustering metrics, NW-BHC improved on the standard EM algorithm

Visual and Camera Sensors

This book includes 13 papers published in Special Issue ("Visual and Camera Sensors") of the journal Sensors. The goal of this Special Issue was to invite high-quality, state-of-the-art research papers dealing with challenging issues in visual and camera sensors

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis