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

Protein interface prediction using graph convolutional networks

2017 Fall.Includes bibliographical references.Proteins play a critical role in processes both within and between cells, through their interactions with each other and other molecules. Proteins interact via an interface forming a protein complex, which is difficult, expensive, and time consuming to determine experimentally, giving rise to computational approaches. These computational approaches utilize known electrochemical properties of protein amino acid residues in order to predict if they are a part of an interface or not. Prediction can occur in a partner independent fashion, where amino acid residues are considered independently of their neighbor, or in a partner specific fashion, where pairs of potentially interacting residues are considered together. Ultimately, prediction of protein interfaces can help illuminate cellular biology, improve our understanding of diseases, and aide pharmaceutical research. Interface prediction has historically been performed with a variety of methods, to include docking, template matching, and more recently, machine learning approaches. The field of machine learning has undergone a revolution of sorts with the emergence of convolutional neural networks as the leading method of choice for a wide swath of tasks. Enabled by large quantities of data and the increasing power and availability of computing resources, convolutional neural networks efficiently detect patterns in grid structured data and generate hierarchical representations that prove useful for many types of problems. This success has motivated the work presented in this thesis, which seeks to improve upon state of the art interface prediction methods by incorporating concepts from convolutional neural networks. Proteins are inherently irregular, so they don't easily conform to a grid structure, whereas a graph representation is much more natural. Various convolution operations have been proposed for graph data, each geared towards a particular application. We adapted these convolutions for use in interface prediction, and proposed two new variants. Neural networks were trained on the Docking Benchmark Dataset version 4.0 complexes and tested on the new complexes added in version 5.0. Results were compared against the state of the art method partner specific method, PAIRpred [1]. Results show that multiple variants of graph convolution outperform PAIRpred, with no method emerging as the clear winner. In the future, additional training data may be incorporated from other sources, unsupervised pretraining such as autoencoding may be employed, and a generalization of convolution to simplicial complexes may also be explored. In addition, the various graph convolution approaches may be applied to other applications with graph structured data, such as Quantitative Structure Activity Relationship (QSAR) learning, and knowledge base inference

Fully Unsupervised Image Denoising, Diversity Denoising and Image Segmentation with Limited Annotations

Understanding the processes of cellular development and the interplay of cell shape changes, division and migration requires investigation of developmental processes at the spatial resolution of single cell. Biomedical imaging experiments enable the study of dynamic processes as they occur in living organisms. While biomedical imaging is essential, a key component of exposing unknown biological phenomena is quantitative image analysis. Biomedical images, especially microscopy images, are usually noisy owing to practical limitations such as available photon budget, sample sensitivity, etc. Additionally, microscopy images often contain artefacts due to the optical aberrations in microscopes or due to imperfections in camera sensor and internal electronics. The noisy nature of images as well as the artefacts prohibit accurate downstream analysis such as cell segmentation. Although countless approaches have been proposed for image denoising, artefact removal and segmentation, supervised Deep Learning (DL) based content-aware algorithms are currently the best performing for all these tasks. Supervised DL based methods are plagued by many practical limitations. Supervised denoising and artefact removal algorithms require paired corrupted and high quality images for training. Obtaining such image pairs can be very hard and virtually impossible in most biomedical imaging applications owing to photosensitivity and the dynamic nature of the samples being imaged. Similarly, supervised DL based segmentation methods need copious amounts of annotated data for training, which is often very expensive to obtain. Owing to these restrictions, it is imperative to look beyond supervised methods. The objective of this thesis is to develop novel unsupervised alternatives for image denoising, and artefact removal as well as semisupervised approaches for image segmentation. The first part of this thesis deals with unsupervised image denoising and artefact removal. For unsupervised image denoising task, this thesis first introduces a probabilistic approach for training DL based methods using parametric models of imaging noise. Next, a novel unsupervised diversity denoising framework is presented which addresses the fundamentally non-unique inverse nature of image denoising by generating multiple plausible denoised solutions for any given noisy image. Finally, interesting properties of the diversity denoising methods are presented which make them suitable for unsupervised spatial artefact removal in microscopy and medical imaging applications. In the second part of this thesis, the problem of cell/nucleus segmentation is addressed. The focus is especially on practical scenarios where ground truth annotations for training DL based segmentation methods are scarcely available. Unsupervised denoising is used as an aid to improve segmentation performance in the presence of limited annotations. Several training strategies are presented in this work to leverage the representations learned by unsupervised denoising networks to enable better cell/nucleus segmentation in microscopy data. Apart from DL based segmentation methods, a proof-of-concept is introduced which views cell/nucleus segmentation from the perspective of solving a label fusion problem. This method, through limited human interaction, learns to choose the best possible segmentation for each cell/nucleus using only a pool of diverse (and possibly faulty) segmentation hypotheses as input. In summary, this thesis seeks to introduce new unsupervised denoising and artefact removal methods as well as semi-supervised segmentation methods which can be easily deployed to directly and immediately benefit biomedical practitioners with their research

Image Quality Assessment for Population Cardiac MRI: From Detection to Synthesis

Cardiac magnetic resonance (CMR) images play a growing role in diagnostic imaging of cardiovascular diseases. Left Ventricular (LV) cardiac anatomy and function are widely used for diagnosis and monitoring disease progression in cardiology and to assess the patient's response to cardiac surgery and interventional procedures. For population imaging studies, CMR is arguably the most comprehensive imaging modality for non-invasive and non-ionising imaging of the heart and great vessels and, hence, most suited for population imaging cohorts. Due to insufficient radiographer's experience in planning a scan, natural cardiac muscle contraction, breathing motion, and imperfect triggering, CMR can display incomplete LV coverage, which hampers quantitative LV characterization and diagnostic accuracy. To tackle this limitation and enhance the accuracy and robustness of the automated cardiac volume and functional assessment, this thesis focuses on the development and application of state-of-the-art deep learning (DL) techniques in cardiac imaging. Specifically, we propose new image feature representation types that are learnt with DL models and aimed at highlighting the CMR image quality cross-dataset. These representations are also intended to estimate the CMR image quality for better interpretation and analysis. Moreover, we investigate how quantitative analysis can benefit when these learnt image representations are used in image synthesis. Specifically, a 3D fisher discriminative representation is introduced to identify CMR image quality in the UK Biobank cardiac data. Additionally, a novel adversarial learning (AL) framework is introduced for the cross-dataset CMR image quality assessment and we show that the common representations learnt by AL can be useful and informative for cross-dataset CMR image analysis. Moreover, we utilize the dataset invariance (DI) representations for CMR volumes interpolation by introducing a novel generative adversarial nets (GANs) based image synthesis framework, which enhance the CMR image quality cross-dataset

Image Restoration using Automatic Damaged Regions Detection and Machine Learning-Based Inpainting Technique

In this dissertation we propose two novel image restoration schemes. The first pertains to automatic detection of damaged regions in old photographs and digital images of cracked paintings. In cases when inpainting mask generation cannot be completely automatic, our detection algorithm facilitates precise mask creation, particularly useful for images containing damage that is tedious to annotate or difficult to geometrically define. The main contribution of this dissertation is the development and utilization of a new inpainting technique, region hiding, to repair a single image by training a convolutional neural network on various transformations of that image. Region hiding is also effective in object removal tasks. Lastly, we present a segmentation system for distinguishing glands, stroma, and cells in slide images, in addition to current results, as one component of an ongoing project to aid in colon cancer prognostication

Mitotic cell detection in H&E stained meningioma histopathology slides

Indiana University-Purdue University Indianapolis (IUPUI)Meningioma represent more than one-third of all primary central nervous system (CNS) tumors, and it can be classified into three grades according to WHO (World Health Organization) in terms of clinical aggressiveness and risk of recurrence. A key component of meningioma grades is the mitotic count, which is defined as quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at 10 consecutive high-power fields (HPF) on a glass slide under a microscope, which is an extremely laborious and time-consuming process. The goal of this thesis is to investigate the use of computerized methods to automate the detection of mitotic nuclei with limited labeled data. We built computational methods to detect and quantify the histological features of mitotic cells on a whole slides image which mimic the exact process of pathologist workflow. Since we do not have enough training data from meningioma slide, we learned the mitotic cell features through public available breast cancer datasets, and predicted on meingioma slide for accuracy. We use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Hand crafted features are inspired by the domain knowledge, while the data-driven VGG16 models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. Our work on detection of mitotic cells shows 100% recall , 9% precision and 0.17 F1 score. The detection using VGG16 performs with 71% recall, 73% precision, and 0.77 F1 score. Finally, this research of automated image analysis could drastically increase diagnostic efficiency and reduce inter-observer variability and errors in pathology diagnosis, which would allow fewer pathologists to serve more patients while maintaining diagnostic accuracy and precision. And all these methodologies will increasingly transform practice of pathology, allowing it to mature toward a quantitative science

Machine Learning for Camera-Based Monitoring of Laser Welding Processes

Der zunehmende Einsatz automatisierter Laserschweißprozesse stellt hohe Anforderungen an die Prozessüberwachung. Ziel ist es, eine hohe Fügequalität und eine frühestmögliche Fehlererkennung zu gewährleisten. Durch die Verwendung von Methoden des maschinellen Lernens können kostengünstigere und im Optimalfall bereits vorhandene Sensoren zur Überwachung des gesamten Prozesses eingesetzt werden. In dieser Arbeit werden Methoden aufgezeigt, die mit einer an der Fokussieroptik koaxial zum Laserstrahl integrierten Kamera eine Prozessüberwachung vor, während und nach dem Schweißprozess vornehmen. Zur Veranschaulichung der Methoden wird der Kontaktierungsprozess von Kupferdrähten zur Herstellung von Formspulenwicklungen verwendet. Die vorherige Prozessüberwachung umfasst eine durch ein faltendes neuronales Netz optimierte Bauteillagedetektion. Durch ei ne Formprüfung der detektierten Fügekomponenten können zudem vorverarbeitende Schritte überwacht und die Schweißung fehlerhafter Bauteile vermieden werden. Die prozessbegleitende Überwachung konzentriert sich auf die Erkennung von Spritzern, da diese als Indikator für einen instabilen Prozess dienen. Algorithmen des maschinellen Lernens führen eine semantische Segmentierung durch, die eine klare Unterscheidung zwischen Rauch, Prozesslicht und Materialauswurf ermöglicht. Die Qualitätsbewertung nach dem Prozess beinhaltet die Extraktion von Informationen über Größe und Form der Anbindungsfläche aus dem Kamerabild. Zudem wird ein Verfahren vorgeschlagen, welches anhand eines Kamerabildes mit Methoden des maschinellen Lernens die Höhendaten berechnet. Anhand der Höhenkarte wird eine regelbasierte Qualitätsbewertung der Schweißnähte durchgeführt. Bei allen Algorithmen wird die Integrierbarkeit in industrielle Prozesse berücksichtigt. Hierzu zählen unter anderem eine geringe Datengrundlage, eine begrenzte Inferenzhardware aus der industriellen Fertigung und die Akzeptanz beim Anwender

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Modelling Non-Equilibrium Molecular Formation and Dissociation for the Spectroscopic Analysis of Cool Stellar Atmospheres

Modelling techniques for stellar atmospheres are undergoing continuous improvement. In this thesis, I showcase how these methods are used for spectroscopic analysis and for modelling time-dependent molecular formation and dissociation. I first use CO5BOLD model atmospheres with the LINFOR3D spectrum synthesis code to determine the photospheric solar silicon abundance of 7.57 ± 0.04. This work also revealed some issues present in the cutting-edge methods, such as synthesised lines being overly broadened. Next, I constructed a chemical reaction network in order to model the time-dependent evolution of molecular species in (carbon-enhanced) metal-poor dwarf and red giant atmospheres, again using CO5 BOLD. This was to test if the assumption of chemical equi librium, widely assumed in spectroscopic studies, was still vaild in the photospheres of metal-poor stars. Indeed, the mean deviations from chemical equilibrium are below 0.2 dex across the spectroscopically relevant regions of the atmosphere, though deviations increase with height. Finally, I implemented machine learning methods in order to remove noise and line blends from spectra, as well as to predict the equilibrium state of a chemical reaction network. The methods used and developed in this thesis illustrate the importance of both conventional and machine learning modelling techniques, and merge them to further improve accuracy, precision, and efficiency