Longitudinal Brain Tumor Tracking, Tumor Grading, and Patient Survival Prediction Using MRI

This work aims to develop novel methods for brain tumor classification, longitudinal brain tumor tracking, and patient survival prediction. Consequently, this dissertation proposes three tasks. First, we develop a framework for brain tumor segmentation prediction in longitudinal multimodal magnetic resonance imaging (mMRI) scans, comprising two methods: feature fusion and joint label fusion (JLF). The first method fuses stochastic multi-resolution texture features with tumor cell density features, in order to obtain tumor segmentation predictions in follow-up scans from a baseline pre-operative timepoint. The second method utilizes JLF to combine segmentation labels obtained from (i) the stochastic texture feature-based and Random Forest (RF)-based tumor segmentation method; and (ii) another state-of-the-art tumor growth and segmentation method known as boosted Glioma Image Segmentation and Registration (GLISTRboost, or GB). With the advantages of feature fusion and label fusion, we achieve state-of-the-art brain tumor segmentation prediction. Second, we propose a deep neural network (DNN) learning-based method for brain tumor type and subtype grading using phenotypic and genotypic data, following the World Health Organization (WHO) criteria. In addition, the classification method integrates a cellularity feature which is derived from the morphology of a pathology image to improve classification performance. The proposed method achieves state-of-the-art performance for tumor grading following the new CNS tumor grading criteria. Finally, we investigate brain tumor volume segmentation, tumor subtype classification, and overall patient survival prediction, and then we propose a new context- aware deep learning method, known as the Context Aware Convolutional Neural Network (CANet). Using the proposed method, we participated in the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) for brain tumor volume segmentation and overall survival prediction tasks. In addition, we also participated in the Radiology-Pathology Challenge 2019 (CPM-RadPath 2019) for Brain Tumor Subtype Classification, organized by the Medical Image Computing & Computer Assisted Intervention (MICCAI) Society. The online evaluation results show that the proposed methods offer competitive performance from their use of state-of-the-art methods in tumor volume segmentation, promising performance on overall survival prediction, and state-of-the-art performance on tumor subtype classification. Moreover, our result was ranked second place in the testing phase of the CPM-RadPath 2019

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

Deep Networks Based Energy Models for Object Recognition from Multimodality Images

Object recognition has been extensively investigated in computer vision area, since it is a fundamental and essential technique in many important applications, such as robotics, auto-driving, automated manufacturing, and security surveillance. According to the selection criteria, object recognition mechanisms can be broadly categorized into object proposal and classification, eye fixation prediction and saliency object detection. Object proposal tends to capture all potential objects from natural images, and then classify them into predefined groups for image description and interpretation. For a given natural image, human perception is normally attracted to the most visually important regions/objects. Therefore, eye fixation prediction attempts to localize some interesting points or small regions according to human visual system (HVS). Based on these interesting points and small regions, saliency object detection algorithms propagate the important extracted information to achieve a refined segmentation of the whole salient objects. In addition to natural images, object recognition also plays a critical role in clinical practice. The informative insights of anatomy and function of human body obtained from multimodality biomedical images such as magnetic resonance imaging (MRI), transrectal ultrasound (TRUS), computed tomography (CT) and positron emission tomography (PET) facilitate the precision medicine. Automated object recognition from biomedical images empowers the non-invasive diagnosis and treatments via automated tissue segmentation, tumor detection and cancer staging. The conventional recognition methods normally utilize handcrafted features (such as oriented gradients, curvature, Haar features, Haralick texture features, Laws energy features, etc.) depending on the image modalities and object characteristics. It is challenging to have a general model for object recognition. Superior to handcrafted features, deep neural networks (DNN) can extract self-adaptive features corresponding with specific task, hence can be employed for general object recognition models. These DNN-features are adjusted semantically and cognitively by over tens of millions parameters corresponding to the mechanism of human brain, therefore leads to more accurate and robust results. Motivated by it, in this thesis, we proposed DNN-based energy models to recognize object on multimodality images. For the aim of object recognition, the major contributions of this thesis can be summarized below: 1. We firstly proposed a new comprehensive autoencoder model to recognize the position and shape of prostate from magnetic resonance images. Different from the most autoencoder-based methods, we focused on positive samples to train the model in which the extracted features all come from prostate. After that, an image energy minimization scheme was applied to further improve the recognition accuracy. The proposed model was compared with three classic classifiers (i.e. support vector machine with radial basis function kernel, random forest, and naive Bayes), and demonstrated significant superiority for prostate recognition on magnetic resonance images. We further extended the proposed autoencoder model for saliency object detection on natural images, and the experimental validation proved the accurate and robust saliency object detection results of our model. 2. A general multi-contexts combined deep neural networks (MCDN) model was then proposed for object recognition from natural images and biomedical images. Under one uniform framework, our model was performed in multi-scale manner. Our model was applied for saliency object detection from natural images as well as prostate recognition from magnetic resonance images. Our experimental validation demonstrated that the proposed model was competitive to current state-of-the-art methods. 3. We designed a novel saliency image energy to finely segment salient objects on basis of our MCDN model. The region priors were taken into account in the energy function to avoid trivial errors. Our method outperformed state-of-the-art algorithms on five benchmarking datasets. In the experiments, we also demonstrated that our proposed saliency image energy can boost the results of other conventional saliency detection methods

Deep Multimodality Image-Guided System for Assisting Neurosurgery

Intrakranielle Hirntumoren gehören zu den zehn häufigsten bösartigen Krebsarten und sind für eine erhebliche Morbidität und Mortalität verantwortlich. Die größte histologische Kategorie der primären Hirntumoren sind die Gliome, die ein äußerst heterogenes Erschei-nungsbild aufweisen und radiologisch schwer von anderen Hirnläsionen zu unterscheiden sind. Die Neurochirurgie ist meist die Standardbehandlung für neu diagnostizierte Gliom-Patienten und kann von einer Strahlentherapie und einer adjuvanten Temozolomid-Chemotherapie gefolgt werden. Die Hirntumorchirurgie steht jedoch vor großen Herausforderungen, wenn es darum geht, eine maximale Tumorentfernung zu erreichen und gleichzeitig postoperative neurologische Defizite zu vermeiden. Zwei dieser neurochirurgischen Herausforderungen werden im Folgenden vorgestellt. Erstens ist die manuelle Abgrenzung des Glioms einschließlich seiner Unterregionen aufgrund seines infiltrativen Charakters und des Vorhandenseins einer heterogenen Kontrastverstärkung schwierig. Zweitens verformt das Gehirn seine Form ̶ die so genannte "Hirnverschiebung" ̶ als Reaktion auf chirurgische Manipulationen, Schwellungen durch osmotische Medikamente und Anästhesie, was den Nutzen präopera-tiver Bilddaten für die Steuerung des Eingriffs einschränkt. Bildgesteuerte Systeme bieten Ärzten einen unschätzbaren Einblick in anatomische oder pathologische Ziele auf der Grundlage moderner Bildgebungsmodalitäten wie Magnetreso-nanztomographie (MRT) und Ultraschall (US). Bei den bildgesteuerten Instrumenten handelt es sich hauptsächlich um computergestützte Systeme, die mit Hilfe von Computer-Vision-Methoden die Durchführung perioperativer chirurgischer Eingriffe erleichtern. Die Chirurgen müssen jedoch immer noch den Operationsplan aus präoperativen Bildern gedanklich mit Echtzeitinformationen zusammenführen, während sie die chirurgischen Instrumente im Körper manipulieren und die Zielerreichung überwachen. Daher war die Notwendigkeit einer Bildführung während neurochirurgischer Eingriffe schon immer ein wichtiges Anliegen der Ärzte. Ziel dieser Forschungsarbeit ist die Entwicklung eines neuartigen Systems für die peri-operative bildgeführte Neurochirurgie (IGN), nämlich DeepIGN, mit dem die erwarteten Ergebnisse der Hirntumorchirurgie erzielt werden können, wodurch die Gesamtüberle-bensrate maximiert und die postoperative neurologische Morbidität minimiert wird. Im Rahmen dieser Arbeit werden zunächst neuartige Methoden für die Kernbestandteile des DeepIGN-Systems der Hirntumor-Segmentierung im MRT und der multimodalen präope-rativen MRT zur intraoperativen US-Bildregistrierung (iUS) unter Verwendung der jüngs-ten Entwicklungen im Deep Learning vorgeschlagen. Anschließend wird die Ergebnisvor-hersage der verwendeten Deep-Learning-Netze weiter interpretiert und untersucht, indem für den Menschen verständliche, erklärbare Karten erstellt werden. Schließlich wurden Open-Source-Pakete entwickelt und in weithin anerkannte Software integriert, die für die Integration von Informationen aus Tracking-Systemen, die Bildvisualisierung und -fusion sowie die Anzeige von Echtzeit-Updates der Instrumente in Bezug auf den Patientenbe-reich zuständig ist. Die Komponenten von DeepIGN wurden im Labor validiert und in einem simulierten Operationssaal evaluiert. Für das Segmentierungsmodul erreichte DeepSeg, ein generisches entkoppeltes Deep-Learning-Framework für die automatische Abgrenzung von Gliomen in der MRT des Gehirns, eine Genauigkeit von 0,84 in Bezug auf den Würfelkoeffizienten für das Bruttotumorvolumen. Leistungsverbesserungen wurden bei der Anwendung fort-schrittlicher Deep-Learning-Ansätze wie 3D-Faltungen über alle Schichten, regionenbasier-tes Training, fliegende Datenerweiterungstechniken und Ensemble-Methoden beobachtet. Um Hirnverschiebungen zu kompensieren, wird ein automatisierter, schneller und genauer deformierbarer Ansatz, iRegNet, für die Registrierung präoperativer MRT zu iUS-Volumen als Teil des multimodalen Registrierungsmoduls vorgeschlagen. Es wurden umfangreiche Experimente mit zwei Multi-Location-Datenbanken durchgeführt: BITE und RESECT. Zwei erfahrene Neurochirurgen führten eine zusätzliche qualitative Validierung dieser Studie durch, indem sie MRT-iUS-Paare vor und nach der deformierbaren Registrierung überlagerten. Die experimentellen Ergebnisse zeigen, dass das vorgeschlagene iRegNet schnell ist und die besten Genauigkeiten erreicht. Darüber hinaus kann das vorgeschlagene iRegNet selbst bei nicht trainierten Bildern konkurrenzfähige Ergebnisse liefern, was seine Allgemeingültigkeit unter Beweis stellt und daher für die intraoperative neurochirurgische Führung von Nutzen sein kann. Für das Modul "Erklärbarkeit" wird das NeuroXAI-Framework vorgeschlagen, um das Vertrauen medizinischer Experten in die Anwendung von KI-Techniken und tiefen neuro-nalen Netzen zu erhöhen. Die NeuroXAI umfasst sieben Erklärungsmethoden, die Visuali-sierungskarten bereitstellen, um tiefe Lernmodelle transparent zu machen. Die experimen-tellen Ergebnisse zeigen, dass der vorgeschlagene XAI-Rahmen eine gute Leistung bei der Extraktion lokaler und globaler Kontexte sowie bei der Erstellung erklärbarer Salienzkar-ten erzielt, um die Vorhersage des tiefen Netzwerks zu verstehen. Darüber hinaus werden Visualisierungskarten erstellt, um den Informationsfluss in den internen Schichten des Encoder-Decoder-Netzwerks zu erkennen und den Beitrag der MRI-Modalitäten zur end-gültigen Vorhersage zu verstehen. Der Erklärungsprozess könnte medizinischen Fachleu-ten zusätzliche Informationen über die Ergebnisse der Tumorsegmentierung liefern und somit helfen zu verstehen, wie das Deep-Learning-Modell MRT-Daten erfolgreich verar-beiten kann. Außerdem wurde ein interaktives neurochirurgisches Display für die Eingriffsführung entwickelt, das die verfügbare kommerzielle Hardware wie iUS-Navigationsgeräte und Instrumentenverfolgungssysteme unterstützt. Das klinische Umfeld und die technischen Anforderungen des integrierten multimodalen DeepIGN-Systems wurden mit der Fähigkeit zur Integration von (1) präoperativen MRT-Daten und zugehörigen 3D-Volumenrekonstruktionen, (2) Echtzeit-iUS-Daten und (3) positioneller Instrumentenver-folgung geschaffen. Die Genauigkeit dieses Systems wurde anhand eines benutzerdefi-nierten Agar-Phantom-Modells getestet, und sein Einsatz in einem vorklinischen Operati-onssaal wurde simuliert. Die Ergebnisse der klinischen Simulation bestätigten, dass die Montage des Systems einfach ist, in einer klinisch akzeptablen Zeit von 15 Minuten durchgeführt werden kann und mit einer klinisch akzeptablen Genauigkeit erfolgt. In dieser Arbeit wurde ein multimodales IGN-System entwickelt, das die jüngsten Fort-schritte im Bereich des Deep Learning nutzt, um Neurochirurgen präzise zu führen und prä- und intraoperative Patientenbilddaten sowie interventionelle Geräte in das chirurgi-sche Verfahren einzubeziehen. DeepIGN wurde als Open-Source-Forschungssoftware entwickelt, um die Forschung auf diesem Gebiet zu beschleunigen, die gemeinsame Nut-zung durch mehrere Forschungsgruppen zu erleichtern und eine kontinuierliche Weiter-entwicklung durch die Gemeinschaft zu ermöglichen. Die experimentellen Ergebnisse sind sehr vielversprechend für die Anwendung von Deep-Learning-Modellen zur Unterstützung interventioneller Verfahren - ein entscheidender Schritt zur Verbesserung der chirurgi-schen Behandlung von Hirntumoren und der entsprechenden langfristigen postoperativen Ergebnisse

Multi-Modality Pathology Segmentation Framework: Application to Cardiac Magnetic Resonance Images

Multi-sequence of cardiac magnetic resonance (CMR) images can provide complementary information for myocardial pathology (scar and edema). However, it is still challenging to fuse these underlying information for pathology segmentation effectively. This work presents an automatic cascade pathology segmentation framework based on multi-modality CMR images. It mainly consists of two neural networks: an anatomical structure segmentation network (ASSN) and a pathological region segmentation network (PRSN). Specifically, the ASSN aims to segment the anatomical structure where the pathology may exist, and it can provide a spatial prior for the pathological region segmentation. In addition, we integrate a denoising auto-encoder (DAE) into the ASSN to generate segmentation results with plausible shapes. The PRSN is designed to segment pathological region based on the result of ASSN, in which a fusion block based on channel attention is proposed to better aggregate multi-modality information from multi-modality CMR images. Experiments from the MyoPS2020 challenge dataset show that our framework can achieve promising performance for myocardial scar and edema segmentation.Comment: 12 pages,MyoPS 202

Machine Learning in Medical Image Analysis

Machine learning is playing a pivotal role in medical image analysis. Many algorithms based on machine learning have been applied in medical imaging to solve classification, detection, and segmentation problems. Particularly, with the wide application of deep learning approaches, the performance of medical image analysis has been significantly improved. In this thesis, we investigate machine learning methods for two key challenges in medical image analysis: The first one is segmentation of medical images. The second one is learning with weak supervision in the context of medical imaging. The first main contribution of the thesis is a series of novel approaches for image segmentation. First, we propose a framework based on multi-scale image patches and random forests to segment small vessel disease (SVD) lesions on computed tomography (CT) images. This framework is validated in terms of spatial similarity, estimated lesion volumes, visual score ratings and was compared with human experts. The results showed that the proposed framework performs as well as human experts. Second, we propose a generic convolutional neural network (CNN) architecture called the DRINet for medical image segmentation. The DRINet approach is robust in three different types of segmentation tasks, which are multi-class cerebrospinal fluid (CSF) segmentation on brain CT images, multi-organ segmentation on abdomen CT images, and multi-class tumour segmentation on brain magnetic resonance (MR) images. Finally, we propose a CNN-based framework to segment acute ischemic lesions on diffusion weighted (DW)-MR images, where the lesions are highly variable in terms of position, shape, and size. Promising results were achieved on a large clinical dataset. The second main contribution of the thesis is two novel strategies for learning with weak supervision. First, we propose a novel strategy called context restoration to make use of the images without annotations. The context restoration strategy is a proxy learning process based on the CNN, which extracts semantic features from images without using annotations. It was validated on classification, localization, and segmentation problems and was superior to existing strategies. Second, we propose a patch-based framework using multi-instance learning to distinguish normal and abnormal SVD on CT images, where there are only coarse-grained labels available. Our framework was observed to work better than classic methods and clinical practice.Open Acces

Evidence fusion with contextual discounting for multi-modality medical image segmentation

As information sources are usually imperfect, it is necessary to take into account their reliability in multi-source information fusion tasks. In this paper, we propose a new deep framework allowing us to merge multi-MR image segmentation results using the formalism of Dempster-Shafer theory while taking into account the reliability of different modalities relative to different classes. The framework is composed of an encoder-decoder feature extraction module, an evidential segmentation module that computes a belief function at each voxel for each modality, and a multi-modality evidence fusion module, which assigns a vector of discount rates to each modality evidence and combines the discounted evidence using Dempster's rule. The whole framework is trained by minimizing a new loss function based on a discounted Dice index to increase segmentation accuracy and reliability. The method was evaluated on the BraTs 2021 database of 1251 patients with brain tumors. Quantitative and qualitative results show that our method outperforms the state of the art, and implements an effective new idea for merging multi-information within deep neural networks.Comment: MICCAI202

Offline and Online Interactive Frameworks for MRI and CT Image Analysis in the Healthcare Domain : The Case of COVID-19, Brain Tumors and Pancreatic Tumors

Medical imaging represents the organs, tissues and structures underneath the outer layers of skin and bones etc. and stores information on normal anatomical structures for abnormality detection and diagnosis. In this thesis, tools and techniques are used to automate the analysis of medical images, emphasizing the detection of brain tumor anomalies from brain MRIs, Covid infections from lung CT images and pancreatic tumor from pancreatic CT images. Image processing methods such as filtering and thresholding models, geometry models, graph models, region-based analysis, connected component analysis, machine learning models, and recent deep learning models are used. The following problems for medical images : abnormality detection, abnormal region segmentation, interactive user interface to represent the results of detection and segmentation while receiving feedbacks from healthcare professionals to improve the analysis procedure, and finally report generation, are considered in this research. Complete interactive systems containing conventional models, machine learning, and deep learning methods for different types of medical abnormalities have been proposed and developed in this thesis. The experimental results show promising outcomes that has led to the incorporation of the methods for the proposed solutions based on the observations of the performance metrics and their comparisons. Although currently separate systems have been developed for brain tumor, Covid and pancreatic cancer, the success of the developed systems show a promising potential to combine them to form a generalized system for analyzing medical imaging of different types collected from any organs to detect any type of abnormalities