A Deep Dive into Understanding Tumor Foci Classification using Multiparametric MRI Based on Convolutional Neural Network

Deep learning models have had a great success in disease classifications using large data pools of skin cancer images or lung X-rays. However, data scarcity has been the roadblock of applying deep learning models directly on prostate multiparametric MRI (mpMRI). Although model interpretation has been heavily studied for natural images for the past few years, there has been a lack of interpretation of deep learning models trained on medical images. This work designs a customized workflow for the small and imbalanced data set of prostate mpMRI where features were extracted from a deep learning model and then analyzed by a traditional machine learning classifier. In addition, this work contributes to revealing how deep learning models interpret mpMRI for prostate cancer patients stratification

Graph Convolutional Networks for Predictive Healthcare using Clinical Notes

학위논문 (석사) -- 서울대학교 대학원 : 공과대학 컴퓨터공학부, 2020. 8. 김선.Clinical notes in Electronic Health Record(EHR) system are recorded in free text forms with different styles and abbreviations of personal preference. Thus, it is very difficult to extract clinically meaningful information from EHR clinical notes. There are many computational methods developed for tasks such as medical text normalization, medical entity extraction, and patient-level prediction tasks. Existing methods for the patient-level prediction task focus on capturing the contextual or sequential information from clinical texts, but they are not designed to capture global and non-consecutive information in the clinical texts. Recently, graph convolutional neural networks(GCNs) are successfully used for text-based classification since GCN can extract the global and long-distance information among the whole texts. However, application of GCN for mining clinical notes is yet to be fully explored. In this study, we propose an end-to-end framework for the analysis of clinical notes using graph neural network-based techniques to predict whether a patient is with MRSA (Methicillin-Resistant Staphylococcus Aureus) positive infection or negative infection. For this MRSA infection prediction, it is critical to capture the patient-specific and global non-consecutive information from patient clinical notes. The clinical notes of a patient are processed to construct a patient-level graph, and each patient-level graph is fed into the GCN-based framework for graph-level supervised learning. The proposed framework consists of a graph convolutional network layer, a graph pooling layer, and a readout layer, followed by a fully connected layer. We tested various settings of the GCN-based framework with various combinations of graph convolution operations and graph pooling methods and we evaluated the performance of each variant framework. In experiments with MRSA infection data, all of the variant frameworks with graph structure information outperformed several baseline methods without using graph structure information with a margin of 2.93%∼11.81%. We also investigated graphs in the pooling step to conduct interpretable analysis in population-based statistical and patient-specific aspects, respectively. With this inspection, we found long-distance word pairs that are distinct for MRSA positive patients and we also showed the pooled graph of the patient that contributes to the patient-specific prediction. Moreover, the Adaboost algorithm was used to improve the performance further. As a result, the framework proposed in this paper reached the highest performance of 85.70%, which is higher than the baseline methods with a margin of 3.71%∼12.59%.전자 건강 기록은 디지털 형태로 체계적으로 수집된 환자의 건강 정보다. 전자 건강 기록이 환자의 상태를 표현 하는 단어들로 구성된 문서의 집합이기때문에 자연어 처리 분야에 적용되는 다양한 기계학습적 방법들이 적용되어왔다. 특히, 딥러닝 기술의 발전으로 인해, 이미지나 텍스트 분야에서 활용 되던 딥러닝 기술 들이생명정보및의학정보분야에점차적용되고있다.하지만,기존의이미지나 텍스트데이터와는 다르게, 전자 건강 기록 데이터는 작성자 및 환자 개개인의 상태에 따라서, 데이터의 환자 특이성이 높다. 또한, 유사한 의미를 지니는 건강 기록들간의 상관관계를 고려해야 할 필요가있다. 본연구에서는 전자 건강 기록 데이터의 환자특이성을 고려한 그래프 기반 딥러닝 모델을 고안하였다. 환자의 전자 건강 기록 데이터와 의료 문서들의 공통 출현 빈도를 활용 하여 환자 특이적 그래프를 생성하였다. 이를 기반으로, 그래프 컨볼루션 네트워크를 사용하여 환자의 병리학적상태를예측하는모델을고안하였다. 연구에서 사용한 데이터는 Methicillin-Resistant Staphylococcus Aureus(MRSA) 감염 여부를 측정한 데이터이다. 고안한 그래프기반 딥러닝 모델을 통해 환자의 내성을 예측한 결과, 그래프정보를 활용 하지 않은 기존모델들 보다 2.93%∼11.81% 뛰어난성능을보였다. 또한 해석 가능한 분석을 수행하기 위해 풀링 단계에서 그래프를 조사했다.이를 통해 MRSA 양성 환자에 대해 구별되는 장거리 단어패턴을 찾았으며 환자별 예측에 기여하는 환자의 합동 그래프를 보여 주었다. 성능을 더욱 향상시키기 위해 아다부스트 알고리즘을 사용하였다. 본 논문에서 제안된 결과는 85.70%로 가장 높은 성능을 기록했으며, 이는 기존 모델보다 3.71%∼12.59%의 향상 시켰음을 보여주었다.Chapter 1 Introduction 1 1.1 Background 1 1.1.1 EHR Clinical Text Data 1 1.1.2 Current methods and limitations 3 1.2 Problem Statement and Contributions 4 Chapter 2 Related Works 6 2.1 Traditional Methods 6 2.2 Deep Learning Methods 7 2.3 Graph Neural Networks 8 2.3.1 Graph Convolutional Networks 8 2.3.2 Graph Pooling Methods 9 2.3.3 Applications of GNN 10 Chapter 3 Methods and Materials 12 3.1 Notation and Problem Definition 12 3.2 Patient Graph Construction Process 14 3.2.1 Parsing and Filtering 15 3.2.2 Word Co-occurrence Finding 16 3.2.3 Patient-level Graph Representation 16 3.3 Word Embedding 17 3.4 Model Architecture 18 3.4.1 Graph Convolutional Network layer 19 3.4.2 Graph Pooling layer 22 3.4.3 Readout Layer 24 3.5 Prediction and Loss Function 25 3.6 Adaboost algorithm 25 Chapter 4 Experiments 27 4.1 EHR Dataset 27 4.1.1 Introduction to MIMIC-III Dataset 27 4.1.2 MRSA Data Collection 28 4.2 Hyper Parameter Settings 28 4.2.1 Model Training 29 4.3 Baseline Models 30 Chapter 5 Results 32 5.1 Performance Comparisons with baseline models 32 5.2 Performance Comparisons with graph networks 33 5.3 Interpretable analysis 34 5.4 Adaboost Result 38 Chapter 6 Conclusion 40 국문초록 49 감사의 글 50Maste

Explainable deep learning classifiers for disease detection based on structural brain MRI data

In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those

Supervised and unsupervised language modelling in Chest X-Ray radiological reports

Chest radiography (CXR) is the most commonly used imaging modality and deep neural network (DNN) algorithms have shown promise in effective triage of normal and abnormal radiograms. Typically, DNNs require large quantities of expertly labelled training exemplars, which in clinical contexts is a major bottleneck to effective modelling, as both considerable clinical skill and time is required to produce high-quality ground truths. In this work we evaluate thirteen supervised classifiers using two large free-text corpora and demonstrate that bi-directional long short-term memory (BiLSTM) networks with attention mechanism effectively identify Normal, Abnormal, and Unclear CXR reports in internal (n = 965 manually-labelled reports, f1-score = 0.94) and external (n = 465 manually-labelled reports, f1-score = 0.90) testing sets using a relatively small number of expert-labelled training observations (n = 3,856 annotated reports). Furthermore, we introduce a general unsupervised approach that accurately distinguishes Normal and Abnormal CXR reports in a large unlabelled corpus. We anticipate that the results presented in this work can be used to automatically extract standardized clinical information from free-text CXR radiological reports, facilitating the training of clinical decision support systems for CXR triage

3D Medical Image Segmentation based on multi-scale MPU-Net

The high cure rate of cancer is inextricably linked to physicians' accuracy in diagnosis and treatment, therefore a model that can accomplish high-precision tumor segmentation has become a necessity in many applications of the medical industry. It can effectively lower the rate of misdiagnosis while considerably lessening the burden on clinicians. However, fully automated target organ segmentation is problematic due to the irregular stereo structure of 3D volume organs. As a basic model for this class of real applications, U-Net excels. It can learn certain global and local features, but still lacks the capacity to grasp spatial long-range relationships and contextual information at multiple scales. This paper proposes a tumor segmentation model MPU-Net for patient volume CT images, which is inspired by Transformer with a global attention mechanism. By combining image serialization with the Position Attention Module, the model attempts to comprehend deeper contextual dependencies and accomplish precise positioning. Each layer of the decoder is also equipped with a multi-scale module and a cross-attention mechanism. The capability of feature extraction and integration at different levels has been enhanced, and the hybrid loss function developed in this study can better exploit high-resolution characteristic information. Moreover, the suggested architecture is tested and evaluated on the Liver Tumor Segmentation Challenge 2017 (LiTS 2017) dataset. Compared with the benchmark model U-Net, MPU-Net shows excellent segmentation results. The dice, accuracy, precision, specificity, IOU, and MCC metrics for the best model segmentation results are 92.17%, 99.08%, 91.91%, 99.52%, 85.91%, and 91.74%, respectively. Outstanding indicators in various aspects illustrate the exceptional performance of this framework in automatic medical image segmentation.Comment: 37 page

Semantic Segmentation of Ambiguous Images

Medizinische Bilder können schwer zu interpretieren sein. Nicht nur weil das Erkennen von Strukturen und möglichen Veränderungen Erfahrung und jahrelanges Training bedarf, sondern auch weil die dargestellten Messungen oft im Kern mehrdeutig sind. Fundamental ist dies eine Konsequenz dessen, dass medizinische Bild-Modalitäten, wie bespielsweise MRT oder CT, nur indirekte Messungen der zu Grunde liegenden molekularen Identitäten bereithalten. Die semantische Bedeutung eines Bildes kann deshalb im Allgemeinen nur gegeben einem größeren Bild-Kontext erfasst werden, welcher es oft allerdings nur unzureichend erlaubt eine eindeutige Interpretation in Form einer einzelnen Hypothese vorzunehmen. Ähnliche Szenarien existieren in natürlichen Bildern, in welchen die Kontextinformation, die es braucht um Mehrdeutigkeiten aufzulösen, limitiert sein kann, beispielsweise aufgrund von Verdeckungen oder Rauschen in der Aufnahme. Zusätzlich können überlappende oder vage Klassen-Definitionen zu schlecht gestellten oder diversen Lösungsräumen führen. Die Präsenz solcher Mehrdeutigkeiten kann auch das Training und die Leistung von maschinellen Lernverfahren beeinträchtigen. Darüber hinaus sind aktuelle Modelle ueberwiegend unfähig komplex strukturierte und diverse Vorhersagen bereitzustellen und stattdessen dazu gezwungen sich auf sub-optimale, einzelne Lösungen oder ununterscheidbare Mixturen zu beschränken. Dies kann besonders problematisch sein wenn Klassifikationsverfahren zu pixel-weisen Vorhersagen wie in der semantischen Segmentierung skaliert werden. Die semantische Segmentierung befasst sich damit jedem Pixel in einem Bild eine Klassen-Kategorie zuzuweisen. Diese Art des detailierten Bild-Verständnisses spielt auch eine wichtige Rolle in der Diagnose und der Behandlung von Krankheiten wie Krebs: Tumore werden häufig in MRT oder CT Bildern entdeckt und deren präzise Lokalisierung und Segmentierung ist von grosser Bedeutung in deren Bewertung, der Vorbereitung möglicher Biopsien oder der Planung von Fokal-Therapien. Diese klinischen Bildverarbeitungen, aber auch die optische Wahrnehmung unserer Umgebung im Rahmen von täglichen Aufgaben wie dem Autofahren, werden momentan von Menschen durchgeführt. Als Teil des zunehmenden Einbindens von maschinellen Lernverfahren in unsere Entscheidungsfindungsprozesse, ist es wichtig diese Aufgaben adequat zu modellieren. Dies schliesst Unsicherheitsabschätzungen der Modellvorhersagen mit ein, mitunter solche Unsicherheiten die den Bild-Mehrdeutigkeiten zugeschrieben werden können. Die vorliegende Thesis schlägt mehrere Art und Weisen vor mit denen mit einer mehrdeutigen Bild-Evidenz umgegangen werden kann. Zunächst untersuchen wir den momentanen klinischen Standard der im Falle von Prostata Läsionen darin besteht, die MRT-sichtbaren Läsionen subjektiv auf ihre Aggressivität hin zu bewerten, was mit einer hohen Variabilität zwischen Bewertern einhergeht. Unseren Studien zufolge können bereits einfache machinelle Lernverfahren und sogar simple quantitative MRT-basierte Parameter besser abschneiden als ein individueller, subjektiver Experte, was ein vielversprechendes Potential der Quantifizerung des Prozesses nahelegt. Desweiteren stellen wir die derzeit erfolgreichste Segmentierungsarchitektur auf einem stark mehrdeutigen Datensatz zur Probe der während klinischer Routine erhoben und annotiert wurde. Unsere Experimente zeigen, dass die standard Segmentierungsverlustfuntion in Szenarien mit starkem Annotationsrauschen sub-optimal sein kann. Als eine Alternative erproben wir die Möglichkeit ein Modell der Verlustunktion zu lernen mit dem Ziel die Koexistenz von plausiblen Lösungen während des Trainings zuzulassen. Wir beobachten gesteigerte Performanz unter Verwendung dieser Trainingsmethode für ansonsten unveränderte neuronale Netzarchitekturen und finden weiter gesteigerte relative Verbesserungen im Limit weniger Daten. Mangel an Daten und Annotationen, hohe Maße an Bild- und Annotationsrauschen sowie mehrdeutige Bild-Evidenz finden sich besonders häufig in Datensätzen medizinischer Bilder wieder. Dieser Teil der Thesis exponiert daher einige der Schwächen die standard Techniken des maschinellen Lernens im Lichte dieser Besonderheiten aufweisen können. Derzeitige Segmentierungsmodelle, wie die zuvor Herangezogenen, sind dahingehend eingeschränkt, dass sie nur eine einzige Vorhersage abgeben können. Dies kontrastiert die Beobachtung dass eine Gruppe von Annotierern, gegeben mehrdeutiger Bilddaten, typischer Weise eine Menge an diverser aber plausibler Annotationen produziert. Um die vorgenannte Modell-Einschränkung zu beheben und die angemessen probabilistische Behandlung der Aufgabe zu ermöglichen, entwickeln wir zwei Modelle, die eine Verteilung über plausible Annotationen vorhersagen statt nur einer einzigen, deterministischen Annotation. Das erste der beiden Modelle kombiniert ein `encoder-decoder\u27 Modell mit dem Verfahren der `variational inference\u27 und verwendet einen globalen `latent vector\u27, der den Raum der möglichen Annotationen für ein gegebenes Bild kodiert. Wir zeigen, dass dieses Modell deutlich besser als die Referenzmethoden abschneidet und gut kalibrierte Unsicherheiten aufweist. Das zweite Modell verbessert diesen Ansatz indem es eine flexiblere und hierarchische Formulierung verwendet, die es erlaubt die Variabilität der Segmentierungen auf verschiedenden Skalen zu erfassen. Dies erhöht die Granularität der Segmentierungsdetails die das Modell produzieren kann und erlaubt es unabhängig variierende Bildregionen und Skalen zu modellieren. Beide dieser neuartigen generativen Segmentierungs-Modelle ermöglichen es, falls angebracht, diverse und kohärente Bild Segmentierungen zu erstellen, was im Kontrast zu früheren Arbeiten steht, welche entweder deterministisch sind, die Modellunsicherheiten auf der Pixelebene modellieren oder darunter leiden eine unangemessen geringe Diversität abzubilden. Im Ergebnis befasst sich die vorliegende Thesis mit der Anwendung von maschinellem Lernen für die Interpretation medizinischer Bilder: Wir zeigen die Möglichkeit auf den klinischen Standard mit Hilfe einer quantitativen Verwendung von Bildparametern, die momentan nur subjektiv in Diagnosen einfliessen, zu verbessern, wir zeigen den möglichen Nutzen eines neuen Trainingsverfahrens um die scheinbare Verletzlichkeit der standard Segmentierungsverlustfunktion gegenüber starkem Annotationsrauschen abzumildern und wir schlagen zwei neue probabilistische Segmentierungsmodelle vor, die die Verteilung über angemessene Annotationen akkurat erlernen können. Diese Beiträge können als Schritte hin zu einer quantitativeren, verstärkt Prinzipien-gestützten und unsicherheitsbewussten Analyse von medizinischen Bildern gesehen werden -ein wichtiges Ziel mit Blick auf die fortschreitende Integration von lernbasierten Systemen in klinischen Arbeitsabläufen

Visualization of dynamic multidimensional and hierarchical datasets

When it comes to tools and techniques designed to help understanding complex abstract data, visualization methods play a prominent role. They enable human operators to lever age their pattern finding, outlier detection, and questioning abilities to visually reason about a given dataset. Many methods exist that create suitable and useful visual represen tations of static abstract, non-spatial, data. However, for temporal abstract, non-spatial, datasets, in which the data changes and evolves through time, far fewer visualization tech niques exist. This thesis focuses on the particular cases of temporal hierarchical data representation via dynamic treemaps, and temporal high-dimensional data visualization via dynamic projec tions. We tackle the joint question of how to extend projections and treemaps to stably, accurately, and scalably handle temporal multivariate and hierarchical data. The literature for static visualization techniques is rich and the state-of-the-art methods have proven to be valuable tools in data analysis. Their temporal/dynamic counterparts, however, are not as well studied, and, until recently, there were few hierarchical and high-dimensional methods that explicitly took into consideration the temporal aspect of the data. In addi tion, there are few or no metrics to assess the quality of these temporal mappings, and even fewer comprehensive benchmarks to compare these methods. This thesis addresses the abovementioned shortcomings. For both dynamic treemaps and dynamic projections, we propose ways to accurately measure temporal stability; we eval uate existing methods considering the tradeoff between stability and visual quality; and we propose new methods that strike a better balance between stability and visual quality than existing state-of-the-art techniques. We demonstrate our methods with a wide range of real-world data, including an application of our new dynamic projection methods to support the analysis and classification of hyperkinetic movement disorder data.Quando se trata de ferramentas e técnicas projetadas para ajudar na compreensão dados abstratos complexos, métodos de visualização desempenham um papel proeminente. Eles permitem que os operadores humanos alavanquem suas habilidades de descoberta de padrões, detecção de valores discrepantes, e questionamento visual para a raciocinar sobre um determinado conjunto de dados. Existem muitos métodos que criam representações visuais adequadas e úteis de para dados estáticos, abstratos, e não-espaciais. No entanto, para dados temporais, abstratos, e não-espaciais, isto é, dados que mudam e evoluem no tempo, existem poucas técnicas apropriadas. Esta tese concentra-se nos casos específicos de representação temporal de dados hierárquicos por meio de treemaps dinâmicos, e visualização temporal de dados de alta dimen sionalidade via projeções dinâmicas. Nós abordar a questão conjunta de como estender projeções e treemaps de forma estável, precisa e escalável para lidar com conjuntos de dados hierárquico-temporais e multivariado-temporais. Em ambos os casos, a literatura para técnicas estáticas é rica e os métodos estado da arte provam ser ferramentas valiosas em análise de dados. Suas contrapartes temporais/dinâmicas, no entanto, não são tão bem estudadas e, até recentemente, existiam poucos métodos hierárquicos e de alta dimensão que explicitamente levavam em consideração o aspecto temporal dos dados. Além disso, existiam poucas métricas para avaliar a qualidade desses mapeamentos visuais temporais, e ainda menos benchmarks abrangentes para comparação esses métodos. Esta tese aborda as deficiências acima mencionadas para treemaps dinâmicos e projeções dinâmicas. Propomos maneiras de medir com precisão a estabilidade temporal; avalia mos os métodos existentes, considerando o compromisso entre estabilidade e qualidade visual; e propomos novos métodos que atingem um melhor equilíbrio entre estabilidade e a qualidade visual do que as técnicas estado da arte atuais. Demonstramos nossos mé todos com uma ampla gama de dados do mundo real, incluindo uma aplicação de nossos novos métodos de projeção dinâmica para apoiar a análise e classificação dos dados de transtorno de movimentos