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

AI and Non AI Assessments for Dementia

Current progress in the artificial intelligence domain has led to the development of various types of AI-powered dementia assessments, which can be employed to identify patients at the early stage of dementia. It can revolutionize the dementia care settings. It is essential that the medical community be aware of various AI assessments and choose them considering their degrees of validity, efficiency, practicality, reliability, and accuracy concerning the early identification of patients with dementia (PwD). On the other hand, AI developers should be informed about various non-AI assessments as well as recently developed AI assessments. Thus, this paper, which can be readable by both clinicians and AI engineers, fills the gap in the literature in explaining the existing solutions for the recognition of dementia to clinicians, as well as the techniques used and the most widespread dementia datasets to AI engineers. It follows a review of papers on AI and non-AI assessments for dementia to provide valuable information about various dementia assessments for both the AI and medical communities. The discussion and conclusion highlight the most prominent research directions and the maturity of existing solutions.Comment: 49 page

Abordagem CNN 2D estendida para o diagnóstico da doença de Alzheimer através de imagens de ressonância magnética estrutural

Orientadores: Leticia Rittner, Roberto de Alencar LotufoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: A doença de Alzheimer (AD - Alzheimer's disease) é um tipo de demência que afeta milhões de pessoas em todo o mundo. Até o momento, não há cura para a doença e seu diagnóstico precoce tem sido uma tarefa desafiadora. As técnicas atuais para o seu diagnóstico têm explorado as informações estruturais da Imagem por Ressonância Magnética (MRI - Magnetic Resonance Imaging) em imagens ponderadas em T1. Entre essas técnicas, a rede neural convolucional (CNN - Convolutional Neural Network) é a mais promissora e tem sido usada com sucesso em imagens médicas para uma variedade de aplicações devido à sua capacidade de extração de características. Antes do grande sucesso do aprendizado profundo e das CNNs, os trabalhos que objetivavam classificar os diferentes estágios de AD exploraram abordagens clássicas de aprendizado de máquina e uma meticulosa extração de características, principalmente para classificar testes binários. Recentemente, alguns autores combinaram técnicas de aprendizagem profunda e pequenos subconjuntos do conjunto de dados públicos da Iniciativa de Neuroimagem da Doença de Alzheimer (ADNI - Alzheimer's Disease Neuroimaging Initiative) para prever um estágio inicial da doença explorando abordagens 3D CNN geralmente combinadas com arquiteturas de auto-codificador convolucional 3D. Outros também exploraram uma abordagem de CNN 3D combinando-a ou não com uma etapa de pré-processamento para a extração de características. No entanto, a maioria desses trabalhos focam apenas na classificação binária, sem resultados para AD, comprometimento cognitivo leve (MCI - Mild Cognitive Impairment) e classificação de sujeitos normais (NC - Normal Control). Nosso principal objetivo foi explorar abordagens de CNN 2D para a tarefa de classificação das 3 classes usando imagens de MRI ponderadas em T1. Como objetivo secundário, preenchemos algumas lacunas encontradas na literatura ao investigar o uso de arquiteturas CNN 2D para o nosso problema, uma vez que a maioria dos trabalhos explorou o aprendizado de máquina clássico ou abordagens CNN 3D. Nossa abordagem CNN 2D estendida explora as informações volumétricas dos dados de ressonância magnética, mantendo baixo custo computacional associado a uma abordagem 2D, quando comparados às abordagens 3D. Além disso, nosso resultado supera as outras estratégias para a classificação das 3 classes e comparando o desempenho de nosso modelo com os métodos tradicionais de aprendizado de máquina e 3D CNN. Também investigamos o papel de diferentes técnicas amplamente utilizadas em aplicações CNN, por exemplo, pré-processamento de dados, aumento de dados, transferência de aprendizado e adaptação de domínio para um conjunto de dados brasileiroAbstract: Alzheimer's disease (AD) is a type of dementia that affects millions of people around the world. To date, there is no cure for Alzheimer's and its early-diagnosis has been a challenging task. The current techniques for Alzheimer's disease diagnosis have explored the structural information of Magnetic Resonance Imaging (MRI) in T1-weighted images. Among these techniques, deep convolutional neural network (CNN) is the most promising one and has been successfully used in medical images for a variety of applications due to its ability to perform features extraction. Before the great success of deep learning and CNNs, the works that aimed to classify the different stages of AD explored classic machine learning approaches and a meticulous feature engineering extraction, mostly to classify binary tasks. Recently, some authors have combined deep learning techniques and small subsets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public dataset, to predict an early-stage of AD exploring 3D CNN approaches usually combined with 3D convolutional autoencoder architectures. Others have also investigated a 3D CNN approach combining it or not with a pre-processing step for the extraction of features. However, the majority of these papers focus on binary classification only, with no results for Alzheimer's disease, Mild Cognitive Impairment (MCI), and Normal Control (NC) classification. Our primary goal was to explore 2D CNN approaches to tackle the 3-class classification using T1-weighted MRI. As a secondary goal, we filled some gaps we found in the literature by investigating the use of 2D CNN architectures to our problem, since most of the works either explored traditional machine learning or 3D CNN approaches. Our extended-2D CNN explores the MRI volumetric data information while maintaining the low computational costs associated with a 2D approach when compared to 3D-CNNs. Besides, our result overcomes the other strategies for the 3-class classification while analyzing the performance of our model with traditional machine-learning and 3D-CNN methods. We also investigated the role of different widely used techniques in CNN applications, for instance, data pre-processing, data augmentation, transfer-learning, and domain-adaptation to a Brazilian datasetMestradoEngenharia de ComputaçãoMestra em Engenharia Elétrica168468/2017-4  CNP

Detection of Alzheimer's disease onset using MRI and PET neuroimaging: Longitudinal data analysis and machine learning

The scientists are dedicated to studying the detection of Alzheimer’s disease onset to find a cure, or at the very least, medication that can slow the progression of the disease. This article explores the effectiveness of longitudinal data analysis, artificial intelligence, and machine learning approaches based on magnetic resonance imaging and positron emission tomography neuroimaging modalities for progression estimation and the detection of Alzheimer’s disease onset. The significance of feature extraction in highly complex neuroimaging data, identification of vulnerable brain regions, and the determination of the threshold values for plaques, tangles, and neurodegeneration of these regions will extensively be evaluated. Developing automated methods to improve the aforementioned research areas would enable specialists to determine the progression of the disease and find the link between the biomarkers and more accurate detection of Alzheimer’s disease onset

Biomedical Data Classification with Improvised Deep Learning Architectures

With the rise of very powerful hardware and evolution of deep learning architectures, healthcare data analysis and its applications have been drastically transformed. These transformations mainly aim to aid a healthcare personnel with diagnosis and prognosis of a disease or abnormality at any given point of healthcare routine workflow. For instance, many of the cancer metastases detection depends on pathological tissue procedures and pathologist reviews. The reports of severity classification vary amongst different pathologist, which then leads to different treatment options for a patient. This labor-intensive work can lead to errors or mistreatments resulting in high cost of healthcare. With the help of machine learning and deep learning modules, some of these traditional diagnosis techniques can be improved and aid a doctor in decision making with an unbiased view. Some of such modules can help reduce the cost, shortage of an expertise, and time in identifying the disease. However, there are many other datapoints that are available with medical images, such as omics data, biomarker calculations, patient demographics and history. All these datapoints can enhance disease classification or prediction of progression with the help of machine learning/deep learning modules. However, it is very difficult to find a comprehensive dataset with all different modalities and features in healthcare setting due to privacy regulations. Hence in this thesis, we explore both medical imaging data with clinical datapoints as well as genomics datasets separately for classification tasks using combinational deep learning architectures. We use deep neural networks with 3D volumetric structural magnetic resonance images of Alzheimer Disease dataset for classification of disease. A separate study is implemented to understand classification based on clinical datapoints achieved by machine learning algorithms. For bioinformatics applications, sequence classification task is a crucial step for many metagenomics applications, however, requires a lot of preprocessing that requires sequence assembly or sequence alignment before making use of raw whole genome sequencing data, hence time consuming especially in bacterial taxonomy classification. There are only a few approaches for sequence classification tasks that mainly involve some convolutions and deep neural network. A novel method is developed using an intrinsic nature of recurrent neural networks for 16s rRNA sequence classification which can be adapted to utilize read sequences directly. For this classification task, the accuracy is improved using optimization techniques with a hybrid neural network

Imaging biomarkers in neurodegeneration: current and future practices

Abstract: There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course “Biomarkers in neurodegenerative diseases”. In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis