208 research outputs found

    Predictive analytics applied to Alzheimer’s disease : a data visualisation framework for understanding current research and future challenges

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    Dissertation as a partial requirement for obtaining a master’s degree in information management, with a specialisation in Business Intelligence and Knowledge Management.Big Data is, nowadays, regarded as a tool for improving the healthcare sector in many areas, such as in its economic side, by trying to search for operational efficiency gaps, and in personalised treatment, by selecting the best drug for the patient, for instance. Data science can play a key role in identifying diseases in an early stage, or even when there are no signs of it, track its progress, quickly identify the efficacy of treatments and suggest alternative ones. Therefore, the prevention side of healthcare can be enhanced with the usage of state-of-the-art predictive big data analytics and machine learning methods, integrating the available, complex, heterogeneous, yet sparse, data from multiple sources, towards a better disease and pathology patterns identification. It can be applied for the diagnostic challenging neurodegenerative disorders; the identification of the patterns that trigger those disorders can make possible to identify more risk factors, biomarkers, in every human being. With that, we can improve the effectiveness of the medical interventions, helping people to stay healthy and active for a longer period. In this work, a review of the state of science about predictive big data analytics is done, concerning its application to Alzheimer’s Disease early diagnosis. It is done by searching and summarising the scientific articles published in respectable online sources, putting together all the information that is spread out in the world wide web, with the goal of enhancing knowledge management and collaboration practices about the topic. Furthermore, an interactive data visualisation tool to better manage and identify the scientific articles is develop, delivering, in this way, a holistic visual overview of the developments done in the important field of Alzheimer’s Disease diagnosis.Big Data é hoje considerada uma ferramenta para melhorar o sector da saúde em muitas áreas, tais como na sua vertente mais económica, tentando encontrar lacunas de eficiência operacional, e no tratamento personalizado, selecionando o melhor medicamento para o paciente, por exemplo. A ciência de dados pode desempenhar um papel fundamental na identificação de doenças em um estágio inicial, ou mesmo quando não há sinais dela, acompanhar o seu progresso, identificar rapidamente a eficácia dos tratamentos indicados ao paciente e sugerir alternativas. Portanto, o lado preventivo dos cuidados de saúde pode ser bastante melhorado com o uso de métodos avançados de análise preditiva com big data e de machine learning, integrando os dados disponíveis, geralmente complexos, heterogéneos e esparsos provenientes de múltiplas fontes, para uma melhor identificação de padrões patológicos e da doença. Estes métodos podem ser aplicados nas doenças neurodegenerativas que ainda são um grande desafio no seu diagnóstico; a identificação dos padrões que desencadeiam esses distúrbios pode possibilitar a identificação de mais fatores de risco, biomarcadores, em todo e qualquer ser humano. Com isso, podemos melhorar a eficácia das intervenções médicas, ajudando as pessoas a permanecerem saudáveis e ativas por um período mais longo. Neste trabalho, é feita uma revisão do estado da arte sobre a análise preditiva com big data, no que diz respeito à sua aplicação ao diagnóstico precoce da Doença de Alzheimer. Isto foi realizado através da pesquisa exaustiva e resumo de um grande número de artigos científicos publicados em fontes online de referência na área, reunindo a informação que está amplamente espalhada na world wide web, com o objetivo de aprimorar a gestão do conhecimento e as práticas de colaboração sobre o tema. Além disso, uma ferramenta interativa de visualização de dados para melhor gerir e identificar os artigos científicos foi desenvolvida, fornecendo, desta forma, uma visão holística dos avanços científico feitos no importante campo do diagnóstico da Doença de Alzheimer

    DEEP-AD: The deep learning model for diagnostic classification and prognostic prediction of alzheimer's disease

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    In terms of context, the aim of this dissertation is to aid neuroradiologists in their clinical judgment regarding the early detection of AD by using DL. To that aim, the system design research methodology is suggested in this dissertation for achieving three goals. The first goal is to investigate the DL models that have performed well at identifying patterns associated with AD, as well as the accuracy so far attained, limitations, and gaps. A systematic review of the literature (SLR) revealed a shortage of empirical studies on the early identification of AD through DL. In this regard, thirteen empirical studies were identified and examined. We concluded that three-dimensional (3D) DL models have been generated far less often and that their performance is also inadequate to qualify them for clinical trials. The second goal is to provide the neuroradiologist with the computer-interpretable information they need to analyze neuroimaging biomarkers. Given this context, the next step in this dissertation is to find the optimum DL model to analyze neuroimaging biomarkers. It has been achieved in two steps. In the first step, eight state-of-the-art DL models have been implemented by training from scratch using end-to-end learning (E2EL) for two binary classification tasks (AD vs. CN and AD vs. stable MCI) and compared by utilizing MRI scans from the publicly accessible datasets of neuroimaging biomarkers. Comparative analysis is carried out by utilizing efficiency-effects graphs, comprehensive indicators, and ranking mechanisms. For the training of the AD vs. sMCI task, the EfficientNet-B0 model gets the highest value for the comprehensive indicator and has the fewest parameters. DenseNet264 performed better than the others in terms of evaluation matrices, but since it has the most parameters, it costs more to train. For the AD vs. CN task by DenseNet264, we achieved 100% accuracy for training and 99.56% accuracy for testing. However, the classification accuracy was still only 82.5% for the AD vs. sMCI task. In the second step, fusion of transfer learning (TL) with E2EL is applied to train the EfficientNet-B0 for the AD vs. sMCI task, which achieved 95.29% accuracy for training and 93.10% accuracy for testing. Additionally, we have also implemented EfficientNet-B0 for the multiclass AD vs. CN vs. sMCI classification task with E2EL to be used in ensemble of models and achieved 85.66% training accuracy and 87.38% testing accuracy. To evaluate the model’s robustness, neuroradiologists must validate the implemented model. As a result, the third goal of this dissertation is to create a tool that neuroradiologists may use at their convenience. To achieve this objective, this dissertation proposes a web-based application (DEEP-AD) that has been created by making an ensemble of Efficient-Net B0 and DenseNet 264 (based on the contribution of goal 2). The accuracy of a DEEP-AD prototype has undergone repeated evaluation and improvement. First, we validated 41 subjects of Spanish MRI datasets (acquired from HT Medica, Madrid, Spain), achieving an accuracy of 82.90%, which was later verified by neuroradiologists. The results of these evaluation studies showed the accomplishment of such goals and relevant directions for future research in applied DL for the early detection of AD in clinical settings.En términos de contexto, el objetivo de esta tesis es ayudar a los neurorradiólogos en su juicio clínico sobre la detección precoz de la AD mediante el uso de DL. Para ello, en esta tesis se propone la metodología de investigación de diseño de sistemas para lograr tres objetivos. El segundo objetivo es proporcionar al neurorradiólogo la información interpretable por ordenador que necesita para analizar los biomarcadores de neuroimagen. Dado este contexto, el siguiente paso en esta tesis es encontrar el modelo DL óptimo para analizar biomarcadores de neuroimagen. Esto se ha logrado en dos pasos. En el primer paso, se han implementado ocho modelos DL de última generación mediante entrenamiento desde cero utilizando aprendizaje de extremo a extremo (E2EL) para dos tareas de clasificación binarias (AD vs. CN y AD vs. MCI estable) y se han comparado utilizando escaneos MRI de los conjuntos de datos de biomarcadores de neuroimagen de acceso público. El análisis comparativo se lleva a cabo utilizando gráficos de efecto-eficacia, indicadores exhaustivos y mecanismos de clasificación. Para el entrenamiento de la tarea AD vs. sMCI, el modelo EfficientNet-B0 obtiene el valor más alto para el indicador exhaustivo y tiene el menor número de parámetros. DenseNet264 obtuvo mejores resultados que los demás en términos de matrices de evaluación, pero al ser el que tiene más parámetros, su entrenamiento es más costoso. Para la tarea AD vs. CN de DenseNet264, conseguimos una accuracy del 100% en el entrenamiento y del 99,56% en las pruebas. Sin embargo, la accuracy de la clasificación fue sólo del 82,5% para la tarea AD vs. sMCI. En el segundo paso, se aplica la fusión del aprendizaje por transferencia (TL) con E2EL para entrenar la EfficientNet-B0 para la tarea AD vs. sMCI, que alcanzó una accuracy del 95,29% en el entrenamiento y del 93,10% en las pruebas. Además, también hemos implementado EfficientNet-B0 para la tarea de clasificación multiclase AD vs. CN vs. sMCI con E2EL para su uso en conjuntos de modelos y hemos obtenido una accuracy de entrenamiento del 85,66% y una precisión de prueba del 87,38%. Para evaluar la solidez del modelo, los neurorradiólogos deben validar el modelo implementado. Como resultado, el tercer objetivo de esta disertación es crear una herramienta que los neurorradiólogos puedan utilizar a su conveniencia. Para lograr este objetivo, esta disertación propone una aplicación basada en web (DEEP-AD) que ha sido creada haciendo un ensemble de Efficient-Net B0 y DenseNet 264 (basado en la contribución del objetivo 2). La accuracy del prototipo DEEP-AD ha sido sometida a repetidas evaluaciones y mejoras. En primer lugar, validamos 41 sujetos de conjuntos de datos de MRI españoles (adquiridos de HT Medica, Madrid, España), logrando una accuracy del 82,90%, que posteriormente fue verificada por neurorradiólogos. Los resultados de estos estudios de evaluación mostraron el cumplimiento de dichos objetivos y las direcciones relevantes para futuras investigaciones en DL, aplicada en la detección precoz de la AD en entornos clínicos.Escuela de DoctoradoDoctorado en Tecnologías de la Información y las Telecomunicacione

    Multi-Modal Magnetic Resonance Imaging Predicts Regional Amyloid Burden in the Brain

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    Alzheimer’s disease (AD) is the most common cause of dementia and identifying early markers of this disease is important for prevention and treatment strategies. Amyloid- β (Aβ) protein deposition is one of the earliest detectable pathological changes in AD. But in-vivo detection of Aβ using positron emission tomography (PET) is hampered by high cost and limited geographical accessibility. These factors can become limiting when PET is used to screen large numbers of subjects into prevention trials when only a minority are expected to be amyloid-positive. Structural MRI is advantageous; as it is non-invasive, relatively inexpensive and more accessible. Thus it could be widely used in large studies, even when frequent or repetitive imaging is necessary. We used a machine learning, pattern recognition, approach using intensity-based features from individual and combination of MR modalities (T1 weighted, T2 weighted, T2 fluid attenuated inversion recovery [FLAIR], susceptibility weighted imaging) to predict voxel-level amyloid in the brain. The MR- Aβ relation was learned within each subject and generalized across subjects using subject–specific features (demographic, clinical, and summary MR features). When compared to other modalities, combination of T1-weighted, T2-weighted FLAIR, and SWI performed best in predicting the amyloid status as positive or negative. A combination of T2-weighted and SWI imaging performed the best in predicting change in amyloid over two timepoints. Overall, our results show feasibility of amyloid prediction by MRI and its potential use as an amyloid-screening tool

    Deep learning of brain asymmetry digital biomarkers to support early diagnosis of cognitive decline and dementia

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    Early identification of degenerative processes in the human brain is essential for proper care and treatment. This may involve different instrumental diagnostic methods, including the most popular computer tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. These technologies provide detailed information about the shape, size, and function of the human brain. Structural and functional cerebral changes can be detected by computational algorithms and used to diagnose dementia and its stages (amnestic early mild cognitive impairment - EMCI, Alzheimer’s Disease - AD). They can help monitor the progress of the disease. Transformation shifts in the degree of asymmetry between the left and right hemispheres illustrate the initialization or development of a pathological process in the brain. In this vein, this study proposes a new digital biomarker for the diagnosis of early dementia based on the detection of image asymmetries and crosssectional comparison of NC (normal cognitively), EMCI and AD subjects. Features of brain asymmetries extracted from MRI of the ADNI and OASIS databases are used to analyze structural brain changes and machine learning classification of the pathology. The experimental part of the study includes results of supervised machine learning algorithms and transfer learning architectures of convolutional neural networks for distinguishing between cognitively normal subjects and patients with early or progressive dementia. The proposed pipeline offers a low-cost imaging biomarker for the classification of dementia. It can be potentially helpful to other brain degenerative disorders accompanied by changes in brain asymmetries

    A COMPUTATIONAL PIPELINE FOR MCI DETECTION FROM HETEROGENEOUS BRAIN IMAGES

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    The aging population has increased the importance of identifying and understanding mild cognitive impairment (MCI), particularly given that 6 - 15 % of MCI cases convert to Alzheimer\u27s disease (AD) each year. The early identification of MCI has the potential for timely therapeutic interventions that would limit the advancement of MCI to AD. However, it is difficult to identify MCI-related pathology based on visual inspection because these changes in brain morphology are subtle and spatially distributed. Therefore, reliable and automated methods to identify subtle changes in morphological characteristics of MCI would aid in the identification and understanding of MCI. Meanwhile, usability becomes a major limitation in the development of clinically applicable classifiers. Furthermore, subject privacy is an additional issue in the usage of human brain images. To address the critical need, a complete computer aided diagnosis (CAD) system for automated detection of MCI from heterogeneous brain images is developed. This system provides functions for image processing, classification of MCI subjects from control, visualization of affected regions of interest (ROIs), data sharing among different research sites, and knowledge sharing through image annotation

    MRI-based screening of preclinical Alzheimer's disease for prevention clinical trials

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    The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-180299”.The identification of healthy individuals harboring amyloid pathology represents one important challenge for secondary prevention clinical trials in Alzheimer’s disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% of unnecessary CSF/PET tests and to reduce 47% of the cost of recruitment. This recruitment strategy capitalizes on available MR scans to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD.Peer ReviewedPostprint (author's final draft

    A Knowledge-based Integrative Modeling Approach for <em>In-Silico</em> Identification of Mechanistic Targets in Neurodegeneration with Focus on Alzheimer’s Disease

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    Dementia is the progressive decline in cognitive function due to damage or disease in the body beyond what might be expected from normal aging. Based on neuropathological and clinical criteria, dementia includes a spectrum of diseases, namely Alzheimer's dementia, Parkinson's dementia, Lewy Body disease, Alzheimer's dementia with Parkinson's, Pick's disease, Semantic dementia, and large and small vessel disease. It is thought that these disorders result from a combination of genetic and environmental risk factors. Despite accumulating knowledge that has been gained about pathophysiological and clinical characteristics of the disease, no coherent and integrative picture of molecular mechanisms underlying neurodegeneration in Alzheimer’s disease is available. Existing drugs only offer symptomatic relief to the patients and lack any efficient disease-modifying effects. The present research proposes a knowledge-based rationale towards integrative modeling of disease mechanism for identifying potential candidate targets and biomarkers in Alzheimer’s disease. Integrative disease modeling is an emerging knowledge-based paradigm in translational research that exploits the power of computational methods to collect, store, integrate, model and interpret accumulated disease information across different biological scales from molecules to phenotypes. It prepares the ground for transitioning from ‘descriptive’ to “mechanistic” representation of disease processes. The proposed approach was used to introduce an integrative framework, which integrates, on one hand, extracted knowledge from the literature using semantically supported text-mining technologies and, on the other hand, primary experimental data such as gene/protein expression or imaging readouts. The aim of such a hybrid integrative modeling approach was not only to provide a consolidated systems view on the disease mechanism as a whole but also to increase specificity and sensitivity of the mechanistic model by providing disease-specific context. This approach was successfully used for correlating clinical manifestations of the disease to their corresponding molecular events and led to the identification and modeling of three important mechanistic components underlying Alzheimer’s dementia, namely the CNS, the immune system and the endocrine components. These models were validated using a novel in-silico validation method, namely biomarker-guided pathway analysis and a pathway-based target identification approach was introduced, which resulted in the identification of the MAPK signaling pathway as a potential candidate target at the crossroad of the triad components underlying disease mechanism in Alzheimer’s dementia

    Predicting Alzheimer's disease by segmenting and classifying 3D-brain MRI images using clustering technique and SVM classifiers.

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    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In this thesis, we want to diagnose the Alzheimer’s disease from MRI images. We segment brain MRI images to extract the brain chambers. Then, features are extracted from the segmented area. Finally, a classifier is trained to differentiate between normal and AD brain tissues. We discuss an automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs 2-dimensional (volume slices) and volumetric segmentation methods in order to segment gray matter, white matter and cerebrospinal fluid (CSF), generates a feature vector that characterizes this region, creates a database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database1. We assessed the performance of the classifiers by using results from the clinical tests.Master of Science (M.Sc.) in Computational Science
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