Role of Artificial Intelligence (AI) art in care of ageing society: focus on dementia

open access articleBackground: Art enhances both physical and mental health wellbeing. The health benefits include reduction in blood pressure, heart rate, pain perception and briefer inpatient stays, as well as improvement of communication skills and self-esteem. In addition to these, people living with dementia benefit from reduction of their noncognitive, behavioural changes, enhancement of their cognitive capacities and being socially active. Methods: The current study represents a narrative general literature review on available studies and knowledge about contribution of Artificial Intelligence (AI) in creative arts. Results: We review AI visual arts technologies, and their potential for use among people with dementia and care, drawing on similar experiences to date from traditional art in dementia care. Conclusion: The virtual reality, installations and the psychedelic properties of the AI created art provide a new venue for more detailed research about its therapeutic use in dementia

A Neuroimaging Web Interface for Data Acquisition, Processing and Visualization of Multimodal Brain Images

Structural and functional brain images are generated as essential modalities for medical experts to learn about the different functions of the brain. These images are typically visually inspected by experts. Many software packages are available to process medical images, but they are complex and difficult to use. The software packages are also hardware intensive. As a consequence, this dissertation proposes a novel Neuroimaging Web Services Interface (NWSI) as a series of processing pipelines for a common platform to store, process, visualize and share data. The NWSI system is made up of password-protected interconnected servers accessible through a web interface. The web-interface driving the NWSI is based on Drupal, a popular open source content management system. Drupal provides a user-based platform, in which the core code for the security and design tools are updated and patched frequently. New features can be added via modules, while maintaining the core software secure and intact. The webserver architecture allows for the visualization of results and the downloading of tabulated data. Several forms are ix available to capture clinical data. The processing pipeline starts with a FreeSurfer (FS) reconstruction of T1-weighted MRI images. Subsequently, PET, DTI, and fMRI images can be uploaded. The Webserver captures uploaded images and performs essential functionalities, while processing occurs in supporting servers. The computational platform is responsive and scalable. The current pipeline for PET processing calculates all regional Standardized Uptake Value ratios (SUVRs). The FS and SUVR calculations have been validated using Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) results posted at Laboratory of Neuro Imaging (LONI). The NWSI system provides access to a calibration process through the centiloid scale, consolidating Florbetapir and Florbetaben tracers in amyloid PET images. The interface also offers onsite access to machine learning algorithms, and introduces new heat maps that augment expert visual rating of PET images. NWSI has been piloted using data and expertise from Mount Sinai Medical Center, the 1Florida Alzheimer’s Disease Research Center (ADRC), Baptist Health South Florida, Nicklaus Children\u27s Hospital, and the University of Miami. All results were obtained using our processing servers in order to maintain data validity, consistency, and minimal processing bias

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

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

A machine learning approach towards detecting dementia based on its modifiable risk factors

Dementia is considered one of the greatest global health and social care challenges in the 21st century. Fortunately, dementia can be delayed or possibly prevented by changes in lifestyle as dictated through known modifiable risk factors. These risk factors include low education, hypertension, obesity, hearing loss, depression, diabetes, physical inactivity, smoking, and social isolation. Other risk factors are non- modifiable and include aging and genetics. The main goal of this study is to demonstrate how machine learning methods can help predict dementia based on an individual’s modifiable risk factors profile. We use publicly available datasets for training algorithms to predict participant’ s cognitive state diagnosis, as cognitive normal or mild cognitive impairment or dementia. Several approaches were implemented using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) longitudinal study. The best classification results were obtained using both the Lancet and the Libra risk factor lists via longitudinal datasets, which outperformed cross-sectional baseline datasets. Moreover, using only data of the most recent visits provided even better results than using the complete longitudinal set. A binary classification (dementia vs non- dementia) yielded approximately 92% accuracy, while the full multi-class prediction performance yielded to a 77% accuracy using logistic regression, followed by random forest with 92% and 70% respectively. The results demonstrate the utility of machine learning in the prediction of cognitive impairment based on modifiable risk factors and may encourage interventions to reduce the prevalence or severity of the condition in large populations

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

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

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

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&#8217;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

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

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

Machine Learning Methods for Structural Brain MRIs: Applications for Alzheimer’s Disease and Autism Spectrum Disorder

This thesis deals with the development of novel machine learning applications to automatically detect brain disorders based on magnetic resonance imaging (MRI) data, with a particular focus on Alzheimer’s disease and the autism spectrum disorder. Machine learning approaches are used extensively in neuroimaging studies of brain disorders to investigate abnormalities in various brain regions. However, there are many technical challenges in the analysis of neuroimaging data, for example, high dimensionality, the limited amount of data, and high variance in that data due to many confounding factors. These limitations make the development of appropriate computational approaches more challenging. To deal with these existing challenges, we target multiple machine learning approaches, including supervised and semi-supervised learning, domain adaptation, and dimensionality reduction methods.In the current study, we aim to construct effective biomarkers with sufficient sensitivity and specificity that can help physicians better understand the diseases and make improved diagnoses or treatment choices. The main contributions are 1) development of a novel biomarker for predicting Alzheimer’s disease in mild cognitive impairment patients by integrating structural MRI data and neuropsychological test results and 2) the development of a new computational approach for predicting disease severity in autistic patients in agglomerative data by automatically combining structural information obtained from different brain regions.In addition, we investigate various data-driven feature selection and classification methods for whole brain, voxel-based classification analysis of structural MRI and the use of semi-supervised learning approaches to predict Alzheimer’s disease. We also analyze the relationship between disease-related structural changes and cognitive states of patients with Alzheimer’s disease.The positive results of this effort provide insights into how to construct better biomarkers based on multisource data analysis of patient and healthy cohorts that may enable early diagnosis of brain disorders, detection of brain abnormalities and understanding effective processing in patient and healthy groups. Further, the methodologies and basic principles presented in this thesis are not only suited to the studied cases, but also are applicable to other similar problems

Dealing with heterogeneity in the prediction of clinical diagnosis

Le diagnostic assisté par ordinateur est un domaine de recherche en émergence et se situe à l’intersection de l’imagerie médicale et de l’apprentissage machine. Les données médi- cales sont de nature très hétérogène et nécessitent une attention particulière lorsque l’on veut entraîner des modèles de prédiction. Dans cette thèse, j’ai exploré deux sources d’hétérogénéité, soit l’agrégation multisites et l’hétérogénéité des étiquettes cliniques dans le contexte de l’imagerie par résonance magnétique (IRM) pour le diagnostic de la maladie d’Alzheimer (MA). La première partie de ce travail consiste en une introduction générale sur la MA, l’IRM et les défis de l’apprentissage machine en imagerie médicale. Dans la deuxième partie de ce travail, je présente les trois articles composant la thèse. Enfin, la troisième partie porte sur une discussion des contributions et perspectives fu- tures de ce travail de recherche. Le premier article de cette thèse montre que l’agrégation des données sur plusieurs sites d’acquisition entraîne une certaine perte, comparative- ment à l’analyse sur un seul site, qui tend à diminuer plus la taille de l’échantillon aug- mente. Le deuxième article de cette thèse examine la généralisabilité des modèles de prédiction à l’aide de divers schémas de validation croisée. Les résultats montrent que la formation et les essais sur le même ensemble de sites surestiment la précision du modèle, comparativement aux essais sur des nouveaux sites. J’ai également montré que l’entraînement sur un grand nombre de sites améliore la précision sur des nouveaux sites. Le troisième et dernier article porte sur l’hétérogénéité des étiquettes cliniques et pro- pose un nouveau cadre dans lequel il est possible d’identifier un sous-groupe d’individus qui partagent une signature homogène hautement prédictive de la démence liée à la MA. Cette signature se retrouve également chez les patients présentant des symptômes mod- érés. Les résultats montrent que 90% des sujets portant la signature ont progressé vers la démence en trois ans. Les travaux de cette thèse apportent ainsi de nouvelles con- tributions à la manière dont nous approchons l’hétérogénéité en diagnostic médical et proposent des pistes de solution pour tirer profit de cette hétérogénéité.Computer assisted diagnosis has emerged as a popular area of research at the intersection of medical imaging and machine learning. Medical data are very heterogeneous in nature and therefore require careful attention when one wants to train prediction models. In this thesis, I explored two sources of heterogeneity, multisite aggregation and clinical label heterogeneity, in an application of magnetic resonance imaging to the diagnosis of Alzheimer’s disease. In the process, I learned about the feasibility of multisite data aggregation and how to leverage that heterogeneity in order to improve generalizability of prediction models. Part one of the document is a general context introduction to Alzheimer’s disease, magnetic resonance imaging, and machine learning challenges in medical imaging. In part two, I present my research through three articles (two published and one in preparation). Finally, part three provides a discussion of my contributions and hints to possible future developments. The first article shows that data aggregation across multiple acquisition sites incurs some loss, compared to single site analysis, that tends to diminish as the sample size increase. These results were obtained through semisynthetic Monte-Carlo simulations based on real data. The second article investigates the generalizability of prediction models with various cross-validation schemes. I showed that training and testing on the same batch of sites over-estimates the accuracy of the model, compared to testing on unseen sites. However, I also showed that training on a large number of sites improves the accuracy on unseen sites. The third article, on clinical label heterogeneity, proposes a new framework where we can identify a subgroup of individuals that share a homogeneous signature highly predictive of AD dementia. That signature could also be found in patients with mild symptoms, 90% of whom progressed to dementia within three years. The thesis thus makes new contributions to dealing with heterogeneity in medical diagnostic applications and proposes ways to leverage that heterogeneity to our benefit