Ensembles of Deep Learning Architectures for the Early Diagnosis of the Alzheimer’s Disease.

Computer Aided Diagnosis (CAD) constitutes an important tool for the early diagnosis of Alzheimer’s Disease (AD), which, in turn, allows the application of treatments that can be simpler and more likely to be effective. This paper explores the construction of classification methods based on deep learning architectures applied on brain regions defined by the Automated Anatomical Labeling (AAL). Gray Matter (GM) images from each brain area have been split into 3D patches according to the regions defined by the AAL atlas and these patches are used to train different deep belief networks. An ensemble of deep belief networks is then composed where the final prediction is determined by a voting scheme. Two deep learning based structures and four different voting schemes are implemented and compared, giving as a result a potent classification architecture where discriminative features are computed in an unsupervised fashion. The resulting method has been evaluated using a large dataset from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Classification results assessed by cross-validation prove that the proposed method is not only valid for differentiate between controls (NC) and AD images, but it also provides good performances when tested for the more challenging case of classifying Mild Cognitive Impairment (MCI) Subjects. In particular, the classification architecture provides accuracy values up to 0.90 and AUC of 0.95 for NC/AD classification, 0.84 and AUC of 0.91 for stable MCI/AD classification and 0.83 and AUC of 0.95 for NC/MCI converters classification.This work was partly supported by the MICINN un der the projects TEC2012-34306 and PSI2015-65848- R, and the Consejer´ıa de Innovaci´on, Ciencia y Em presa (Junta de Andaluc´ıa, Spain) under the Ex cellence Projects P09-TIC-4530, P11-TIC-7103 and the Universidad de M´alaga. Programa de fortalec imiento de las capacidades de I+D+I en las Uni versidades 2014-2015, de la Consejer´ıa de Econom´ıa, Innovaci´on, Ciencia y Empleo, cofinanciado por el fondo europeo de desarrollo regional (FEDER) un der the project FC14-SAF30. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Ini tiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bio engineering, and through generous contributions from the following: AbbVie, Alzheimer’s Associa tion; Alzheimer’s Drug Discovery Foundation; Ara clon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Eu roImmun; F. Hoffmann-La Roche Ltd and its affili ated company Genentech, Inc.; Fujirebio; GE Health care; IXICO Ltd.; Janssen Alzheimer Immunother apy Research & Development, LLC.;Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity ; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Re search is providing funds to support ADNI clinical sites in Canada. Private sector contributions are fa cilitated by the Foundation for the National Insti tutes of Health (www.fnih.org). The grantee organi zation is the Northern California Institute for Re search and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California

Enhancing Multimodal Patterns in Neuroimaging by Siamese Neural Networks with Self-Attention Mechanism.

The combination of different sources of information is currently one of the most relevant aspects in the diagnostic process of several diseases. In the field of neurological disorders, different imaging modalities providing structural and functional information are frequently available. Those modalities are usually analyzed separately, although a joint of the features extracted from both sources can improve the classification performance of Computer-aided diagnosis (CAD) tools. Previous studies have computed independent models from each individual modality and combined then in a subsequent stage, which is not an optimum solution. In this work, we propose a method based on the principles of siamese neural networks to fuse information from Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). This framework quantifies the similarities between both modalities and relates them with the diagnostic label during the training process. The resulting latent space at the output of this network is then entered into an attention module in order to evaluate the relevance of each brain region and modality at different stages of the development of Alzheimer’s disease. The excellent results obtained and the high flexibility of the method proposed allows fusing more than two modalities, leading to a scalable methodology that can be used in a wide range of contexts.This work was supported by projects PGC2018- 098813-B-C32 and RTI2018-098913-B100 (Spanish “Ministerio de Ciencia, Innovación y Universidades”), UMA20-FEDERJA-086, A-TIC-080- UGR18 and P20 00525 (Consejería de economía y conocimiento, Junta de Andalucía) and by European Regional Development Funds (ERDF); and by Spanish “Ministerio de Universidades” through Margarita-Salas grant to J.E. Arco

Deep Residual Transfer Learning for Automatic Diabetic Retinopathy Grading.

Evaluation and diagnosis of retina pathology is usually made via the analysis of different image modalities that allow to explore its structure. The most popular retina image method is retinography, a technique that displays the fundus of the eye, including the retina and other structures. Retinography is the most common imaging method to diagnose retina diseases such as Diabetic Retinopathy (DB) or Macular Edema (ME). However, retinography evaluation to score the image according to the disease grade presents difficulties due to differences in contrast, brightness and the presence of artifacts. Therefore, it is mainly done via manual analysis; a time consuming task that requires a trained clinician to examine and evaluate the images. In this paper, we present a computer aided diagnosis tool that takes advantage of the performance provided by deep learning architectures for image analysis. Our proposal is based on a deep residual convolutional neural network for extracting discriminatory features with no prior complex image transformations to enhance the image quality or to highlight specific structures. Moreover, we used the transfer learning paradigm to reuse layers from deep neural networks previously trained on the ImageNet dataset, under the hypothesis that first layers capture abstract features than can be reused for different problems. Experiments using different convolutional architectures have been carried out and their performance has been evaluated on the MESSIDOR database using cross-validation. Best results were found using a ResNet50-based architecture, showing an AUC of 0.93 for grades 0 + 1, AUC of 0.81 for grade 2 and AUC of 0.92 for grade 3 labelling, as well as AUCs higher than 0.97 when considering a binary classification problem (grades 0 vs 3).This work was partly supported by the MINECO/FEDER under TEC2015-64718-R, RTI2018-098913-B-I00, PSI2015-65848-R and PGC2018-098813-B-C32 projects. We gratefully acknowledge the support of NVIDIA Cor poration with the donation of one of the GPUs used for this research. Work by F.J.M.M. was supported by the MICINN “Juan de la Cierva - Formacion” Fellowship

Empirical Functional PCA for 3D Image Feature Extraction Through Fractal Sampling.

Medical image classification is currently a challenging task that can be used to aid the diagnosis of different brain diseases. Thus, exploratory and discriminative analysis techniques aiming to obtain representative features from the images play a decisive role in the design of effective Computer Aided Diagnosis (CAD) systems, which is especially important in the early diagnosis of dementia. In this work, we present a technique that allows using specific time series analysis techniques with 3D images. This is achieved by sampling the image using a fractal-based method which preserves the spatial relationship among voxels. In addition, a method called Empirical functional PCA (EfPCA) is presented, which combines Empirical Mode Decomposition (EMD) with functional PCA to express an image in the space spanned by a basis of empirical functions, instead of using components computed by a predefined basis as in Fourier or Wavelet analysis. The devised technique has been used to classify images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Parkinson Progression Markers Initiative (PPMI), achieving accuracies up to 93% and 92% differential diagnosis tasks (AD versus controls and PD versus Controls, respectively). The results obtained validate the method, proving that the information retrieved by our methodology is significantly linked to the diseases.This work was partly supported by the MINECO/ FEDER under TEC2015-64718-R and PSI2015- 65848-R projects and the Consejer´ıa de Innovaci´on, Ciencia y Empresa (Junta de Andaluc´ıa, Spain) under the Excellence Project P11-TIC-7103 as well as the Salvador deMadariaga Mobility Grants 2017. Data collection and sharing for this project was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Depart ment of Defense award number W81XWH-12-2- 0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contribu tions from the following: AbbVie, Alzheimer’s Asso ciation; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol Myer Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Ho mann-La Roche Ltd and its ali ated company Genentech, Inc.; Fujirebio; GE Health care; IXICO Ltd.; Janssen Alzheimer Immunother apy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; P zer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clin ical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coor dinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern Cali fornia. PPMI a public-private partnership is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including [list the full names of all of the PPMI funding partners found at www.ppmi-info.org/fundingpartners]

Label Aided Deep Ranking for the Automatic Diagnosis of Parkinsonian Syndromes.

Parkinsonism is the second most common neurodegenerative disease in the world. Its diagnosis usually relies on visual analysis of Emission Computed Tomography (SPECT) images acquired using 123I − io f lupane radiotracer. This aims to detect a deficit of dopamine transporters at the striatum. The use of Computer Aided tools for diagnosis based on statistical data processing and machine learning methods have significantly improved the diagnosis accuracy. In this paper we propose a classification method based on Deep Ranking which learns an embedding function that projects the source images into a new space in which samples belonging to the same class are closer to each other, while samples from different classes are moved apart. Moreover, the proposed approach introduces a new cost-sensitive loss function to avoid overfitting due to class imbalance (an usual issue in practical biomedical applications), along with label information to produce sparser embedding spaces. The experiments carried out in this work demonstrate the superiority of the proposed method, improving the diagnosis accuracy achieved by previous methodologies and validate our approach as an efficient way to construct linear classifiers.This work was partly supported by the MINECO/FEDER under TEC2015-64718- R and PSI2015-65848-R projects. We gratefully acknowledge the support of NVIDIA Corporation with the donation of one of the GPUs used for this research. PPMI - a pub435 lic - private partnership - is funded by The Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbott, Biogen Idec, F. Hoffman-La Roche Ltd., GE Healthcare, Genentech and Pfizer Inc

Ensemble of random forests One vs. Rest classifiers for MCI and AD prediction using ANOVA cortical and subcortical feature selection and partial least squares.

Background: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly and affects approximately 30 million individuals worldwide. Mild cognitive impairment (MCI) is very frequently a prodromal phase of AD, and existing studies have suggested that people with MCI tend to progress to AD at a rate of about 10 % to 15 % per year. However, the ability of clinicians and machine learning systems to predict AD based on MRI biomarkers at an early stage is still a challenging problem that can have a great impact in improving treatments. Method: The proposed system, developed by the SiPBA-UGR team for this challenge, is based on feature standardization, ANOVA feature selection, partial least squares feature dimension reduction and an ensemble of one vs. rest random forest classifiers. With the aim of improving its performance when discriminating healthy controls (HC) from MCI, a second binary classification level was introduced that reconsiders the HC and MCI predictions of the first level. Results: The system was trained and evaluated on an ADNI datasets that consist of T1-weighted MRI morphological measurements from HC, stable MCI, converter MCI and AD subjects. The proposed system yields a 56.25 % classification score on the test subset which consists of 160 real subjects. Comparison with Existing Method(s): The classifier yielded the best performance when compared to: i) One vs. One (OvO), One vs. Rest (OvR) and error correcting output codes (ECOC) as strategies for reducing the multiclass classification task to multiple binary classification problems, ii) support vector machines, gradient boosting classifier and random forest as base binary classifiers, and iii) bagging ensemble learning. Conclusions: A robust method has been proposed for the international challenge on MCI prediction based on MRI data.This work was supported by the MINECO/FEDER under TEC2015-64718-R project, the Consejería de Economía, Innovacion, Ciencia, y Empleo of the Junta de Andalucía under the P11-TIC-7103 Excellence Project and the Salvador de Madariaga Mobility Grants 2017

Morphological Characterization of Functional Brain Imaging by Isosurface Analysis in Parkinson’s Disease.

Finding new biomarkers to model Parkinson’s Disease (PD) is a challenge not only to help discerning between Healthy Control (HC) subjects and patients with potential PD, but also as a way to measure quantitatively the loss of dopaminergic neurons mainly concentrated at substantia nigra. Within this context, the work presented here tries to provide a set of imaging features based on morphological characteristics extracted from I[123]-Ioflupane SPECT scans to discern between HC and PD participants in a balanced set of 386 scans from Parkinson’s Progression Markers Initiative (PPMI) database. These features, obtained from isosurfaces of each scan at different intensity levels, have been classified through the use of classical Machine Learning classifiers such as Support-Vector-Machines (SVM) or Na¨ıve Bayesian and compared with the results obtained using a Multi-Layer Perceptron (MLP). The proposed system, based on a Mann-Whitney-Wilcoxon U-Test for feature selection and the SVM approach, yielded a 97.04% balanced accuracy when the performance was evaluated using a 10-fold cross-validation. This proves the reliability of these biomarkers, especially those related to sphericity, center of mass, number of vertices, 2D-projected perimeter or the 2D-projected eccentricity; among others, but including both internal and external isosurfaces.This work was supported by the MINECO/FEDER under the RTI2018-098913-B-I00 and PGC2018- 098813-B-C32 projects and the General Secretariat of Universities, Research and Technology, Junta de Andalucía under the Excellence FEDER Project ATIC-117-UGR18

Procesos de ruido interno en los circuitos electrónicos. Técnicas de computación de la estabilidad de la frecuencia

La presente obra tiene por fin principal mostrar los resultados que arroja el proyecto de investigación nacional DPI2003-00878 en ejecución por los autores y financiado por el Ministerio de Ciencia y Tecnología de España (en el año 2003). Agradecemos a la Secretaría de Estado de Política Científica y Tecnológica (Dirección General de Investigación) la confianza depositada en el equipo investigador. El título del proyecto financiado es: “Técnicas de Computación en Equipos Electrónicos de Instrumentación para la Caracterización de la Estabilidad en Frecuencia de Fuentes Electrónicas de Precisión en Ambientes de Confluencia de Múltiples Tipos de Ruido”. La duración de este proyecto abarca el periodo del 1 de diciembre de 2003 al 30 de noviembre de 2006. Durante su ejecución se han revisado aspectos múltiples y pluridisciplinares, que constituyen la base de conocimientos adquiridos y expuestos en el presente documento. En líneas generales, en este proyecto se trata el problema del efecto del ruido interno en los circuitos electrónicos, analizando la problemática de la estabilidad en frecuencia. Esta magnitud física está involucrada en los equipos de comunicaciones, por lo que la caracterización de su estabilidad es un factor crítico. Una frecuencia poco estable hace que la temporización de eventos en un equipo electrónico sea poco fiable. Asimismo, la generación se señales es de baja calidad si el oscilador de referencia es poco estable. En general, la inestabilidad (a corto plazo) de una medida es provocada fundamentalmente por el efecto del ruido interno. El necesario repasar el concepto de “trazabilidad” con el fin de conocer el proceso de calibración de estos equipos. También se analizan cualitativamente los estándares en frecuencia. Los efectos del ruido sobre los circuitos electrónicos se caracterizan mediante las densidades espectrales de ruido (DER) evaluadas en la salida. Esto supone el empleo frecuente de diagramas logarítmicos. Para la obtención de las DER de salida se requiere el empleo del “Principio de Inversión” y el análisis de circuitos electrónicos basados en el amplificador operacional. Este se considera con sus Emitaciones prácticas en el dominio de la frecuencia. Así, una vez planteado el problema, descritos los estándares, y modelado y anaEzado el efecto del ruido sobre los circuitos electrónicos, se diferencia entre offset de frecuencia (desviación en frecuencia) y estabilidad en frecuencia. Esta última característica es el objeto del resto de la obra, empleándose la “varianza Ae Alian” como estimador de la estabilidad. Posteriormente se estudia el procedimiento de interpretación de las curvas de estabilidad y su traslación entre los dominios del tiempo y de la frecuencia. Para ello se emplean en primer lugar ejemplos deterministas y, posteriormente, procesos aleatorios. A lo largo del libro se pone de manifiesto el empleo de receptores GPS1 en el proceso trazable de cabbración y se muestra en el laboratorio un ejemplo. Queremos finalizar indicando que esta obra supone una entrega de los avances producidos en el presente proyecto de investigación. Los sucesivos progresos incrementarán los contenidos del presente trabajo

Using XAI in the Clock Drawing Test to reveal the cognitive impairment pattern.

he prevalence of dementia is currently increasing worldwide. This syndrome produces a deteriorationin cognitive function that cannot be reverted. However, an early diagnosis can be crucial for slowing itsprogress. The Clock Drawing Test (CDT) is a widely used paper-and-pencil test for cognitive assessmentin which an individual has to manually draw a clock on a paper. There are a lot of scoring systems forthis test and most of them depend on the subjective assessment of the expert. This study proposes acomputer-aided diagnosis (CAD) system based on artificial intelligence (AI) methods to analyze the CDTand obtain an automatic diagnosis of cognitive impairment (CI). This system employs a preprocessingpipeline in which the clock is detected, centered and binarized to decrease the computational burden.Then, the resulting image is fed into a Convolutional Neural Network (CNN) to identify the informativepatterns within the CDT drawings that are relevant for the assessment of the patient’s cognitive status.Performance is evaluated in a real context where patients with CI and controls have been classified byclinical experts in a balanced sample size of 3282 drawings. The proposed method provides an accuracyof 75.65% in the binary case-control classification task, with an AUC of 0.83. These results are indeedrelevant considering the use of the classic version of the CDT. The large size of the sample suggests thatthe method proposed has a high reliability to be used in clinical contexts and demonstrates the suitabilityof CAD systems in the CDT assessment process. Explainable artificial intelligence (XAI) methods areapplied to identify the most relevant regions during classification. Finding these patterns is extremelyhelpful to understand the brain damage caused by CI. A validation method using resubstitution withupper bound correction in a machine learning approach is also discusseThis work was supported by the MCIN/ AEI/10.13039/501100011033/ and FEDER “Una manera de hacer Europa” under the RTI2018- 098913-B100 project, by the Consejeria de Economia, Innovacion, Ciencia y Empleo (Junta de An765 dalucia) and FEDER under CV20-45250, A-TIC080-UGR18, B-TIC-586-UGR20 and P20-00525 projects, and by the Ministerio de Universidades under the FPU18/04902 grant given to C. JimenezMesa and the Margarita-Salas grant to J.E. Arco

Granger Causality-based Information Fusion Applied to Electrical Measurements from Power Transformers.

In the immediate future, with the increasing presence of electrical vehicles and the large increase in the use of renewable energies, it will be crucial that distribution power networks are managed, supervised and exploited in a similar way as the transmission power systems were in previous decades. To achieve this, the underlying infrastructure requires automated monitoring and digitization, including smart-meters, wide-band communication systems, electronic device based-local controllers, and the Internet of Things. All of these technologies demand a huge amount of data to be curated, processed, interpreted and fused with the aim of real-time predictive control and supervision of medium/low voltage transformer substations. Wiener–Granger causality, a statistical notion of causal inference based on Information Fusion could help in the prediction of electrical behaviour arising from common causal dependencies. Originally developed in econometrics, it has successfully been applied to several fields of research such as the neurosciences and is applicable to time series data whereby cause precedes effect. In this paper, we demonstrate the potential of this methodology in the context of power measures for providing theoretical models of low/medium power transformers. Up to our knowledge, the proposed method in this context is the first attempt to build a data-driven power system model based on G-causality. In particular, we analysed directed functional connectivity of electrical measures providing a statistical description of observed responses, and identified the causal structure within data in an exploratory analysis. Pair-wise conditional G-causality of power transformers, their independent evolution in time, and the joint evolution in time and frequency are discussed and analysed in the experimental section.This work was partly supported by the MINECO/ FEDER under the RTI2018- 098913-B100 project. The authors would like to acknowledge the support of 370 CDTI (Centro para el Desarrollo Tecnologico Industrial, Ministerio de Cien cia, Innovacion y Universidades and FEDER, SPAIN) under the PASTORA project (Ref.: ITC-20181102). and to thank the companies within the PAS TORA consortium: Endesa, Ayesa, Ormaz´abal and Ingelectus. We would like to thank the reviewers for their thoughtful comments and efforts towards im 375 proving our manuscript. Finally, JM Gorriz would like to thank Dr G´omez Exp´osito for his helpful advice and comments