Learning Vector Quantization with Applications in Neuroimaging and Biomedicine

An early clinical diagnosis of neurodegenerative diseases is complex and not always possible due to overlapping characteristics between the disorders. Biomarkers are necessary and functional brain imaging may provide a solution. Generally, machine learning can aid the diagnosis, but the decision process of some methods cannot always be understood. Furthermore, machine learning requires data. Therefore, functional brain scans from several neuroimaging centers are combined into a single dataset. We show that this leads to unwanted variation in the data that can inflate the performance of machine learning.Learning Vector Quantization is a type of machine learning that produces a prototypical representation (prototypes) of the classes in the data. Additionally, it weights the input space based on its relevance to the classification task. In one application example, we train a model on steroid measurements from patients with a benign or malignant adrenocortical tumor. In this case, the obtained models were directly interpretable and helped to decide between different measuring technologies.Due to the complex nature of the brain data, the models trained to diagnose neurodegenerative diseases are not directly understandable. Nonetheless, we show that prototypes and relevances can be reconstructed in the imaging space, increasing the interpretability of the models significantly. Additionally, we can produce easy-to-understand representations of the data that can visualize the diagnosis and progression over time of patients, leading to actionable scenarios. Lastly, we present a novel method to deal with center-related, unwanted variance in the data

FDG-PET combined with learning vector quantization allows classification of neurodegenerative diseases and reveals the trajectory of idiopathic REM sleep behavior disorder

Background and Objectives 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with principal component analysis (PCA) has been applied to identify disease-related brain patterns in neurodegenerative disorders such as Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD). These patterns are used to quantify functional brain changes at the single subject level. This is especially relevant in determining disease progression in idiopathic REM sleep behavior disorder (iRBD), a prodromal stage of PD and DLB. However, the PCA method is limited in discriminating between neurodegenerative conditions. More advanced machine learning algorithms may provide a solution. In this study, we apply Generalized Matrix Learning Vector Quantization (GMLVQ) to FDG-PET scans of healthy controls, and patients with AD, PD and DLB. Scans of iRBD patients, scanned twice with an approximate 4 year interval, were projected into GMLVQ space to visualize their trajectory. Methods We applied a combination of SSM/PCA and GMLVQ as a classifier on FDG-PET data of healthy controls, AD, DLB, and PD patients. We determined the diagnostic performance by performing a ten times repeated ten fold cross validation. We analyzed the validity of the classification system by inspecting the GMLVQ space. First by the projection of the patients into this space. Second by representing the axis, that span this decision space, into a voxel map. Furthermore, we projected a cohort of RBD patients, whom have been scanned twice (approximately 4 years apart), into the same decision space and visualized their trajectories. Results The GMLVQ prototypes, relevance diagonal, and decision space voxel maps showed metabolic patterns that agree with previously identified disease-related brain patterns. The GMLVQ decision space showed a plausible quantification of FDG-PET data. Distance traveled by iRBD subjects through GMLVQ space per year (i.e. velocity) was correlated with the change in motor symptoms per year (Spearman’s rho =0.62, P=0.004). Conclusion In this proof-of-concept study, we show that GMLVQ provides a classification of patients with neurodegenerative disorders, and may be useful in future studies investigating speed of progression in prodromal disease stages

Machine Learning Based Analysis of FDG-PET Image Data for the Diagnosis of Neurodegenerative Diseases

Alzheimer's disease (AD) and Parkinson's disease (PD) are two common, progressive neurodegenerative brain disorders. Their diagnosis is very challenging at an early disease stage, if based on clinical symptoms only. Brain imaging techniques such as [18F]-fluoro-deoxyglucose positron emission tomography (FDG-PET) can provide important additional information with respect to changes in the cerebral glucose metabolism. In this study, we use machine learning techniques to perform an automated classification of FDG-PET data. The approach is based on the extraction of features by applying the scaled subprofile model with principal component analysis (SSM/PCA) in order to extract characteristics patterns of glucose metabolism. These features are then used for discriminating healthy controls, PD and AD patients by means of two machine learning frameworks: Generalized Matrix Learning Vector Quantization (GMLVQ) with local and global relevance matrices, and Support Vector Machines (SVMs) with a linear kernel. Datasets from different neuroimaging centers are considered. Results obtained for the individual centers, show that reliable classification is possible. We demonstrate, however, that cross-center classification can be problematic due to potential center-specific characteristics of the available FDG-PET data

Prediction of neurodegenerative diseases from functional brain imaging data

Neurodegenerative diseases are a challenge, especially in the developed society where life expectancy is high. Since these diseases progress slowly, they are not easy to diagnose at an early stage. Moreover, they portray similar disease features, which makes them hard to differentiate. In this thesis, the objective was to devise techniques to extract biomarkers from brain data for the prediction and classification of neurodegenerative diseases, in particular parkinsonian syndromes. We used principal component analysis in combination with the scaled subprofile model to extract features from the brain data to classify these disorders. Thereafter, the features were provided to several classifiers, i.e., decision trees, generalized matrix learning vector quantization, and support vector machine to classify the parkinsonian syndromes. A validation of the classifiers was performed. The decision tree method was compared to the stepwise regression method which aims at linearly combining a few good principal components. The stepwise regression method performed better than the decision tree method in the classification of the parkinsonian syndromes. Combining the two methods is feasible. The decision trees helped us to visualize the classification results, hence providing an insight into the distribution of features. Both generalized matrix learning vector quantization and support vector machine are better than the decision tree method in the classification of early-stage parkinsonian syndromes. All the classification methods used in this thesis performed well with later disease stage data. We conclude that generalized matrix learning vector quantization and decision tree methods can be recommended for further research on neurodegenerative disease classification and prediction

Integration of Auxiliary Data Knowledge in Prototype Based Vector Quantization and Classification Models

This thesis deals with the integration of auxiliary data knowledge into machine learning methods especially prototype based classification models. The problem of classification is diverse and evaluation of the result by using only the accuracy is not adequate in many applications. Therefore, the classification tasks are analyzed more deeply. Possibilities to extend prototype based methods to integrate extra knowledge about the data or the classification goal is presented to obtain problem adequate models. One of the proposed extensions is Generalized Learning Vector Quantization for direct optimization of statistical measurements besides the classification accuracy. But also modifying the metric adaptation of the Generalized Learning Vector Quantization for functional data, i. e. data with lateral dependencies in the features, is considered.:Symbols and Abbreviations 1 Introduction 1.1 Motivation and Problem Description . . . . . . . . . . . . . . . . . 1 1.2 Utilized Data Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2 Prototype Based Methods 19 2.1 Unsupervised Vector Quantization . . . . . . . . . . . . . . . . . . 22 2.1.1 C-means . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.1.2 Self-Organizing Map . . . . . . . . . . . . . . . . . . . . . . 25 2.1.3 Neural Gas . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 2.1.4 Common Generalizations . . . . . . . . . . . . . . . . . . . 30 2.2 Supervised Vector Quantization . . . . . . . . . . . . . . . . . . . . 35 2.2.1 The Family of Learning Vector Quantizers - LVQ . . . . . . 36 2.2.2 Generalized Learning Vector Quantization . . . . . . . . . 38 2.3 Semi-Supervised Vector Quantization . . . . . . . . . . . . . . . . 42 2.3.1 Learning Associations by Self-Organization . . . . . . . . . 42 2.3.2 Fuzzy Labeled Self-Organizing Map . . . . . . . . . . . . . 43 2.3.3 Fuzzy Labeled Neural Gas . . . . . . . . . . . . . . . . . . 45 2.4 Dissimilarity Measures . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.4.1 Differentiable Kernels in Generalized LVQ . . . . . . . . . 52 2.4.2 Dissimilarity Adaptation for Performance Improvement . 56 3 Deeper Insights into Classification Problems - From the Perspective of Generalized LVQ- 81 3.1 Classification Models . . . . . . . . . . . . . . . . . . . . . . . . . . 81 3.2 The Classification Task . . . . . . . . . . . . . . . . . . . . . . . . . 84 3.3 Evaluation of Classification Results . . . . . . . . . . . . . . . . . . 88 3.4 The Classification Task as an Ill-Posed Problem . . . . . . . . . . . 92 4 Auxiliary Structure Information and Appropriate Dissimilarity Adaptation in Prototype Based Methods 93 4.1 Supervised Vector Quantization for Functional Data . . . . . . . . 93 4.1.1 Functional Relevance/Matrix LVQ . . . . . . . . . . . . . . 95 4.1.2 Enhancement Generalized Relevance/Matrix LVQ . . . . 109 4.2 Fuzzy Information About the Labels . . . . . . . . . . . . . . . . . 121 4.2.1 Fuzzy Semi-Supervised Self-Organizing Maps . . . . . . . 122 4.2.2 Fuzzy Semi-Supervised Neural Gas . . . . . . . . . . . . . 123 5 Variants of Classification Costs and Class Sensitive Learning 137 5.1 Border Sensitive Learning in Generalized LVQ . . . . . . . . . . . 137 5.1.1 Border Sensitivity by Additive Penalty Function . . . . . . 138 5.1.2 Border Sensitivity by Parameterized Transfer Function . . 139 5.2 Optimizing Different Validation Measures by the Generalized LVQ 147 5.2.1 Attention Based Learning Strategy . . . . . . . . . . . . . . 148 5.2.2 Optimizing Statistical Validation Measurements for Binary Class Problems in the GLVQ . . . . . . . . . . . . . 155 5.3 Integration of Structural Knowledge about the Labeling in Fuzzy Supervised Neural Gas . . . . . . . . . . . . . . . . . . . . . . . . . 160 6 Conclusion and Future Work 165 My Publications 168 A Appendix 173 A.1 Stochastic Gradient Descent (SGD) . . . . . . . . . . . . . . . . . . 173 A.2 Support Vector Machine . . . . . . . . . . . . . . . . . . . . . . . . 175 A.3 Fuzzy Supervised Neural Gas Algorithm Solved by SGD . . . . . 179 Bibliography 182 Acknowledgements 20

Epilepsy

With the vision of including authors from different parts of the world, different educational backgrounds, and offering open-access to their published work, InTech proudly presents the latest edited book in epilepsy research, Epilepsy: Histological, electroencephalographic, and psychological aspects. Here are twelve interesting and inspiring chapters dealing with basic molecular and cellular mechanisms underlying epileptic seizures, electroencephalographic findings, and neuropsychological, psychological, and psychiatric aspects of epileptic seizures, but non-epileptic as well

Implementing decision tree-based algorithms in medical diagnostic decision support systems

As a branch of healthcare, medical diagnosis can be defined as finding the disease based on the signs and symptoms of the patient. To this end, the required information is gathered from different sources like physical examination, medical history and general information of the patient. Development of smart classification models for medical diagnosis is of great interest amongst the researchers. This is mainly owing to the fact that the machine learning and data mining algorithms are capable of detecting the hidden trends between features of a database. Hence, classifying the medical datasets using smart techniques paves the way to design more efficient medical diagnostic decision support systems. Several databases have been provided in the literature to investigate different aspects of diseases. As an alternative to the available diagnosis tools/methods, this research involves machine learning algorithms called Classification and Regression Tree (CART), Random Forest (RF) and Extremely Randomized Trees or Extra Trees (ET) for the development of classification models that can be implemented in computer-aided diagnosis systems. As a decision tree (DT), CART is fast to create, and it applies to both the quantitative and qualitative data. For classification problems, RF and ET employ a number of weak learners like CART to develop models for classification tasks. We employed Wisconsin Breast Cancer Database (WBCD), Z-Alizadeh Sani dataset for coronary artery disease (CAD) and the databanks gathered in Ghaem Hospital’s dermatology clinic for the response of patients having common and/or plantar warts to the cryotherapy and/or immunotherapy methods. To classify the breast cancer type based on the WBCD, the RF and ET methods were employed. It was found that the developed RF and ET models forecast the WBCD type with 100% accuracy in all cases. To choose the proper treatment approach for warts as well as the CAD diagnosis, the CART methodology was employed. The findings of the error analysis revealed that the proposed CART models for the applications of interest attain the highest precision and no literature model can rival it. The outcome of this study supports the idea that methods like CART, RF and ET not only improve the diagnosis precision, but also reduce the time and expense needed to reach a diagnosis. However, since these strategies are highly sensitive to the quality and quantity of the introduced data, more extensive databases with a greater number of independent parameters might be required for further practical implications of the developed models

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Redes neuronales y preprocesado de variables para modelos y sensores en bioingeniería

El propósito de esta Tesis Doctoral es proponer una alternativa viable a la aproximación de modelos y procesos en el ámbito científico y, más concretamente, en aplicaciones complejas de bioingeniería, en las cuales es imposible o muy costoso encontrar una relación directa entre las señales de entrada y de salida mediante modelos matemáticos sencillos o aproximaciones estadísticas. Del mismo modo, es interesante lograr una compactación de los datos que necesita un modelo para conseguir una predicción o clasificación en un tiempo y con un coste de implementación mínimos. Un modelo puede ser simplificado en gran medida al reducir el número de entradas o realizar operaciones matemáticas sobre éstas para transformarlas en nuevas variables. En muchos problemas de regresión (aproximación de funciones), clasificación y optimización, en general se hace uso de las nuevas metodologías basadas en la inteligencia artificial. La inteligencia artificial es una rama de las ciencias de la computación que busca automatizar la capacidad de un sistema para responder a los estímulos que recibe y proponer salidas adecuadas y racionales. Esto se produce gracias a un proceso de aprendizaje, mediante el cual se presentan ciertas muestras o �ejemplos� al modelo y sus correspondientes salidas y éste aprende a proponer las salidas correspondientes a nuevos estímulos que no ha visto previamente. Esto se denomina aprendizaje supervisado. También puede darse el caso de que tal modelo asocie las entradas con características similares entre sí para obtener una clasificación de las muestras de entrada sin necesidad de un patrón de salida. Este modelo de aprendizaje se denomina no supervisado. El principal exponente de la aplicación de la inteligencia artificial para aproximación de funciones y clasificación son las redes neuronales artificiales. Se trata de modelos que han demostrado sobradamente sus ventajas en el ámbito del modelado estadístico y de la predicción frente a otros métodos clásicos. NMateo Jiménez, F. (2012). Redes neuronales y preprocesado de variables para modelos y sensores en bioingeniería [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/16702Palanci