A Method for Unsupervised Semi-Quantification of Inmunohistochemical Staining with Beta Divergences

In many research laboratories, it is essential to determine the relative expression levels of some proteins of interest in tissue samples. The semi-quantitative scoring of a set of images consists of establishing a scale of scores ranging from zero or one to a maximum number set by the researcher and assigning a score to each image that should represent some predefined characteristic of the IHC staining, such as its intensity. However, manual scoring depends on the judgment of an observer and therefore exposes the assessment to a certain level of bias. In this work, we present a fully automatic and unsupervised method for comparative biomarker quantification in histopathological brightfield images. The method relies on a color separation method that discriminates between two chromogens expressed as brown and blue colors robustly, independent of color variation or biomarker expression level. For this purpose, we have adopted a two-stage stain separation approach in the optical density space. First, a preliminary separation is performed using a deconvolution method in which the color vectors of the stains are determined after an eigendecomposition of the data. Then, we adjust the separation using the non-negative matrix factorization method with beta divergences, initializing the algorithm with the matrices resulting from the previous step. After that, a feature vector of each image based on the intensity of the two chromogens is determined. Finally, the images are annotated using a systematically initialized k-means clustering algorithm with beta divergences. The method clearly defines the initial boundaries of the categories, although some flexibility is added. Experiments for the semi-quantitative scoring of images in five categories have been carried out by comparing the results with the scores of four expert researchers yielding accuracies that range between 76.60% and 94.58%. These results show that the proposed automatic scoring system, which is definable and reproducible, produces consistent results.FEDER / Junta de Andalucía-Consejería de Economía y Conocimiento US-1264994Fondo de Desarrollo (FEDER). Unión Europea PGC2018-096244-B-I00, SAF2016-75442-RMinisterio de Economía, Industria y Competitividad (MINECO). España TEC2017- 82807-

Information Theoretic Approaches for Motor-Imagery BCI Systems: Review and Experimental Comparison

Brain computer interfaces (BCIs) have been attracting a great interest in recent years. The common spatial patterns (CSP) technique is a well-established approach to the spatial filtering of the electroencephalogram (EEG) data in BCI applications. Even though CSP was originally proposed from a heuristic viewpoint, it can be also built on very strong foundations using information theory. This paper reviews the relationship between CSP and several information-theoretic approaches, including the Kullback–Leibler divergence, the Beta divergence and the Alpha-Beta log-det (AB-LD)divergence. We also revise other approaches based on the idea of selecting those features that are maximally informative about the class labels. The performance of all the methods will be also compared via experiments.Gobierno Español MICINN TEC2014-53103-

EEG Signal Processing in Motor Imagery Brain Computer Interfaces with Improved Covariance Estimators

Desde hace unos años hasta la actualidad, el desarrollo en el campo de los interfaces cerebro ordenador ha ido aumentando. Este aumento viene motivado por una serie de factores distintos. A medida que aumenta el conocimiento acerca del cerebro humano y como funciona (del que aún se conoce relativamente poco), van surgiendo nuevos avances en los sistemas BCI que, a su vez, sirven de motivación para que se investigue más acerca de este órgano. Además, los sistemas BCI abren una puerta para que cualquier persona pueda interactuar con su entorno independientemente de la discapacidad física que pueda tener, simplemente haciendo uso de sus pensamientos. Recientemente, la industria tecnológica ha comenzado a mostrar su interés por estos sistemas, motivados tanto por los avances con respecto a lo que conocemos del cerebro y como funciona, como por el uso constante que hacemos de la tecnología en la actuali- dad, ya sea a través de nuestros smartphones, tablets u ordenadores, entre otros muchos dispositivos. Esto motiva que compañías como Facebook inviertan en el desarrollo de sistemas BCI para que tanto personas sin discapacidad como aquellas que, si las tienen, puedan comunicarse con los móviles usando solo el cerebro. El trabajo desarrollado en esta tesis se centra en los sistemas BCI basados en movimien- tos imaginarios. Esto significa que el usuario piensa en movimientos motores que son interpretados por un ordenador como comandos. Las señales cerebrales necesarias para traducir posteriormente a comandos se obtienen mediante un equipo de EEG que se coloca sobre el cuero cabelludo y que mide la actividad electromagnética producida por el cere- bro. Trabajar con estas señales resulta complejo ya que son no estacionarias y, además, suelen estar muy contaminadas por ruido o artefactos. Hemos abordado esta temática desde el punto de vista del procesado estadístico de la señal y mediante algoritmos de aprendizaje máquina. Para ello se ha descompuesto el sistema BCI en tres bloques: preprocesado de la señal, extracción de características y clasificación. Tras revisar el estado del arte de estos bloques, se ha resumido y adjun- tado un conjunto de publicaciones que hemos realizado durante los últimos años, y en las cuales podemos encontrar las diferentes aportaciones que, desde nuestro punto de vista, mejoran cada uno de los bloques anteriormente mencionados. De manera muy resumida, para el bloque de preprocesado proponemos un método mediante el cual conseguimos nor- malizar las fuentes de las señales de EEG. Al igualar las fuentes efectivas conseguimos mejorar la estima de las matrices de covarianza. Con respecto al bloque de extracción de características, hemos conseguido extender el algoritmo CSP a casos no supervisados. Por último, en el bloque de clasificación también hemos conseguido realizar una sepa- ración de clases de manera no supervisada y, por otro lado, hemos observado una mejora cuando se regulariza el algoritmo LDA mediante un método específico para Gaussianas.The research and development in the field of Brain Computer Interfaces (BCI) has been growing during the last years, motivated by several factors. As the knowledge about how the human brain is and works (of which we still know very little) grows, new advances in BCI systems are emerging that, in turn, serve as motivation to do more re- search about this organ. In addition, BCI systems open a door for anyone to interact with their environment regardless of the physical disabilities they may have, by simply using their thoughts. Recently, the technology industry has begun to show its interest in these systems, mo- tivated both by the advances about what we know of the brain and how it works, and by the constant use we make of technology nowadays, whether it is by using our smart- phones, tablets or computers, among many other devices. This motivates companies like Facebook to invest in the development of BCI systems so that people (with or without disabilities) can communicate with their devices using only their brain. The work developed in this thesis focuses on BCI systems based on motor imagery movements. This means that the user thinks of certain motor movements that are in- terpreted by a computer as commands. The brain signals that we need to translate to commands are obtained by an EEG device that is placed on the scalp and measures the electromagnetic activity produced by the brain. Working with these signals is complex since they are non-stationary and, in addition, they are usually heavily contaminated by noise or artifacts. We have approached this subject from the point of view of statistical signal processing and through machine learning algorithms. For this, the BCI system has been split into three blocks: preprocessing, feature extraction and classification. After reviewing the state of the art of these blocks, a set of publications that we have made in recent years has been summarized and attached. In these publications we can find the different contribu- tions that, from our point of view, improve each one of the blocks previously mentioned. As a brief summary, for the preprocessing block we propose a method that lets us nor- malize the sources of the EEG signals. By equalizing the effective sources, we are able to improve the estimation of the covariance matrices. For the feature extraction block, we have managed to extend the CSP algorithm for unsupervised cases. Finally, in the classification block we have also managed to perform a separation of classes in an blind way and we have also observed an improvement when the LDA algorithm is regularized by a specific method for Gaussian distributions