A complex physical system like the human brain can only be comprehended by the use of a combination of various medical imaging techniques, each of which shed light on only a specific aspect of the neural processes that take place beneath the skull. Electroencephalography (EEG) and functional magnetic resonance (fMRI) are two such modalities, which enable the study of brain (dys)function. While the EEG is measured with a limited set of scalp electrodes which record rapid electrical changes resulting from neural activity, fMRI offers a superior spatial resolution at the expense of only picking up slow fluctuations of oxygen concentration that takes place near active brain cells. Hence, combining these very complementary modalities is an appealing, but complicated task due to their heterogeneous nature. In this thesis, we devise advanced signal processing techniques which integrate the multimodal data stemming from ...

The brain is the most important signal processing unit in the human body. It is responsible for receiving, processing and storing information. One of the possibilities to study brain functioning is by placing electrodes on the scalp and recording the synchronous neuronal activity of the brain. Such a recording measures a combination of active processes in the whole brain. Unfortunately, it is also contaminated by artifacts. By extracting the artifacts and removing them, cleaned recordings can be investigated. Furthermore, it is easier to look at specific brain activities, like an epileptic seizure, than at a combination. In this thesis, we present different mathematical techniques that can be used to extract individual contributing sources from the measured signals for this purpose. We focused on Canonical Correlation Analysis (CCA), Independent Component Analysis (ICA) and Canonical/ Parallel Factor Analysis (CPA). We show that ...

The growing interest in neuroimaging technologies generates a massive amount of biomedical data that exhibit high dimensionality. Tensor-based analysis of brain imaging data has by now been recognized as an effective approach exploiting its inherent multi-way nature. In particular, the advantages of tensorial over matrix-based methods have previously been demonstrated in the context of functional magnetic resonance imaging (fMRI) source localization; the identification of the regions of the brain which are activated at specific time instances. However, such methods can also become ineffective in realistic challenging scenarios, involving, e.g., strong noise and/or significant overlap among the activated regions. Moreover, they commonly rely on the assumption of an underlying multilinear model generating the data. In the first part of this thesis, we aimed at investigating the possible gains from exploiting the 3-dimensional nature of the brain images, through a higher-order tensorization ...

Understanding the cognitive processes that are going on in the human brain, requires the combination of several types of observations. For this reason, since several years, neuroscience research started to focus on multimodal approaches. One such multimodal approach is the combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). The non-invasive character of these two modalities makes their combination not only harmless and painless, but also especially suited for widespread research in both clinical and experimental applications. Moreover, the complementarity between the high temporal resolution of the EEG and the high spatial resolution of the fMRI, allows obtaining a more complete picture of the processes under study. However, the combination of EEG and fMRI is challenging, not only on the level of the data acquisition, but also when it comes to extracting the activity of interest and interpreting the ...

A key issue in understanding how the brain functions is the ability to correlate functional information with anatomical localisation. Functional information can be provided by a variety of techniques like positron emission tomography (PET), functional MRI (fMRI), electroencephalography (EEG), magnetoencephalography (MEG) or transcranial magnetic stimulation (TMS). All these methods provide different, but complementary, information about the functional areas of the brain. PET and fMRI provide spatially accurate picture of brain regions involved in a given task. TMS permits to infer the contribution of the stimulated brain area to the task under investigation. EEG and MEG, which reflects brain activity directly, have temporal accuracy of the order of a millisecond. TMS, EEG and MEG are offset by their low spatial resolution. In this thesis, we propose two methods to improve the spatial accuracy of method based on TMS and EEG. The ...

Magnetic Resonance Imaging (MRI) constitutes a non-invasive medical imaging technique that allows the exploration of the inner anatomy, tissues, and physiological processes of the body. Among the different MRI applications, functional Magnetic Resonance Imaging (fMRI) has slowly become an essential tool for investigating the brain behavior and, nowadays, it plays a fundamental role in clinical and neurophysiological research. Due to its particular nature, specialized signal processing techniques are required in order to analyze the fMRI data properly. Among the various related techniques that have been developed over the years, the General Linear Model (GLM) is one of the most widely used approaches, and it usually appears as a default in many specialized software toolboxes for fMRI. On the other end, Blind Source Separation (BSS) methods constitute the most common alternative to GLM, especially when no prior information regarding the brain ...

Localizing the bioelectric phenomena originating from the cerebral cortex and evoked by auditory and somatosensory stimuli are clear objectives to both understand how the brain works and to recognize different pathologies. Diseases such as Parkinson's, Alzheimer's, schizophrenia and epilepsy are intensively studied to find a cure or accurate diagnosis. Epilepsy is considered the disease with major prevalence within disorders with neurological origin. The recurrent and sudden incidence of seizures can lead to dangerous and possibly life-threatening situations. Since disturbance of consciousness and sudden loss of motor control often occur without any warning, the ability to predict epileptic seizures would reduce patients' anxiety, thus considerably improving quality of life and safety. The common procedure for epilepsy seizure detection is based on brain activity monitorization via electroencephalogram (EEG) data. This process consumes a lot of time, especially in the case of long ...

Most cognitive processes in the brain are reflected through several aspects simultaneously, allowing us to observe the same process from different biological phenomena. The diverse nature of these biological processes suggests that a better understanding of cerebral activity may be achieved through multimodal measurements. One of the possible multimodal brain recording settings is the combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), which is one of the main topics of this thesis. Two groups of EEG-fMRI integration approaches are possible. The first group, commonly called model-based techniques, are very popular due to the fact that the results from such analyses confirm or disprove a specific hypothesis. However, such hypotheses are not always available, requiring a more explorative approach to analyze the data. This exploration is possible with the second group of approaches, the so-called data-driven methods. The data-driven ...

Brain function requires a continuous flow of oxygen and glucose. An insufficient supply for a few minutes during the first period of life may have severe consequences or even result in death. This happens in one to six infants per 1000 live term births. Therefore, there is a high need for a method which can enable bedside brain monitoring to identify those neonates at risk and be able to start the treatment in time. The most important currently available technology to continuously monitor brain function is electroEncephaloGraphy (or EEG). Unfortunately, visual EEG analysis requires particular skills which are not always present round the clock in the Neonatal Intensive Care Unit (NICU). Even if those skills are available it is laborsome to manually analyse many hours of EEG. The lack of time and skill are the main reasons why EEG is ...

Epilepsy is one of the most common neurological diseases that manifests in repetitive epileptic seizures as a result of an abnormal, synchronous activity of a large group of neurons. Depending on the affected brain regions, seizures produce various severe clinical symptoms. There is no cure for epilepsy and sometimes even medication and other therapies, like surgery, vagus nerve stimulation or ketogenic diet, do not control the number of seizures. In that case, long-term (home) monitoring and automatic seizure detection would enable the tracking of the evolution of the disease and improve objective insight in any responses to medical interventions or changes in medical treatment. Especially during the night, supervision is reduced; hence a large number of seizures is missed. In addition, an alarm should be integrated into the automated seizure detection algorithm for severe seizures in order to help the ...

Standard signal processing techniques are implicitly based on the assumption that the signal lies on a regular, homogeneous domain. In practice, however, many signals lie on an irregular or inhomogeneous domain. An application area where data are naturally defined on an irregular or inhomogeneous domain is human brain neuroimaging. The goal in neuroimaging is to map the structure and function of the brain using imaging techniques. In particular, functional magnetic resonance imaging (fMRI) is a technique that is conventionally used in non-invasive probing of human brain function. This doctoral dissertation deals with the development of signal processing schemes that adapt to the domain of the signal. It consists of four papers that in different ways deal with exploiting knowledge of the signal domain to enhance the processing of signals. In each paper, special focus is given to the analysis of ...

Gliomas represent about 80% of all malignant primary brain tumors. Despite recent advancements in glioma research, patient outcome remains poor. The 5 year survival rate of the most common and most malignant subtype, i.e. glioblastoma, is about 5%. Magnetic resonance imaging (MRI) has become the imaging modality of choice in the management of brain tumor patients. Conventional MRI (cMRI) provides excellent soft tissue contrast without exposing the patient to potentially harmful ionizing radiation. Over the past decade, advanced MRI modalities, such as perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) have gained interest in the clinical field, and their added value regarding brain tumor diagnosis, treatment planning and follow-up has been recognized. Tumor segmentation involves the imaging-based delineation of a tumor and its subcompartments. In gliomas, segmentation plays an important role in treatment planning as well ...

This research focuses on the development of algorithms to extract diagnostic information from the ECG signal, which can be used to improve automatic detection systems and home monitoring solutions. In the first part of this work, a generically applicable algorithm for model selection in kernel principal component analysis is presented, which was inspired by the derivation of respiratory information from the ECG signal. This method not only solves a problem in biomedical signal processing, but more importantly offers a solution to a long-standing problem in the field of machine learning. Next, a methodology to quantify the level of contamination in a segment of ECG is proposed. This level is used to detect artifacts, and to improve the performance of different classifiers, by removing these artifacts from the training set. Furthermore, an evaluation of three different methodologies to compute the ECG-derived ...

In this thesis, the power of Machine Learning (ML) algorithms is combined with brain connectivity patterns, using Magnetic Resonance Imaging (MRI), for classification and prediction of Multiple Sclerosis (MS). White Matter (WM) as well as Grey Matter (GM) graphs are studied as connectome data types. The thesis addresses three main research objectives. The first objective aims to generate realistic brain connectomes data for improving the classification of MS clinical profiles in cases of data scarcity and class imbalance. To solve the problem of limited and imbalanced data, a Generative Adversarial Network (GAN) was developed for the generation of realistic and biologically meaningful connec- tomes. This network achieved a 10% better MS classification performance compared to classical approaches. As second research objective, we aim to improve classification of MS clinical profiles us- ing morphological features only extracted from GM brain tissue. ...

Over the last decades, Magnetic Resonance Imaging (MRI) has taken a leading role in the study of human body and it is widely used in clinical diagnosis. In vivo and ex vivo Magnetic Resonance Spectroscopic (MRS) techniques can additionally provide valuable metabolic information as compared to MRI and are gaining more clinical interest. The analysis of MRS data is a complex procedure and requires several preprocessing steps aiming to improve the quality of the data and to extract the most relevant features before any classification algorithm can be successfully applied. In this thesis a new approach to quantify magnetic resonance spectroscopic imaging (MRSI) data and therefore to obtain improved metabolite estimates is proposed. Then an important part is focusing on improving the diagnosis of glial brain tumors which are characterized by an extensive heterogeneity since various intramural histopathological properties such ...