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. ...

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 ...

Diffusion magnetic resonance imaging (dMRI) is currently the method of choice for the in vivo and non-invasive quantification of water diffusion in biological tissue. Several diffusion models have been proposed to obtain quantitative diffusion parameters, which have shown to provide novel information on the structural and organizational features of biological tissue, the brain white matter in particular. The goal of this dissertation is to improve the accuracy of the diffusion parameter estimation, given the non-Gaussian nature of the diffusion-weighted MR data. In part I of this manuscript, the necessary basics of dMRI are provided. Next, Part II deals with diffusion parameter estimation and includes the main contributions of the research. Finally, Part III covers the construction of a population-based dMRI atlas of the rat brain.

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 substrate of a complex dynamic system providing a remarkably varied range of functionalities, going from simple perception to higher-level cognition. Disturbances in its complex dynamics can cause an equally vast variety of mental disorders. One such brain disorder is schizophrenia, a neurodevelopmental disease characterized by abnormal perception of reality that manifests in symptoms like hallucinations or delusions. Even though the brain is known to be affected in schizophrenia, the exact pathophysiology underlying its developmental course is still mostly unknown. In this thesis, we develop and apply methods to look into ongoing brain function measured through magnetic resonance imaging (MRI) and evaluate the potential of these approaches for improving our understanding of psychosis vulnerability and schizophrenia. We focus on patients with chromosome 22q11.2 deletion syndrome (22q11DS), a genetic disorder that comes with a 30fold increased risk for ...

Nowadays, Nuclear Magnetic Resonance (NMR) is widely used in oncology as a non-invasive diagnostic tool in order to detect the presence of tumor regions in the human body. An application of NMR is Magnetic Resonance Imaging, which is applied in routine clinical practice to localize tumors and determine their size. Magnetic Resonance Imaging is able to provide an initial diagnosis, but its ability to delineate anatomical and pathological information is significantly improved by its combination with another NMR application, namely Magnetic Resonance Spectroscopy. The latter reveals information on the biochemical profile tissues, thereby allowing clinicians and radiologists to identify in a non{invasive way the different tissue types characterizing the sample under investigation, and to study the biochemical changes underlying a pathological situation. In particular, an NMR application exists which provides spatial as well as biochemical information. This application is called ...

Multiple sclerosis is a progressive autoimmune disease that a˙ects young adults. Magnetic resonance (MR) imaging has become an integral part in monitoring multiple sclerosis disease. Conventional MR imaging sequences such as fluid attenuated inversion recovery imaging have high spatial resolution, and can visualise the presence of focal white matter brain lesions in multiple sclerosis disease. Manual delineation of these lesions on conventional MR images is time consuming and su˙ers from intra and inter-rater variability. Among the advanced MR imaging techniques, MR spectroscopic imaging can o˙er complementary information on lesion characterisation compared to conventional MR images. However, MR spectroscopic images have low spatial resolution. Therefore, the aim of this thesis is to automatically segment multiple sclerosis lesions on conventional MR images and use the information from high-resolution conventional MR images to enhance the resolution of MR spectroscopic images. Automatic single time ...

Advances in wearable electrocardiogram (ECG) monitoring devices have allowed for new cardiovascular applications to emerge beyond diagnostics, such as stress and fatigue detection, athletic performance assessment, sleep disorder characterization, mood recognition, activity surveillance, biometrics, and fitness tracking, to name a few. Such devices, however, are prone to artifacts, particularly due to movement, thus hampering heart rate and heart rate variability measurement and posing a serious threat to cardiac monitoring applications. To address these issues, this thesis proposes the use of a spectro-temporal signal representation called “modulation spectrum”, which is shown to accurately separate cardiac and noise components from the ECG signals, thus opening doors for noise-robust ECG signal processing tools and applications. First, an innovative ECG quality index based on the modulation spectral signal representation is proposed. The representation quantifies the rate-of-change of ECG spectral components, which are shown to ...

Preterm birth is a major pediatric health problem that perturbs the genetically determined program of corticogenesis of the developing brain. As a consequence, prematurity has been strongly associated with adverse long-term neurodevelopmental outcome that may persist even into adulthood. Early characterization of the underlying neuronal mechanisms and early identification of infants at risk is of paramount importance since it allows better development of early therapeutic interventions aiming to prevent adverse outcomes through resilience. This dissertation aims to investigate the consequences of preterm birth on brain function and structure and their relation to adverse neurodevelopmental outcome, as well as to unveil the effect of an early music intervention on brain function. Research to date has mainly focused on the effect of early interventions on the long-term outcome but not on the effect of those interventions on brain function in preterm populations. ...

Epilepsy is a neurological condition that manifests in 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. Epilepsy cannot be cured and in many cases is not controlled by medication either. Surgical resection of the region responsible for generating the epileptic seizures might offer remedy for these patients. Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) measure the changes of brain activity in time over different locations of the brain. As such, they provide valuable information on the nature, the timing and the spatial origin of the epileptic activity. Unfortunately, both techniques record activity of different brain and artefact sources as well. Hence, EEG and fMRI signals are characterised by low signal to noise ratio. Data quality and the vast amount ...

Magnetic Resonance Spectroscopy (MRS) is a technique which has evolved rapidly over the past 15 years. It has been used specifically in the context of brain tumours and has shown very encouraging correlations between brain tumour type and spectral pattern. In vivo MRS enables the quantification of metabolite concentrations non-invasively, thereby avoiding serious risks to brain damage. While Magnetic Resonance Imaging (MRI) is commonly used for identifying the location and size of brain tumours, MRS complements it with the potential to provide detailed chemical information about metabolites present in the brain tissue and enable an early detection of abnormality. However, the introduction of MRS in clinical medicine has been difficult due to problems associated with the acquisition of in vivo MRS signals from living tissues at low magnetic fields acceptable for patients. The low signal-to-noise ratio makes accurate analysis of ...

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 ...

Intravascular ultrasound has, over the past decade, significantly changed the clinical diagnosis and therapeutic strategy of coronary and vascular disease assessment, as it not only allows visualisation of the vessel lumen, but gives a unique view of the pathophysiologic structure of the artery wall. This information is currently unavailable from the universally accepted instrument for artery assessment, angiography, which has on several occasions had its diagnostic accuracy questioned. With intravascular ultrasound, there is the potential to categorise diseased arterial tissue belonging to distinct pathological groups which can ultimately aid in the understanding of individual lesions as well as making a significant contribution to treatment choice and management of cardiac patients. The high resolution image information offered by intravascular ultrasound provides excellent crosssectional views of coronary artery disease at the level of the disease process itself. This information can be used ...

The necessity to process signals living in non-Euclidean domains, such as signals de- fined on the top of a graph, has led to the extension of signal processing techniques to the graph setting. Among different approaches, graph signal processing distinguishes it- self by providing a Fourier analysis of these signals. Analogously to the Fourier transform for time and image signals, the graph Fourier transform decomposes the graph signals in terms of the harmonics provided by the underlying topology. For instance, a graph signal characterized by a slow variation between adjacent nodes has a low frequency content. Along with the graph Fourier transform, graph filters are the key tool to alter the graph frequency content of a graph signal. This thesis focuses on graph filters that are performed distributively in the node domain–that is, each node needs to exchange in- formation ...

Every year, an estimated 15 million babies are born preterm, that is, before 37 weeks of gestation. This number is rising in all countries and currently represents more than 1 in 10 babies, affecting families all over the world. During the last decades, the survival rate of prematurely born neonates has steadily increased, mainly as a result of medical and technical progress in neonatal intensive care. The very preterm infants, which represent up to 10% of the preterm infants in the EU, remain at risk for adverse outcome and neurodevelopmental disability. These maladaptive outcomes have a severe effect on the children’s quality of life and a huge economic impact on society. In order to reduce this burden and improve neonatal care in general, appropriate tools need to be developed to identify the neonates with a higher risk of adverse outcomes. ...