Worldwide approximately 11% of the babies are born before 37 weeks of gestation. The survival rates of these prematurely born infants have steadily increased during the last decades as a result of the technical and medical progress in the neonatal intensive care units (NICUs). The focus of the NICUs has therefore gradually evolved from increasing life chances to improving quality of life. In this respect, promoting and supporting optimal brain development is crucial. Because these neonates are born during a period of rapid growth and development of the brain, they are susceptible to brain damage and therefore vulnerable to adverse neurodevelopmental outcome. In order to identify patients at risk of long-term disabilities, close monitoring of the neurological function during the first critical weeks is a primary concern in the current NICUs. Electroencephalography (EEG) is a valuable tool for continuous noninvasive ...

This thesis focuses on the design of various automatic signal processing algorithms to extract information from physiological signals of preterm infants. Overall, the aim was to improve the neurodevelopmental outcome of the neonate. More specifically, three main research objectives were carried out. The first objective was to describe the maturation of neonates during their stay in the neonatal intensive care unit. The second objective was to assess the stress and pain in premature infants and their impact on the development of neonates. The third objective was to predict developmental disabilities, such as autism. The first part of this thesis presents an extensive overview of various developmental models to describe the maturation of premature infants. Three main strategies were proposed. The first strategy proposed an investigation of EEG connectivity networks. A variety of functional and effective connectivity methods were combined with ...

Preterm birth is a major risk factor for neurodevelopment impairments often only appearing later in life. The brain is still at a high rate of development during adolescence, making this a promising window for intervention. It is thus crucial to understand the mechanisms of altered brain function in this population. The aim of this thesis is to investigate how the brain dynamically reconfigures its own organisation over time in preterm-born young adolescents. Research to date has mainly focused on structural disturbances or in static features of brain function in this population. However, recent studies have shown that brain activity is highly dynamic, both spontaneously and during performance of a task, and that small disruptions in its complex architecture may interfere with normal behaviour and cognitive abilities. This thesis explores the dynamic nature of brain function in preterm-born adolescents in three ...

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. ...

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 ...

Around 10 percent of all human births is premature, which means that annually about 15 million babies are born before 37 completed weeks of gestation. About one third of the admissions to the Neonatal Intensive Care Unit (NICU) consists of this patient group. Due to complications, 1 million babies die from premature delivery, and it is therefore the most important cause of neonatal death. In general, premature and immature babies have a high risk for neurological abnormalities by maturation in extra-uterine life. Even though improved health care has increased the survival changes of these neonates, they are sensitive to brain damage and consequently, neurocognitive disabilities. Nowadays, critical information about the brain development can be extracted from the electroencephalography (EEG). Clinical experts visually assess evolving EEG characteristics over both short and long periods to evaluate maturation of patients at risk and, ...

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 ...

All human actions involve motor control. Even the simplest movement requires the coordinated recruitment of many muscles, orchestrated by neuronal circuits in the brain and the spinal cord. As a consequence, lesions affecting the central nervous system, such as stroke, can lead to a wide range of motor impairments. While a certain degree of recovery can often be achieved by harnessing the plasticity of the motor hierarchy, patients typically struggle to regain full motor control. In this context, technology-assisted interventions offer the prospect of intense, controllable and quantifiable motor training. Yet, clinical outcomes remain comparable to conventional approaches, suggesting the need for a paradigm shift towards customized knowledge-driven treatments to fully exploit their potential. In this thesis, we argue that a detailed understanding of healthy and impaired motor pathways can foster the development of therapies optimally engaging plasticity. To this ...

Accounting for uncertainty in three-dimensional (3D) shapes is important in a large number of scientific and engineering areas, such as biometrics, biomedical imaging, and data mining. It is well known that 3D polar shaped objects can be represented by Fourier descriptors such as spherical harmonics and double Fourier series. However, the statistics of these spectral shape models have not been widely explored. This thesis studies several areas involved in 3D shape modeling, including random field models for statistical shape modeling, optimal shape filtering, parametric active contours for object segmentation and surface reconstruction. It also investigates multi-modal image registration with respect to tumor activity quantification. Spherical harmonic expansions over the unit sphere not only provide a low dimensional polarimetric parameterization of stochastic shape, but also correspond to the Karhunen-Lo´eve (K-L) expansion of any isotropic random field on the unit sphere. Spherical ...

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 ...

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 ...

Cardiovascular diseases are a growing problem in today’s society. The World Health Organization (WHO) reported that these diseases make up about 30% of total global deaths and that heart diseases have no geographic, gender or socioeconomic boundaries. Therefore, detecting cardiac irregularities early-stage and a correct treatment are very important. However, this requires a good physiological understanding of the cardiovascular system. The heart is stimulated electrically by the brain via the autonomic nervous system, where sympathetic and vagal pathways are always interacting and modulating heart rate. Continuous monitoring of the heart activity is obtained by means of an ElectroCardioGram (ECG). Studying the fluctuations of heart beat intervals over time reveals a lot of information and is called heart rate variability (HRV) analysis. A reduction of HRV has been reported in several cardiological and noncardiological diseases. Moreover, HRV also has a prognostic ...

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 ...

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 ...

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 ...