Disturbances in cerebral hemodynamics are one of the principal causes of cerebral damage in premature infants. Specifically, changes in cerebral blood flow might cause ischemia or hemorrhage that can lead to motor and developmental disabilities. Under normal circumstances, there are several mechanisms that act jointly to preserve cerebral hemodynamics homeostasis. However, in case that one of these mechanisms is disrupted the brain is exposed to damage. Premature infants are susceptible to variations in cerebral circulation due to their fragility. Therefore, monitoring cerebral hemodynamics is of vital importance in order to prevent brain damage in this population and avoid subsequent sequelae. This thesis is oriented to the development of signal processing techniques that can be of help in monitoring cerebral hemodynamics in neonates. There are several problems that hinder the use in clinical practice of monitoring cerebral hemodynamics. On one hand, ...

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 ...

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. ...

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 ...

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, ...

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 ...

This work has, as its objective, the development of non-invasive and low-cost systems for monitoring and automatic diagnosing specific neonatal diseases by means of the analysis of suitable video signals. We focus on monitoring infants potentially at risk of diseases characterized by the presence or absence of rhythmic movements of one or more body parts. Seizures and respiratory diseases are specifically considered, but the approach is general. Seizures are defined as sudden neurological and behavioural alterations. They are age-dependent phenomena and the most common sign of central nervous system dysfunction. Neonatal seizures have onset within the 28th day of life in newborns at term and within the 44th week of conceptional age in preterm infants. Their main causes are hypoxic-ischaemic encephalopathy, intracranial haemorrhage, and sepsis. Studies indicate an incidence rate of neonatal seizures of 2‰ live births, 11‰ for preterm ...

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 ...

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 ...

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 ...

Functional near infrared spectroscopy (fNIRS) needs a standardization in signal processing tools before it is recognized as a reliable neuroimaging modality. This thesis study tries to present a comprehensive analysis of the feasibility of applying statistical inference methods to fNIRS signals. Using hierarchical linear models, both classical and Bayesian techniques are pursued and performance of different methods are presented on a comparative basis. The results obtained from a set of cognitive signals show that fNIRS can identify cognitive activity both at the subject and group levels. The analysis suggests that mixed or Bayesian hierarchical models are especially convenient for fNIRS signals. A related problem that is discussed in this thesis study is to guarantee that the outcome of the statistical analysis is congruent with underlying physiology. This problem is studied by putting constraints over the parameters to be estimated. Carrying ...

Nowadays, diagnosis and treatment of brain tumors is based on clinical symptoms, radiological appearance, and often histopathology. Magnetic resonance imaging (MRI) is a major noninvasive tool for the anatomical assessment of tumors in the brain. However, several diagnostic questions, such as the type and grade of the tumor, are difficult to address using MRI. The histopathology of a tissue specimen remains the gold standard, despite the associated risks of surgery to obtain a biopsy. In recent years, the use of magnetic resonance spectroscopy (MRS), which provides a metabolic profile, has gained a lot of interest for a more detailed and specific noninvasive evaluation of brain tumors. In particular, magnetic resonance spectroscopic imaging (MRSI) is attractive as this may also enable to visualize the heterogeneous spatial extent of tumors, both inside and outside the MRI detectable lesion. As manual, individual, viewing ...

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 ...