Super Resolution of HARDI images Using Compressed Sensing Techniques

Effective techniques of inferring the condition of neural tracts in the brain is invaluable for clinicians and researchers towards investigation of neurological disorders in patients. It was not until the advent of diffusion Magnetic Resonance Imaging (dMRI), a noninvasive imaging method used to detect the diffusion of water molecules, that scientists have been able to assess the characteristics of cerebral diffusion in vivo. Among different dMRI methods, High Angular Resolution Diffusion Imaging (HARDI) is well known for striking a balance between ability to distinguish crossing neural fibre tracts while requiring a modest number of diffusion measurements (which is directly related to acquisition time). HARDI data provides insight into the directional properties of water diffusion in cerebral matter as a function of spatial coordinates. Ideally, one would be interested in having this information available at fine spatial resolution while minimizing the probing along different spatial orientations (so as to minimize the acquisition time). Unfortunately, availability of such datasets in reasonable acquisition times are hindered by limitations in current hardware and scanner protocols. On the other hand, post processing techniques prove promising in increasing the effective spatial resolution, allowing more detailed depictions of cerebral matter, while keeping the number of diffusion measurements within a feasible range. In light of the preceding developments, the main purpose of this research is to look into super resolution of HARDI data, using the modern theory of compressed sensing. The method proposed in this thesis allows an accurate approximation of HARDI signals at a higher spatial resolution compared to data obtained with a typical scanner. At the same time, ideas for reducing the number of diffusion measurements in the angular domain to improve the acquisition time are explored. Accordingly, the novel method of applying two distinct compressed sensing approaches in both spatial and angular domain, and combining them into a single framework for performing super resolution forms the main contribution provided by this thesis

Combined brain language connectivity and intraoperative neurophysiologic techniques in awake craniotomy for eloquent-area brain tumor resection

Speech processing can be disturbed by primary brain tumors (PBT). Improvement of presurgical planning techniques decrease neurological morbidity associated to tumor resection during awake craniotomy. The aims of this work were: 1. To perform Diffusion Kurtosis Imaging based tractography (DKI-tract) in the detection of brain tracts involved in language; 2. To investigate which factors contribute to functional magnetic resonance imaging (fMRI) maps in predicting eloquent language regional reorganization; 3. To determine the technical aspects of accelerometric (ACC) recording of speech during surgery. DKI-tracts were streamlined using a 1.5T magnetic resonance scanner. Number of tracts and fiber pathways were compared between DKI and standard Diffusion Tensor Imaging (DTI) in healthy subjects (HS) and PBT patients. fMRI data were acquired using task-specific and resting-state paradigms during language and motor tasks. After testing intraoperative fMRI’s influence on direct cortical stimulation (DCS) number of stimuli, graph-theory measures were extracted and analyzed. Regarding speech recording, ACC signals were recorded after evaluating neck positions and filter bandwidths. To test this method, language disturbances were recorded in patients with dysphonia and after applying DCS in the inferior frontal gyrus. In contrast, HS reaction time was recorded during speech execution. DKI-tract showed increased number of arcuate fascicle tracts in PBT patients. Lower spurious tracts were identified with DKI-tract. Intraoperative fMRI and DCS showed similar stimuli in comparison with DCS alone. Increased local centrality accompanied language ipsilateral and contralateral reorganization. ACC recordings showed minor artifact contamination when placed at the suprasternal notch using a 20-200 Hz filter bandwidth. Patients with dysphonia showed decreased amplitude and frequency in comparison with HS. ACC detected an additional 11% disturbances after DCS, and a shortening of latency within the presence of a loud stimuli during speech execution. This work improved current knowledge on presurgical planning techniques based on brain structural and functional neuroimaging connectivity, and speech recordingA função linguística do ser humano pode ser afetada pela presença de tumores cerebrais (TC) A melhoria de técnicas de planeamento pré-cirurgico diminui a morbilidade neurológica iatrogénica associada ao seu tratamento cirúrgico. O objetivo deste trabalho é: 1. Testar a fiabilidade da tractografia estimada por difusor de kurtose (tract-DKI), dos feixes cerebrais envolvidos na linguagem 2. Identificar os fatores que contribuem para o mapeamento linguagem por ressonância magnética funcional (RMf) na predição da neuroplasticidade. 3. Identificar aspetos técnicos do registo da linguagem por accelerometria (ACC). A DKI-tract foi estimada após realização de RM cerebral com 1.5T. O número e percurso das fibras foi avaliado. A RMf foi adquirida durante realização de tarefas linguísticas, motoras, e em repouso. Foi testada influência dos mapas de ativação calculados por RMf, no número de estímulos realizados durante a estimulação direta cortical (EDC) intraoperatória. Medidas de conectividade foram extraídas de regiões cerebrais. A posição e filtragem de sinal ACC foram estudadas após vocalização de palavras. O sinal ACC obtido em voluntários foi comparado com doentes disfónicos, após estimulação do giro inferior frontal, e após a adição de um estímulo sonoro perturbador durante vocalização. A tract-DKI estimou um elevado número de fascículos do feixe arcuato com menos falsos negativos. Os mapas linguísticos de RMf intraoperatória, não influenciou a EDC. Medidas de centralidade aumentaram após neuroplasticidade ipsilateral e contralateral. A posição supraesternal e a filtragem de sinal ACC entre 20-200Hz demonstrou menor ruido de contaminação. Este método identificou diminuição de frequência e amplitude em doentes com disfonia, 11% de erros linguísticos adicionais após estimulação e diminuição do tempo de latência quando presente o sinal sonoro perturbador. Este trabalho promoveu a utilização de novas técnicas no planeamento pré-cirúrgico do doente com tumor cerebral e alterações da linguagem através do estudo de conectividade estrutural, funcional e registo da linguagem

Anatomo-functional magnetic resonance imaging of the spinal cord and its application to the characterization of spinal lesions in cats

Les lésions de la moelle épinière ont un impact significatif sur la qualité de la vie car elles peuvent induire des déficits moteurs (paralysie) et sensoriels. Ces déficits évoluent dans le temps à mesure que le système nerveux central se réorganise, en impliquant des mécanismes physiologiques et neurochimiques encore mal connus. L'ampleur de ces déficits ainsi que le processus de réhabilitation dépendent fortement des voies anatomiques qui ont été altérées dans la moelle épinière. Il est donc crucial de pouvoir attester l'intégrité de la matière blanche après une lésion spinale et évaluer quantitativement l'état fonctionnel des neurones spinaux. Un grand intérêt de l'imagerie par résonance magnétique (IRM) est qu'elle permet d'imager de façon non invasive les propriétés fonctionnelles et anatomiques du système nerveux central. Le premier objectif de ce projet de thèse a été de développer l'IRM de diffusion afin d'évaluer l'intégrité des axones de la matière blanche après une lésion médullaire. Le deuxième objectif a été d'évaluer dans quelle mesure l'IRM fonctionnelle permet de mesurer l'activité des neurones de la moelle épinière. Bien que largement appliquées au cerveau, l'IRM de diffusion et l'IRM fonctionnelle de la moelle épinière sont plus problématiques. Les difficultés associées à l'IRM de la moelle épinière relèvent de sa fine géométrie (environ 1 cm de diamètre chez l'humain), de la présence de mouvements d'origine physiologique (cardiaques et respiratoires) et de la présence d'artefacts de susceptibilité magnétique induits par les inhomogénéités de champ, notamment au niveau des disques intervertébraux et des poumons. L'objectif principal de cette thèse a donc été de développer des méthodes permettant de contourner ces difficultés. Ce développement a notamment reposé sur l'optimisation des paramètres d'acquisition d'images anatomiques, d'images pondérées en diffusion et de données fonctionnelles chez le chat et chez l'humain sur un IRM à 3 Tesla. En outre, diverses stratégies ont été étudiées afin de corriger les distorsions d'images induites par les artefacts de susceptibilité magnétique, et une étude a été menée sur la sensibilité et la spécificité de l'IRM fonctionnelle de la moelle épinière. Les résultats de ces études démontrent la faisabilité d'acquérir des images pondérées en diffusion de haute qualité, et d'évaluer l'intégrité de voies spinales spécifiques après lésion complète et partielle. De plus, l'activité des neurones spinaux a pu être détectée par IRM fonctionnelle chez des chats anesthésiés. Bien qu'encourageants, ces résultats mettent en lumière la nécessité de développer davantage ces nouvelles techniques. L'existence d'un outil de neuroimagerie fiable et robuste, capable de confirmer les paramètres cliniques, permettrait d'améliorer le diagnostic et le pronostic chez les patients atteints de lésions médullaires. Un des enjeux majeurs serait de suivre et de valider l'effet de diverses stratégies thérapeutiques. De telles outils représentent un espoir immense pour nombre de personnes souffrant de traumatismes et de maladies neurodégénératives telles que les lésions de la moelle épinière, les tumeurs spinales, la sclérose en plaques et la sclérose latérale amyotrophique.Spinal cord injury has a significant impact on quality of life since it can lead to motor (paralysis) and sensory deficits. These deficits evolve in time as reorganisation of the central nervous system occurs, involving physiological and neurochemical mechanisms that are still not fully understood. Given that both the severity of the deficit and the successful rehabilitation process depend on the anatomical pathways that have been altered in the spinal cord, it may be of great interest to assess white matter integrity after a spinal lesion and to evaluate quantitatively the functional state of spinal neurons. The great potential of magnetic resonance imaging (MRI) lies in its ability to investigate both anatomical and functional properties of the central nervous system non invasively. To address the problem of spinal cord injury, this project aimed to evaluate the benefits of diffusion-weighted MRI to assess the integrity of white matter axons that remain after spinal cord injury. The second objective was to evaluate to what extent functional MRI can measure the activity of neurons in the spinal cord. Although widely applied to the brain, diffusion-weighted MRI and functional MRI of the spinal cord are not straightforward. Various issues arise from the small cross-section width of the cord, the presence of cardiac and respiratory motions, and from magnetic field inhomogeneities in the spinal region. The main purpose of the present thesis was therefore to develop methodologies to circumvent these issues. This development notably focused on the optimization of acquisition parameters to image anatomical, diffusion-weighted and functional data in cats and humans at 3T using standard coils and pulse sequences. Moreover, various strategies to correct for susceptibility-induced distortions were investigated and the sensitivity and specificity in spinal cord functional MRI was studied. As a result, acquisition of high spatial and angular diffusion-weighted images and evaluation of the integrity of specific spinal pathways following spinal cord injury was achieved. Moreover, functional activations in the spinal cord of anaesthetized cats was detected. Although encouraging, these results highlight the need for further technical and methodological development in the near-future. Being able to develop a reliable neuroimaging tool for confirming clinical parameters would improve diagnostic and prognosis. It would also enable to monitor the effect of various therapeutic strategies. This would certainly bring hope to a large number of people suffering from trauma and neurodegenerative diseases such as spinal cord injury, tumours, multiple sclerosis and amyotrophic lateral sclerosis

Development of Advanced, Clinically Feasible Neuroimaging Methodology with Diffusional Kurtosis Imaging

Diffusion MRI (dMRI) is a powerful, non-invasive tool for probing the structural organization of the human brain. Quantitative dMRI analyses provide unique capabilities for the characterization of tissue microstructure as well as imaging contrast that is not available to other modalities. White matter tractography relies on dMRI and is currently the only non-invasive technique for mapping structural connections in the human brain. In this chapter, we will describe diffusional kurtosis imaging, an effective and versatile dMRI technique, and discuss a clinical problem in temporal lobe epilepsy (TLE) which is insurmountable with current diagnostic approaches. Subsequent chapters will further develop the capabilities of DKI and demonstrate how it may be particularly well suited to overcome current barriers to care in the clinical management of TLE

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Advanced MRI methods for probing disease severity and functional decline in multiple sclerosis

Multiple sclerosis (MS) is a chronic and severe disease of the central nervous system characterized by complex pathology including inflammatory demyelination and neurodegeneration. MS impacts >2.8 million people worldwide, with most starting with a relapsing-remitting form (RRMS) in young adulthood, and many of them worsening to a secondary-progressive course (SPMS) despite treatment. So, there is a clear need for improved disease characterization. MRI is an ideal tool for non-invasive assessment of MS pathology, but there is still no established measure of disease activity and functional consequences. This project aims to overcome the challenge by developing novel imaging measures based on brain diffusion MRI and phase congruency texture analysis of conventional MRI. Through advanced modeling and analysis of clinically feasible brain MRI, this thesis investigates whether and how the derived measures differentiate MS pathology types and disease severity and predict functional outcomes in MS. The overall process has led to important technical innovations in several aspects. These include: innovative modeling of simple diffusion acquisitions to generate high angular resolution diffusion imaging (HARDI) measures; new optimization and harmonization techniques for diffusion MRI; innovative neural network models to create new diffusion data for comprehensive HARDI modeling; and novel methods and a graphic user interface for optimizing phase congruency analyses. Assisted by different machine learning methods, collective findings show that advanced measures from both diffusion MRI and phase congruency are highly sensitive to subtle differences in MS pathology, which differentiate disease severity between RRMS and SPMS through multi-dimensional analyses including chronic active lesions, and predict functional outcomes especially in physical and neurocognitive domains. These results are clinically translational and the new measures and techniques can help improve the evaluation and management of both MS and similar diseases

Models and analysis of vocal emissions for biomedical applications: 5th International Workshop: December 13-15, 2007, Firenze, Italy

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies. The Workshop has the sponsorship of: Ente Cassa Risparmio di Firenze, COST Action 2103, Biomedical Signal Processing and Control Journal (Elsevier Eds.), IEEE Biomedical Engineering Soc. Special Issues of International Journals have been, and will be, published, collecting selected papers from the conference

Characterisation of the Haemodynamic Response Function (HRF) in the neonatal brain using functional MRI

Background: Preterm birth is associated with a marked increase in the risk of later neurodevelopmental impairment. With the incidence rising, novel tools are needed to provide an improved understanding of the underlying pathology and better prognostic information. Functional Magnetic Resonance Imaging (fMRI) with Blood Oxygen Level Dependent (BOLD) contrast has the potential to add greatly to the knowledge gained through traditional MRI techniques. However, it has been rarely used with neonatal subjects due to difficulties in application and inconsistent results. Central to this is uncertainity regarding the effects of early brain development on the Haemodynamic Response Function (HRF), knowledge of which is fundamental to fMRI methodology and analysis. Hypotheses: (1) Well localised and positive BOLD functional responses can be identified in the neonatal brain. (2) The morphology of the neonatal HRF differs significantly during early human development. (3) The application of an age-appropriate HRF will improve the identification of functional responses in neonatal fMRI studies. Methods: To test these hypotheses, a systematic fMRI study of neonatal subjects was carried out using a custom made somatosensory stimulus, and an adapted study design and analysis pipeline. The neonatal HRF was then characterised using an event related study design. The potential future application of the findings was then tested in a series of small experiments. Results: Well localised and positive BOLD functional responses were identified in neonatal subjects, with a maturational tendency towards an increasingly complex pattern of activation. A positive amplitude HRF was identified in neonatal subjects, with a maturational trend of a decreasing time-to-peak and increasing positive peak amplitude. Application of the empirical HRF significantly improved the precision of analysis in further fMRI studies. Conclusions: fMRI can be used to study functional activity in the neonatal brain, and may provide vital new information about both development and pathology