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Abdullah, Bassem A. "Segmentation of Multiple Sclerosis Lesions in Brain MRI". Scholarly Repository, 2012. http://scholarlyrepository.miami.edu/oa_dissertations/711.
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Multiple Sclerosis (MS) is an autoimmune disease of central nervous system. It may result in a variety of symptoms from blurred vision to severe muscle weakness and degradation, depending on the affected regions in brain. To better understand this disease and to quantify its evolution, magnetic resonance imaging (MRI) is increasingly used nowadays. Manual delineation of MS lesions in MR images by human expert is time-consuming, subjective, and prone to inter-expert variability. Therefore, automatic segmentation is needed as an alternative to manual segmentation. However, the progression of the MS lesions shows considerable variability and MS lesions present temporal changes in shape, location, and area between patients and even for the same patient, which renders the automatic segmentation of MS lesions a challenging problem. In this dissertation, a set of segmentation pipelines are proposed for automatic segmentation of multiple sclerosis (MS) lesions from brain magnetic resonance imaging (MRI) data. These techniques use a trained support vector machine (SVM) to discriminate between the blocks in regions of MS lesions and the blocks in non-MS lesion regions mainly based on the textural features with aid of the other features. The main contribution of this set of frameworks is the use of textural features to detect MS lesions in a fully automated approach that does not rely on manually delineating the MS lesions. In addition, the technique introduces the concept of the multi-sectional views segmentation to produce verified segmentation. The multi-sectional views pipeline is customized to provide better segmentation performance and to benefit from the properties and the nature of MS lesion in MRI. These customization and enhancement leads to development of the customized MV-T-SVM. The MRI datasets that were used in the evaluation of the proposed pipelines are simulated MRI datasets (3 subjects) generated using the McGill University BrainWeb MRI Simulator, real datasets (51 subjects) publicly available at the workshop of MS Lesion Segmentation Challenge 2008 and real MRI datasets (10 subjects) for MS subjects acquired at the University of Miami. The obtained results indicate that the proposed method would be viable for use in clinical practice for the detection of MS lesions in MRI.
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Francis, Simon J. "Automatic lesion identification in MRI of multiple sclerosis patients". Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82231.
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The object of this thesis is to describe tissue classification software that was developed specifically for the identification of cerebral white matter lesions found in patients with multiple sclerosis (MS). Multiple sclerosis is a debilitating disease of the central nervous system (CNS) which results in a pathology observable macroscopically by magnetic resonance imaging (MRI). Lesion volumes are used as a surrogate of disease progression in clinical trials for MS treatment. The availability of accurate, reliable and reproducible measurements is invaluable in the advancement of patient care and research into this disease. This thesis documents a comprehensive approach to achieve such results which to date has proven to be challenging. A novel fully automated Bayesian classifier was developed which utilizes a variety of techniques to more accurately model brain tissue, and performs lesion identification at a level comparable to human experts. A new validation model that affords a better estimation of ground truth is introduced, providing a better means to measure classification accuracy. It is hoped that this document will be practical in nature, so that people who continue this work will have a step upon which to start.
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Ingle, Gordon Thorpe. "Clinical and MRI features of primary progressive multiple sclerosis". Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444980/.
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In approximately 10-15% of cases Multiple Sclerosis follows a progressive rather than a relapsing course and this is known as Primary Progressive Multiple Sclerosis (PPMS). In this thesis previous clinical, pathological and Magnetic Resonance Imaging (MRI) studies of PPMS are reviewed and new studies using two cohorts of patients with PPMS are presented. In the first of these studies an existing cohort of patients with PPMS are re-examined at first two, and then five years, clinically and with MRI, to provide the longest period of MRI follow up in the condition to date. Changes in clinical and MRI measures over this time, and their correlation, are described. Over this extended period, some limited correlation can be found between clinical and MRI measures in PPMS. It is also seen that there is great variability in the rate of MRI and clinical progression between individuals with PPMS, although for a given individual progression is relatively constant. The possible implications of this observation for the nature of the underlying disease process are discussed. The second part of this thesis describes the clinical and MRI features of a second cohort of patients with clinically early PPMS, examined within five years of the first onset of symptoms, the first study to examine this stage of the condition. It is seen that much of the MRI variation seen in established PPMS is already present at this time and that the degree of MRI abnormality, even at this early stage, can be substantial. The specific question as to whether a distinct, early, inflammatory phase occurs in the condition (on the model of the more fully studied relapsing MS subtype) is addressed by the use of triple dose Gadolinium in a subgroup of this cohort examined over six months and evidence for the possible existence of such a phase in some patients with PPMS is found.
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Tench, Christopher. "Diffusion tensor MRI and its application to multiple sclerosis". Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289491.
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Thornton, Helena Barbara. "Cognition and multiple sclerosis: a neuropsychological and MRI study". Thesis, Rhodes University, 1996. http://hdl.handle.net/10962/d1007290.
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Ten people with multiple sclerosis (MS) who felt they had cognitive difficulties because of their MS were investigated. This study had multiple aims. Firstly, to explore the subjective experience of cognitive deficits. Secondly, to assess whether or not there was objective evidence of cognitive difficulties on neuropsychological testing, and whether this was commensurate with a pattern of subcortical dementia. Thirdly, to determine whether their magnetic resonance imaging (MRI) scans replicated the patterns of atrophy frequently reported in MS patients with cognitive difficulties. And finally, to investigate the psychological well-being of the subjects. In depth neuropsychiatric interviews, psychiatric and psychological inventories, a comprehensive neuropsychological battery, and MRI investigations were done. The mean Full Scale Intelligence Quotient (FSIQ) fell within the superior range, at the 89th percentile. On tests of general intelligence, mental state examinations, there was little or no indication of cognitive deterioration. However, on sophisticated neuropsychological testing, there was convincing evidence of cognitive problems. Magnetic resonance imaging lesions were atypical of the reported research on cognitively compromised MS patients.
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Samaraweera, Amal Prasanna Rohan. "MRI white matter lesion central veins in multiple sclerosis". Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/44840/.
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This thesis focuses on the use of the Magnetic Resonance Imaging (MRI) white matter lesion (WML) central vein as a biomarker for multiple sclerosis (MS). MS remains a clinical diagnosis, with reliance on MRI to support the diagnosis. Misinterpretation of the MRI can lead to misdiagnoses of diseases that mimic MS. With the increase in disease modifying treatments, accurate and timely diagnosis is needed now more than ever. Using T2* weighted imaging at 3 Tesla (T) MRI, I explored different aspects of WML central veins in patients with relapsing-remitting (RRMS), primary progressive MS (PPMS), and ischaemic small vessel disease (SVD) including: (1) the effect of using different T2* weighted sequences; (2) how T2* and susceptibility weighted imaging (SWI) and fused imaging techniques such as fluid attenuated inversion recovery (FLAIR)-SWI affected the proportion of WML central veins and; (3) determining if WML central veins were as prevalent in patients with PPMS. Further objectives included: (4) attempting to determine if vascular risk factors altered the proportion of WML central veins in patients with MS and; (5) using statistical modelling to calculate a simple diagnostic rule using WML central veins to differentiate MS from SVD. The proportion of WMLs with central veins differed significantly between patients with MS and SVD. Variations of the T2* sequence altered the proportion of WMLs with central veins, but the difference between MS and SVD remained statistically significant. T2* and SWI allowed a higher proportion of WMLs with central veins to be detected, with T2* being just as accurate as FLAIR-SWI in allowing the diagnosis of MS or SVD. Patients with PPMS and RRMS have a similarly high proportion of WMLs with central veins. High sensitivity and specificity for the diagnosis of MS versus SVD can be achieved by identifying a subset of WMLs with central veins. WML central veins could be used as an MRI biomarker using T2* imaging at 3T to differentiate cases of diagnostic uncertainty with RRMS, PPMS and SVD. Application of this imaging technique to patients with diagnostic uncertainty in prospective studies needs to be studied along with refining a clinical diagnostic rule.
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Dixon, Jennifer Elizabeth. "Optimisation of high-field MRI for investigation of multiple sclerosis". Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523042.
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Ghassemi, Rezwan. "MRI measures of brain injury in children with Multiple Sclerosis". Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123023.
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Multiple sclerosis (MS) is thought to be an autoimmune disease that affects the central nervous system of young adults. Although an uncommon disease in children, recent research has examined the effect of this disease upon a younger demographic group. This patient population has attracted the attention of MS researchers, as it promises a better understanding of the pathophysiology of MS at its earliest stage. Magnetic resonance imaging (MRI), a sensitive tool for detecting white matter (WM) pathology, has improved the diagnosis and appreciation of the pathogenesis of MS in adults. However, little is known about its use in children. Therefore, the main objective of this thesis is to contribute and to increase knowledge in this important new area. For this purpose, specific image processing methodologies were developed, and pathology on MRI was compared between patients with adult- and pediatric-onset MS. Comparing the spatial distribution, frequency, and volume of lesions on T2-weighted (T2w) MR images among patients with pediatric- and adult-onset MS, who had similar disease duration, showed a similar total T2w lesions between the two groups. However, children exhibited a higher T2w lesion volume and frequency in the infratentorial region, particularly in the pontine region. Persistent T1-weighted (T1w) lesions, a marker of permanent tissue damage and axonal loss, were assessed to determine whether MS lesions in children are as destructive as those in adults. To obtain a fair comparison using the scans available, normalization of intensity was essential. We showed the limitations of the currently available techniques for intensity normalization, and the need for a WM independent methodology. We proposed and developed a novel WM-independent intensity normalization method for T1w images and assessed inter-scanner, between-scanner and within subject variation before and after normalization. We also calculated the sample size required for detecting recovery of T1w intensity using our methodology and the most commonly used intensity normalization method. Then we used our methodology to assess recovery of normalized T1w intensity within new lesions in children with relapsing remitting MS (RRMS) compared to adults. We found that MS lesions recover better in children, suggesting a greater reparative capacity in younger patients. We also used our intensity normalization method to perform a quantitative comparison of T1w intensity recovery in new lesions between children with MS and children with monophasic inflammatory demyelinating syndromes (monoADS). We found that new MS lesions recover more poorly than of those in children with monoADS. This may suggest that new MS lesions are more destructive than new lesions in monophasic inflammatory demyelinating diseases.La sclérose en plaques (MS) est considérée comme une maladie auto-immune qui affecte le système nerveux central de l'adulte jeune. Bien que d'une maladie rare chez les enfants, des recherches récentes ont examiné l'effet de cette maladie sur une population plus jeune. Cette population de patients a attiré l'attention des chercheurs en SP, car elle promet une meilleure compréhension de la physiopathologie de la SEP au stade le plus précoce . Imagerie par résonance magnétique (IRM), un outil sensible pour la détection de la substance blanche (WM) pathologie, a amélioré le diagnostic et l'appréciation de la pathogenèse de la SEP chez les adultes. Cependant, peu a été connu au sujet de son utilisation chez les enfants. Par conséquent, l'objectif principal de cette thèse est de contribuer et d'accroître les connaissances dans ce nouveau domaine important. A cet effet, des méthodologies spécifiques de traitement d'image ont été développés, et de la pathologie à l'IRM ont été comparées entre les patients atteints de l'adulte et pédiatrique apparition MS. La comparaison de la répartition spatiale, la fréquence et le volume des lésions sur T2 (en T2) images IRM chez les patients atteints de la SP pédiatrique et adulte-début, qui ont eu la durée de la maladie similaire , ont montré un nombre total de lésions en T2 similaires entre les deux groupes. Cependant, les enfants présentaient un volume plus élevé de lésion en T2 et la fréquence dans la région infratentorial, en particulier dans la région pontique. (T1) des lésions pondérées en T1 persistants, un marqueur des dommages permanents aux tissus et la perte axonale, ont été évalués pour déterminer si les lésions de SP chez les enfants sont aussi destructrices que celles des adultes. Pour obtenir une comparaison équitable en utilisant les analyses disponibles, la normalisation de l'intensité était essentiel. Nous avons montré les limitations des techniques disponibles actuellement pour la normalisation de l'intensité, et le besoin d'une méthode indépendante WM. Nous avons proposé et développé une nouvelle méthode de normalisation de l'intensité WM- indépendante pour les images T1 et évalué inter- scanner, entre - scanner et dans l'objet variation avant et après normalisation. Nous avons également calculé la taille de l'échantillon nécessaire pour détecter la reprise de l'intensité T1w utilisant notre méthodologie et la méthode de normalisation de l'intensité la plus couramment utilisée. Ensuite, nous avons utilisé notre méthode pour tester notre hypothèse et la récupération assesed d'intensité T1w normalisée dans de nouvelles lésions chez les enfants sclérose en plaques rémittente (SEP-RR) par rapport aux adultes. Nous avons constaté que les lésions de SP mieux récupérer les enfants qui peuvent suggérer une plus grande capacité réparatrice chez les patients plus jeunes. Nous avons également utilisé notre méthode de normalisation de l'intensité pour effectuer une comparaison quantitative de la récupération de l'intensité T1w dans de nouvelles lésions entre enfants atteints de SP et les enfants atteints de syndromes inflammatoires démyélinisantes monophasiques (de monoADS). Nous avons constaté que de nouvelles lésions de SP récupérer plus mal que de ceux des enfants avec monoADS. Cela peut suggérer que les lésions New MS sont plus destructeur que de nouvelles lésions dans les maladies démyélinisantes inflammatoires monophasique.
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Edwards, Simon Graeme Mylrea. "MRI volumetric correlates of disease progression and activity in multiple sclerosis". Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407724.
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Taschler, Bernd. "Spatial point process models for MRI lesion data in multiple sclerosis". Thesis, University of Warwick, 2017. http://wrap.warwick.ac.uk/93636/.
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Over the past three decades neuroimaging techniques in general and magnetic resonance imaging (MRI) in particular have made large contributions to the understanding of human brain function and to the diagnosis and treatment of neurological diseases. One area of wide-spread clinical use of MRI is in the assessment of multiple sclerosis (MS). MS patients present with lesions – areas of decreased neuronal conductivity, akin scarred tissue – that occur across the brain and spinal cord. There has been growing interest to use quantitative measures of lesion incidence, exact lesion location and the shape of lesions in the analysis of MRI-based lesion data. Our objective is to address some of the limitations of current methods which rely on particular assumptions about the data and mostly ignore any spatial correlation and structure in the data. In this work we explore several ways of incorporating multiple sources of information into models that can be used for classification and prediction purposes. We compare and assess different machine learning and Bayesian spatial models in a classification task based on MS lesion data. Furthermore, we propose an extended doubly-stochastic spatial point process model based on Gamma random fields that includes non-imaging data as well as location-specific measures attached to xyz-coordinates, and use both simulated and real data to evaluate our methods.
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Nakamura, Kunio. "MRI Analysis to Detect Gray Matter Tissue Loss in Multiple Sclerosis". Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1309874290.
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Elsarraj, Afaf. "Advanced MRI techniques in studying multiple sclerosis pathology and lesion progression". Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/38612/.
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There is an intimate spatial and functional relationship between cerebral microvasculature and the neuroglial tissues. It is known that both cerebrovascular and neuroglial alterations occur in multiple sclerosis (MS), but the pathophysiological relationships between these alterations, and the functional consequences, are not well characterised in vivo. Evidence from previous literature indicates that there are subtle changes in blood brain barrier (BBB) in normal appearing white matter (NAWM) of MS. However, lesion development due to subtle BBB leakage remains unclear. Additionally, the haemodynamic alteration and microstructural changes in grey matter (GM) is a well-known feature in MS. Nevertheless, the structural and functional relevance of GM perfusion and diffusion necessitate more exploration. The main objective of this study was further interpretation of lesion development in MS, using advanced MRI techniques. Moreover, the study also aimed to provide valuable understandings into the association of different MRI measures with structural changes and clinical performance in MS, using advanced image analysis methods. The study has focused on the following goals: to determine BBB permeability in NAWM of MS and its correlation with microstructural damage, the relationship of subtle BBB leakage to lesion development, the association of grey matter perfusion with structural changes and functional performance and finally, the cortical diffusion alteration and its relevance with functional performance. Therefore, the main hypothesises of this thesis are: firstly, MS patients have impaired BBB permeability in NAWM compared to healthy controls. Secondly, that mean diffusivity (MD) in NAWM will correlate with BBB permeability in MS. Thirdly, that subtle BBB leakage in NAWM may precede lesion progression in MS. Fourthly, that cortical and deep GM perfusion is reduced in MS patients compared to healthy controls. Fifthly, that cortical perfusion correlates inversely with cortical atrophy in MS and finally, pattern of regional cortical MD variability will explain performance in different functional domains in MS. All MS and healthy participants included in this study underwent an MRI scan at 3T. Functional and cognitive assessment was performed on MS. Dynamic contrast enhance-MRI was used to generate perfusion and permeability maps. The microstructural changes were measured using diffusion imaging. The cortical perfusion and diffusion changes were explored by Surface based analysis approach. Increased BBB permeability in NAWM of MS was detected when compared to healthy controls (p<0.05) and it revealed an association with MD in NAWM (r= 0.48, p = 0.01). The findings also revealed subtle BBB breakdown indicated by an increase in the permeability parameter (Ktrans) in prelesion NAWM. GM hypoperfusion was shown in MS when compared to healthy controls (P<0.05). However, surface based analysis revealed no correlation between cortical hypoperfusion with cortical atrophy and microstructural damage in MS. Furthermore, there was no association between GM perfusion and clinical scores. In addition, the cortical diffusion alteration revealed vertex-wise correlation with functional scores in MS (P<0.05). In conclusion, advanced MRI and advanced image analysis in this study has delivered novel insights on lesion development and other pathological changes affecting GM and WM in MS, which might have prognostic and therapeutic importance in MS.
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Feng, Jenny J. "DEPRESSION IN MULTIPLE SCLEROSIS IS ASSOCIATED WITH WORSENING DISEASE-ANALYSIS OF A LARGE REAL WORLD COHORT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS". Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1607518627442055.
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Wu, Xingchen. "Multiple sclerosis : MRI diagnosis, potential treatment and future potential for nanoparticle applications /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-515-1/.
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ASLANI, SHAHAB. "Deep learning approaches for segmentation of multiple sclerosis lesions on brain MRI". Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/997626.
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Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system which causes lesions in brain tissues, especially visible in white matter with magnetic resonance imaging (MRI). The diagnosis of MS lesions, which is often performed visually with MRI, is an important task as it can help characterizing the progression of the disease and monitoring the efficacy of a candidate treatment. automatic detection and segmentation of MS lesions from MRI images offer the potential for a faster and more cost-effective performance which could also be immune to expert bias segmentation.
In this thesis, we study automated approaches to segment MS lesions from MRI images. The thesis begins with a review of the existing literature on MS lesion segmentation and discusses their general limitations. We then propose three novel approaches that rely on Convolutional Neural Networks (CNNs) to segment MS lesions.
The first approach demonstrates that the parameters of a CNN learned from natural images, transfer well to the tasks of MS lesion segmentation. In the second approach, we describe a novel multi-branch CNN architecture with end-to-end training that can take advantage of each MRI modalities individually. In that work, we also investigated the combination of MRI modalities leading to the best segmentation performance. In the third approach, we show an effective and novel generalization method for MS lesion segmentation when data are collected from multiple MRI scanning sites and as suffer from (site-)domain shifts. Finally, this thesis concludes with open questions that may benefit from future work. This thesis demonstrates the potential role of CNNs as a common methodological building block to address clinical problems in MS segmentation.
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Trowald, Adam. "A comparison between synthetic and conventional MRI". Thesis, KTH, Medicinsk teknik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-161645.
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This thesis describes the bene ts and disadvantages of using synthetic Magnetic Resonance Imaging (MRI) instead of conventional MRI. The thesis is based on a clinical study performed at Orebro University Hospital were 11 patients diagnosed with Multiple Sclerosis (MS) went through a brain examination with both methods. The examination time was measured and compared between the two methods, and the quality of the images was analysed by two radiologists. The study shows that the examination time can be reduced using the synthetic method instead of the conventional. The image quality is however not as good with the synthetic method which opens a discussion whether the time reduction is worth the loss of image quality. However, the conclusions are that the method can be useful for patients diagnosed with MS who are examined yearly and especially useful as a complement to the conventional sequence to gain as much information as possible that can be compared between the patients yearly exams. To completely replace other conventional examination types, the method has to be further evaluated and equipped with functions that are present in the conventional sequences, such as correction for motion artefacts.Denna rapport beskriver de fördelar och nackdelar som finns med att använda syntetisk magnetresonanstomografi (MRI) istället för konventionell MRI. Rapporten är baserad på en klinisk studie som har genomförts vid Universitetssjukhuset i Örebro där 11 patienter diagnostiserade med Multipel Skleros (MS) genomförde en undersökning av hjärnan med båda metoderna. Undersökningstiden mättes och jämfördes metoderna emellan, och bildkvaliteten analyserades av två radiologer. Den kliniska studien visar att undersökningstiden kan förkortas när den syntetiska metoden används i jämförelse med den konventionella. Bildkvaliteten för de konventionella bilderna anses vara av högre kvalitet i denna studie vilket öppnar en diskussion gällande huruvida det är värt att förlora en viss bildkvalitet mot förkortat undersökningstid. Slutsatsen är att metoden är användbar för patienter diagnostiserade med MS som undersöks årligen, och speciellt användbar som ett komplement till de konventionella sekvenserna för att generera så mycket information som möjligt. Denna information är sedan användbar vid jämförelse av bilderna från patienternas återkommande undersökningar. För att helt ersätta de konventionella sekvenserna krävs vidare utvärderings av den syntetiska metoden samt att den kompletteras med er funktioner, exempelvis för att korrigera för rörelseartefakter.
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García-Lorenzo, Daniel. "Robust Segmentation of Focal Lesions on Multi-Sequence MRI in Multiple Sclerosis". Phd thesis, Université Rennes 1, 2010. http://tel.archives-ouvertes.fr/tel-00485645.
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La sclérose en plaques (SEP) atteint autour de 80.000 personnes en France. L'imagerie par résonance magnétique (IRM) est un outil essentiel pour le diagnostic de la SEP. Plusieurs bio-marqueurs sont obtenus à partir des IRM, comme le volume des lésions, et sont utilisés comme mesure dans des études cliniques en SEP, notamment pour le développement des nouveaux traitements. La segmentation manuelle des lésions est une tâche encombrante et dont les variabilités intra- et inter-expert sont grandes. Nous avons développé une chaîne de traitement automatique pour la segmentation des lesions focales en SEP. La méthode de segmentation est basée sur l'estimation robuste d'un modèle paramétrique des intensités du cerveau qui permet de détecter les lésions comme des données aberrantes. Nous avons aussi proposé deux méthodes pour ajouter de l'information spatiale avec les algorithmes mean shift et graph cut. Nous avons validé quantitativement notre approche en utilisant des images synthétiques et cliniques, provenant de deux centres différents pour évaluer la précision et la robustesse.
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García, Lorenzo Daniel. "Robust segmentation of focal lesions on multi-sequence MRI in multiple sclerosis". Rennes 1, 2010. http://www.theses.fr/2010REN1S018.
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La sclérose en plaques (SEP) atteint autour de 80. 000 personnes en France. L'imagerie par résonance magnétique (IRM) est un outil essentiel pour le diagnostic de la SEP. Plusieurs bio-marqueurs sont obtenus à partir des IRM, comme le volume des lésions, et sont utilisés comme mesure dans des études cliniques en SEP, notamment pour le développement des nouveaux traitements. La segmentation manuelle des lésions est une tâche encombrante et dont les variabilités intra- et inter-expert sont grandes. Nous avons développé une chaîne de traitement automatique pour la segmentation des lesions focales en SEP. La méthode de segmentation est basée sur l'estimation robuste d'un modèle paramétrique des intensités du cerveau qui permet de détecter les lésions comme des données aberrantes. Nous avons aussi proposé deux méthodes pour ajouter de l'information spatiale avec les algorithmes mean shift et graph cut. Nous avons validé quantitativement notre approche en utilisant des images synthétiques et cliniques, provenant de deux centres différents pour évaluer la précision et la robustesseMultiple sclerosis (MS) affects around 80. 000 people in France. Magnetic resonance imaging (MRI) is an essential tool for diagnosis of MS and MRI-derived surrogate markers such as MS lesion volumes are often used as measures in MS clinical trials for the development of new treatments. The manual segmentation of these MS lesions is a time-consuming task that shows high inter- and intra-rater variability. We developed an automatic workflow for the segmentation of focal MS lesions on MRI. The segmentation method is based on the robust estimation of a parametric model of the intensities of the brain; lesions are detected as outliers to the model. We proposed two methods to include spatial information in the segmentation using mean shift and graph cut. We performed a quantitative evaluation of our workflow using synthetic and clinical images of two different centers to verify its accuracy and robustness
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Poggiali, Davide. "Postprocessing Neuroimaging methods in MRI and PET/MRI with applications to Multiple Sclerosis and other Neurological diseases". Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3421919.
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Many non-invasive imaging instruments have been developed in the last 40 years, allowing to obtain images of the interior human body while the patient is still alive. In the contest of Neurology studies, imaging system as CT, MRI, SPECT or PET allows to obtain biomarkers useful to quantitatively distinguish between healthy and unhealthy subjects, evaluate the staging of a Neurological illness in a patient, evaluate the efficacy of a treatment, explore the causes of the illness.
In this work MRI and PET imaging system introduced from scratch, going from reconstruction from raw data to state-of-the art post-processing techniques and the computation of more popular biomarkers.
After these introduction, three original work using the recent PET/MRI imaging system are presented, with a particular focus on the methods. These three studies involve patients with Multiple Sclerosis, Alzheimer's Disease and Brain Tumor.Negli ultimi 40 anni sono stati sviluppati diversi strumenti di imaging non-invasivi, in modo da ottenere immagini dell'interno del corpo umano mentre il paziente è ancora in vita. Nel contesto neurologico, sistemi di imaging come TAC, RM, SPECT e PET permettono di ottenere biomarcatori utili a distinguere quantitativamente soggetti sani da pazienti con malattie neurologiche, valutare lo stato di avanzamento di una malattia in un paziente, valutare l'efficacia di un trattamento, esplorare le cause della malattia. Nel presente lavoro si presentano i sistemi di acquisione di immagini RM e PET fin dalle fondamenta, partendo dai metodi di ricostruzione dell'immagine dai dati grezzi, allo stato dell'arte dei metodi di post-processing, fino al calcolo dei biomarcatori più diffusi. Dopo tale introduzione saranno presentati tre lavori originali di imaging PET/MRI, con una particolare attenzione ai metodi. Questi tre lavori riguardano pazienti con Sclerosi Multipla, Morbo di Alzheimer e Tumori Cerebrali.
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Lysandropoulos, Andreas. "HLA genotype as a marker of Multiple Sclerosis prognosis". Doctoral thesis, Universite Libre de Bruxelles, 2020. https://dipot.ulb.ac.be/dspace/bitstream/2013/312863/4/Thesis.pdf.
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This thesis aimed to establish how different HLA genotypes correlate to MS severity and disease progression and whether they could be used as additional disease biomarkers and to a large extent the work has succeeded in this task. Association of MS with the alleles HLA-DRB1*15 and HLA-DQB1*06 and haplotype DRB1*15-DQB1*06 was identified, and under representation of other alleles, such as the HLA-DRB1*07 and HLA-A*02 alleles, showed a potentially protective role against the disease. HLA-A*02 was shown to be a marker of a better prognosis and, in contrast, HLA-B*07, B*08 and B*44 seem to be associated to with a worse prognosis.Doctorat en Sciences médicales (Médecine)
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Sheikhzadeh, Fahime. "Mathematical modelling of the spatial dispersion of brain MRI lesions in multiple sclerosis". Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/42225.
Texto completoResumen
Many previous studies in multiple sclerosis (MS) have focused on the relationship between white matter lesion volume and clinical parameters, but few have investigated the independent contribution of the spatial dispersion of lesions to patient disability.
In this thesis, we investigate whether a mathematical measure of the 3D spatial dispersion of lesions can reveal clinical significance that is independent of volume. Our hypothesis is that for any two given patients with similar lesion loads, the one with greater lesion dispersion would tend to have a greater disability. We investigate four different approaches for quantifying lesion dispersion and examine the ability of these lesion dispersion measures to act as potential surrogate markers of disability. We propose one connectedness-based measure (compactness), two region-based measures (ratio of minimum bounding spheres and ratio of lesion convex hull to the brain volume), two distance-based measures (Euclidean distance from a fixed point and pair-wise Euclidean distances) and one measure based on network theory (small-worldness). Our data include three sets of MRIs (n = 24, 174, 182) selected from two MS clinical trials. We segment all white matter lesions in each scan with a semi-automatic method to produce binary images of lesion voxels, quantify their spatial dispersion using the defined measures, then perform a statistical analysis to compare the dispersion values to total lesion volume and patient disability. We use linear and rank correlations to investigate the relationships between dispersion, disability, and total lesion volume, and regression analysis to investigate whether there is a potentially meaningful relationship between dispersion and disability, independent of volume. Our main finding is that one distance based measure, Euclidean distance from a fixed point, consistently correlates with disability score across all three datasets, and has predictive value that is at least partly independent of lesion volume. The results provide support for our hypothesis and suggest that a potentially meaningful relationship exists between patient disability and measurements of lesion dispersion. Finding such relationships can improve the understanding of MS and potentially lead to the discovery of novel surrogate biomarkers for clinical use in designing treatment trials and providing prognostic advice to individual patients.
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Veronese, Elisa. "Methods for segmentation and characterization of multiple sclerosis cortical lesions from MRI data". Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422439.
Texto completoResumen
This thesis deals with the automatic analysis of magnetic resonance images of the brain, acquired from people affected by multiple sclerosis. In particular, the primary aim of the analysis is to obtain a quantitative measure of the cortical lesion burden due to the specific disease. Besides, we propose a technique for the characterization of the different lesion types, based on their inflammatory activity.
Multiple sclerosis is a chronic, inflammatory disease of the central nervous system, that causes a progressive demyelination of several areas of the brain and of the spinal cord. As far as diseases’ frequency is concerned, multiple
sclerosis represents the second neurologic disease in the young adult, and it is even the first inflammatory chronic disease. Besides, it can also be considered as a social burden, with heavy direct and indirect costs: multiple sclerosis prevents people from working as much as they could without the disease, and can lead to the impossibility to live autonomously. Last but not least, the cost of treatment and care can be very high.
Although the causes are still partly unclear, a lot has been achieved in the understanding of the different phases of the inflammatory process characterizing multiple sclerosis. Today it is possible to early diagnose the disease, thus allowing to limit symptoms by early therapies.
The lesions caused by multiple sclerosis can be visualized in vivo thanks to magnetic resonance (MR) imaging. In particular in the latest decades several MR sequences have been designed in order to highlight white matter lesions.
When studying gray matter lesions, instead, the available MR sequences are less numerous. This is partly due to the fact that the gray matter involvement in multiple sclerosis is a relatively recent finding.
It is important to verify both the evolution and the appearance of new lesions: in this way it is possible to monitor the disease progression, which is particularly tricky in the case of multiple sclerosis. This disease is characterized by acute relapses alternated with remitting periods of variable length.
For this reason patients are periodically examined acquiring MR images. The subsequent diagnosis made by the physician is based on the MR results.
So, it is fundamental for the neurologist to be well trained in order to be able to properly evaluate different magnetic resonance sequences. Besides, he/she has to pay close attention not only to detect new lesions, but also to recognize
those lesions that were already present in the previous examinations, and that might have changed their shape, their dimension or they activity. This process requires time and attention, but unfortunately, being human-based, it is strongly error prone. Unquestionably, the diagnose cannot prescind from
the neurologist’s evaluation. Nonetheless, the advent of techniques for the automatic analysis of magnetic resonance images and for the detection of multiple sclerosis lesions would represent a valid support for the physicians, who could provide accurate evaluations in faster timing.
In this thesis several MR techniques currently used for cortical lesions visualization will be described. Then a segmentation algorithm will be proposed, in order to find the region corresponding to gray matter. On this region a second algorithm will be presented, that detect multiple sclerosis cortical lesions.
Finally, a first attempt to characterize cortical lesions based on their inflammatory activity will be described.Questa tesi tratta l’analisi automatica di immagini di risonanza magnetica cerebrale in soggetti affetti da sclerosi multipla. In particolare, l’analisi è volta sia a una stima quantitativa del carico di lesioni corticali presenti a causa del decorso della malattia, sia a una caratterizzazione del tipo di lesioni presenti basata sul loro grado di infiammazione. La sclerosi multipla è una malattia infiammatoria a decorso cronico che colpisce il sistema nervoso centrale, provocandone una progressiva distruzione della mielina in più aree. Per frequenza, nel giovane adulto è la seconda malattia neurologica e la prima di tipo infiammatorio cronico. Inoltre, la sclerosi multipla può essere considerata anche come malattia sociale, con un’elevata ricaduta economica, sia diretta che indiretta: la diminuzione o la perdita dell’autonomia porta alla progressiva impossibilità di svolgere una qualsiasi attività lavorativa fino all’incapacità di condurre una vita indipendente. A questo si aggiungano il costo delle cure e dell’assistenza necessarie. Benché le cause siano ancora in parte sconosciute, molto è stato fatto nel chiarire le diverse fasi del processo infiammatorio che caratterizza tale patologia, permettendo così di arrivare a una diagnosi e a un trattamento precoce che consentono di ridurre gli effetti della malattia. Le lesioni causate dalla sclerosi multipla risultano visibili grazie a particolari tecniche di acquisizione di immagini basate sulla risonanza magnetica. In particolare negli ultimi decenni si sono studiate e messe a punto diverse sequenze di risonanza ottimizzate per la visualizzazione delle lesioni in materia bianca. Il quadro delle tecniche a disposizione qualora si vogliano studiare lesioni in materia grigia risulta invece meno completo, soprattutto a causa del fatto che la scoperta di un coinvolgimento della materia grigia nella malattia è molto più recente. La verifica dell’evoluzione e della comparsa di nuove lesioni è importante dal momento che consente di monitorare il progredire di una malattia caratterizzata da fasi acute intervallate a periodi di quiescenza più o meno lunghi. Per questo motivo i soggetti affetti da sclerosi multipla vengono periodicamente sottoposti a esami di risonanza magnetica. Ogni successiva valutazione da parte del medico neurologo dipenderà da quanto evidenziato dalle immagini acquisite. In questo senso è fondamentale che il medico sia ben allenato nella valutazione di immagini di risonanza, e che ponga particolare attenzione non solo nell’individuare la comparsa di nuove lesioni, ma anche nel riconoscere la presenza di lesioni già presenti in esami precedenti, che possono essere progredite nella forma, nelle dimensioni e nel grado di attività. La lettura di un esame di risonanza magnetica richiede tempo e attenzione, ed è inevitabilmente soggetta all’errore umano che caratterizza qualsiasi valutazione manuale. Per questo, benché sia impensabile prescindere dalla valutazione del medico, una tecnica di analisi automatica di immagini di risonanza magnetica cerebrale che sia in grado di evidenziare la presenza di lesioni da sclerosi multipla può rappresentare un valido aiuto alla refertazione, sia in termini di tempo che di accuratezza. In questa tesi si descriveranno le tecniche di risonanza magnetica a disposizione per una miglior visualizzazione delle lesioni corticali. Su queste si procederà alla segmentazione del tessuto di interesse, ossia del volume di materia grigia. In seguito verrà descritta la tecnica proposta per il riconoscimento delle regioni patologiche corticali. Infine sarà descritto un primo tentativo di caratterizzazione delle diverse lesioni corticali, basato sulla valutazione del grado di attività di ciascuna lesione.
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Weatherby, Stuart J. M. "Visual, magnetic resonance, and genetic studies of outcome in multiple sclerosis". Thesis, Keele University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368980.
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Li, Xiaobai. "Stochastic models for MRI lesion count sequences from patients with relapsing remitting multiple sclerosis". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1142907194.
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González, Ballester Miguel Ángel. "Morphometric analysis of brain structures in MRI". Thesis, University of Oxford, 1999. http://ora.ox.ac.uk/objects/uuid:9b70d5d7-5a38-454c-b545-696b726092b8.
Texto completoResumen
Medical computer vision is a novel research discipline based on the application of computer vision methods to data sets acquired via medical imaging techniques. This work focuses on magnetic resonance imaging (MRI) data sets, particularly in studies of schizophrenia and multiple sclerosis. Research on these diseases is challenged by the lack of appropriate morphometric tools to accurately quantify lesion growth, assess the effectiveness of a drug treatment, or investigate anatomical information believed to be evidence of schizophrenia. Thus, most hypotheses involving these conditions remain unproven. This thesis contributes towards the development of such morphometric techniques. A framework combining several tools is established, allowing for compensation of bias fields, boundary detection by modelling partial volume effects (PVE), and a combined statistical and geometrical segmentation method. Most importantly, it also allows for the computation of confidence bounds in the location of the object being segmented by bounding PVE voxels. Bounds obtained in such fashion encompass a significant percentage of the volume of the object (typically 20-60%). A statistical model of the intensities contained in PVE voxels is used to provide insight into the contents of PVE voxels and further narrow confidence bounds. This not only permits a reduction by an order of magnitude in the width of the confidence intervals, but also establishes a statistical mechanism to obtain probability distributions on shape descriptors (e.g. volume), instead of just a raw magnitude or a set of confidence bounds. A challenging clinical study is performed using these tools: to investigate differences in asymmetry of the temporal horns in schizophrenia. This study is of high clinical relevance. The results show that our tools are sufficiently accurate for studies of this kind, thus providing clinicians, for the first time, with the means to corroborate unproven hypotheses or reliably assess patient evolution.
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Bami, Cole Orlean Isaiah. "Identification/extraction of Multiple Sclerosis lesions in multi-channel MRI data using pattern analysis". Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285685.
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Furby, J. "Investigation of neurodegeneration and neuroprotection in secondary progressive multiple sclerosis using volumetric MRI measures". Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/20452/.
Texto completoResumen
Multiple sclerosis (MS) is a disabling neurological disorder that affects young people. Neuroaxonal loss is believed to be the pathological correlate of the secondary progressive phase of this disease and whilst the earlier, relapsing disease is responsive to immunomodulatory treatments, progressive disease has proved resistant. Clinical trials in progressive multiple sclerosis are problematic due the variable nature of disability progression and the insensitivity of currently available disability scales. Volumetric magnetic resonance imaging (MRI) measures of brain and spinal cord atrophy are pathologically non-specific but are likely to reflect destructive processes such as neuroaxonal loss and could be used to assess treatment efficacy in clinical trials of neuroprotective agents in MS. Presented, is work assessing MRI-based atrophy measurements of various regions within the central neuroaxis in secondary progressive MS, in particular assessing their attributes for use as surrogate markers. The clinical and MRI data were acquired as part of a phase II trial of a putative neuroprotective agent, lamotrigine, in subjects with secondary progressive MS, and the treatment effect of this agent on the volumetric MRI measures is also presented. Overall measures of whole brain, grey matter and spinal cord atrophy demonstrated robust correlations with disability, both in cross-sectional and longitudinal analyses. Grey matter and spinal cord volumes were subject to high rates of change. In contrast white matter atrophy was variable and on average did not change significantly over the 2 year follow-up. Of interest was that grey matter volume was highly correlated with T1 hypointense lesion load in the white matter suggesting a possible causative link. No significant beneficial treatment effect of lamotrigine was demonstrated using any of the MRI measures. However, an early “pseudoatrophy” was observed within the white matter compartment in the treatment group suggesting an anti-inflammatory or osmotic effect.
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Kearney, H. "Investigation of multiple sclerosis spinal cord using high field MRI with multi-transmit technology". Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1452991/.
Texto completoResumen
This thesis explores abnormalities in the multiple sclerosis (MS) spinal cord and their relationship with physical disability through the use of conventional and quantitative magnetic resonance imaging (MRI). Firstly, an hypothesis was tested that spinal cord atrophy would be associated with disability, independently from brain atrophy and lesion load, in long disease duration MS. The results presented confirm that cord atrophy is significantly associated with higher levels of physical disability after more than twenty years of MS. Following this observation, the next experiment investigated whether a combination of an active surface model (ASM) and high resolution axial images, would provide a more reproducible measure of spinal cord cross-sectional area; compared to previously described methodologies. The results presented show the superior reproducibility of the ASM combined with axial images for the measurement of cord area in MS, which may be of relevance to future clinical trials utilising cord atrophy as an outcome measure. The pathology of MS in the spinal cord was also explored in several ways using MRI. Firstly, spinal cord lesion morphology was studied, to investigate whether focal lesions, that traversed two or more spinal cord columns and involved the grey matter, would be associated with progressive MS. The results presented confirm this association and also that diffuse abnormalities are more frequently seen in progressive disease. Secondly, spinal cord lesion load was measured quantitatively on axial images, to investigate if this measure would be associated with disability independently from cord atrophy. The functional importance of focal lesions in MS is highlighted by demonstrating an independent association between lesion load and disability. Thirdly, magnetisation transfer ratio (MTR) measures of the outer spinal cord were obtained, in an area expected to contain the pia mater and subpial tissue, to investigate whether outer cord abnormalities could be seen in MS compared to healthy controls and if such abnormalities would be associated with cord atrophy. The results presented show that significant decreases in MTR occur in the outer cord early in the disease course, prior to the development of cord atrophy and further decreases in MTR were seen in progressive MS. Furthermore, an independent association is presented between outer cord MTR and cord atrophy, suggesting that spinal cord meningeal inflammation may be associated with axonal loss in MS. Lastly, diffusion tensor imaging was used in the spinal cord grey matter, in order to investigate whether microstructural abnormalities in this structure would be associated with physical disability. The results of this study identified an association between grey matter radial diffusivity and disability, independently from cord atrophy, suggesting a significant contribution of spinal cord grey matter pathology to clinical dysfunction. In summary, this thesis shows that MS spinal cord abnormalities may be visualised and quantified using high field MRI, and are significantly associated with disability. The observations presented may of relevance to future MRI studies and clinical trials in MS that aim to understand and potentially prevent the pathological processes underlying irreversible physical disability.
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Snoussi, Haykel. "Population imaging and diffusion MRI for characterizing multiple sclerosis in the human spinal cord". Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1S022/document.
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L'IRM quantitative a un potentiel énorme pour fournir une valeur intrinsèque et indirecte aux propriétés des tissus utiles au diagnostic, au pronostic et aux essais cliniques de la sclérose en plaques (SEP), qui est une maladie inflammatoire du système nerveux central. Complémentaire à l’imagerie cérébrale, étudier l’impact de la maladie sur la moelle épinière grâce à l’imagerie quantitative, en particulier l’IRM de diffusion, devient un véritable défi. L'acquisition et le traitement de ce type de données posent des problèmes inhérents en raison de la distorsion de susceptibilité, de la petite section transversale de la moelle et l’absence de repères anatomiques visibles qui permettant d'identifier des voies ou du niveau vertébral. Dans ce contexte, nous proposons plusieurs contributions pour le traitement et l'analyse statistique de ces données. Tout d'abord, nous proposons de nouvelles métriques géométriques pour évaluer et comparer différentes méthodes de correction de distorsion en mesurant l'alignement du modèle de diffusion reconstruit avec l'axe central apparent de la moelle épinière. Deuxièmement, en utilisant une cohorte de patients atteints de SEP et de témoins sains, nous étudions le lien entre les mesures de diffusion et la présence ou l'absence de lésion dans un niveau vertébral donné et nous montrons que nous pouvons prédire ce dernier avec une bonne précision en utilisant un apprentissage linéaire multivarié. Enfin, nous montrons la faisabilité d’une étude longitudinale de l’évolution des métriques d'IRM de diffusion en réalisant une étude de reproductibilité à l’aide d’un ensemble de données test-retest, et l’appliquons aux 2 premières acquisitions (M0 et M12) de notre cohorte de patientsQuantitative MRI has huge potential to provide intrinsic and normative value to tissue properties useful for diagnosis, prognosis and ultimately clinical trials in multiple sclerosis (MS) which is an inflammatory disorder of the central nervous system. Complementary to brain imaging, investigating how the spinal cord is damaged using quantitative imaging, and in particular diffusion MRI, becomes an acute challenge. Acquiring and processing this type of data present inherent challenges due to the susceptibility distortion, the small crosssectional area of the spine and the lack of visible anatomical landmarks to help identification of tracts or vertebral level. In this context, we propose several contributions for the processing and statistical analysis of this data. First, we propose novel geometric metrics to evaluate and compare different distortion correction methods by measuring the alignment of the reconstructed diffusion model with the apparent centerline of the spine. Second, using a cohort of MS patients and healthy controls, we study the link between diffusion measures and the presence or absence of lesion in a given vertebral level and we show that we can predict the latter with good accuracy by learning a multivariate linear classifier. Last, we show the feasibility of longitudinal study of the evolution of diffusion MRI metrics by performing a reproducibility study using a test-retest dataset and apply it to the 2 first timepoints (M0 and M12) of our cohort of MS patients
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CAMMAROTO, VIVIANA. "Functional and Morphological Correlates of Cognitive and Social Cognition Impairment in Multiple Sclerosis. A Longitudinal Study". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2018. http://hdl.handle.net/10281/241347.
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La sclerosi multipla (SM) è il prototipo delle malattie demielinizzanti, in cui la patologia della sostanza grigia e bianca (GM/WM) contribuisce alla compromissione di diversi domini cognitivi tra cui l’attenzione, la velocità di elaborazione mentale, la memoria, le funzioni esecutive e visuospaziali, così come molti aspetti della cognizione sociale.
L’obiettivo principale del presente studio di risonanza magnetica (MRI) era di indagare l’effetto della SM sulla cognizione e sulla struttura del cervello, combinando indagini neuropsicologiche e morfologiche. Abbiamo mirato ad analizzare i cambiamenti delle principali funzioni cognitive nel tempo in pazienti ambulatoriali con SM recidivante-remittente (SMRR) lieve e iniziale rispetto ai soggetti sani, e correlato questi risultati ai cambiamenti di volume regionale nella GM. Abbiamo inoltre esplorato l’impatto della SM su molti aspetti della cognizione sociale, dell’umore, della fatica, del benessere psicologico e della qualità della vita di questi pazienti tra l’inizio e la fine dello studio.
Il primo risultato MRI importante riguardava l’identificazione di un pattern di atrofia temporale destra (giro temporale inferiore e polo temporale medio) nel gruppo SMRR rispetto ai controlli normali, che è rimasto invariato tra la valutazione basale e il follow-up. Dopo un anno, è emersa una considerevole atrofia della GM profonda dell’emisfero destro (amigdala, globo pallido e putamen) e del cervelletto (14.2%), mentre scompariva nel putamen e nell’insula dell’emisfero sinistro. Inoltre, fattori quali il sesso, l’età e la velocità di elaborazione (cioè, il Symbol Digit Modalities Test) erano in grado di predire il volume della GM dei pazienti a un anno.
Per quanto riguarda la valutazione cognitiva, i risultati primari evidenziavano che una grande percentuale (circa il 50%) del gruppo SMRR era significativamente compromessa rispetto ai controlli in prove riguardanti memoria a breve ed a lungo termine, velocità di elaborazione, funzioni visuospaziali ed esecutive, ed emozioni negative (tristezza e rabbia). I pazienti mostravano inoltre sintomi di disagio psicologico (somatizzazione, ossessività-compulsività, ostilità e problemi interpersonali). Queste difficoltà tendevano ad appiattirsi nel tempo nel gruppo SMRR. Mentre la memoria a lungo termine, le abilità visive percettive e spaziali e l’attribuzione della rabbia sembravano migliorare, i deficit di memoria di lavoro, velocità di elaborazione e inibizione dell’interferenza, e il riconoscimento della tristezza rimanevano stabili dopo un anno. Al follow-up, anche le caratteristiche di disagio psicologico si erano attenuate, ma emergevano nuovi sintomi depressivi.
In conclusione, i nostri risultati hanno evidenziato che vi era un declino cognitivo minimo ma significativo nel gruppo SMRR. Il pattern di atrofia temporale riscontrato nei pazienti rispetto ai controlli poteva rendere conto dei loro deficit iniziali. Dopo un anno, la significativa riduzione dei volumi cerebellari e delle strutture GM profonde poteva inoltre spiegare perché le difficoltà primarie nella memoria e nel riconoscimento della tristezza erano rimaste stabili, mentre le altre erano diminuite. Tutti questi deficit non erano significativamente correlati ad altri fattori, come l’umore, la fatica e le caratteristiche cliniche della malattia. Sebbene le prestazioni in alcune misure esecutive siano probabilmente migliorate a causa dell’effetto della pratica, al follow-up di un anno la memoria di lavoro e la velocità di elaborazione erano ancora compromesse, dimostrando che la progressione a breve termine della malattia ha un impatto clinicamente significativo su queste capacità. Anche gli aspetti emozionali e comportamentali erano migliorati nel tempo, suggerendo che la gestione sanitaria precoce e il trattamento farmacologico possono contribuire al benessere e alla qualità della vita delle persone con SM.Multiple sclerosis (MS) is the prototype of demyelinating diseases, in which both gray and white matter (GM/WM) pathology contribute to impairment of several cognitive domains including attention, mental processing speed, memory, executive and visuospatial functions, as well as many aspects of social cognition. Such deficits have been reported in all stages and subtypes of the disease, and result in significant, negative consequences for mood and quality of life of people with MS. The main goal of the current magnetic resonance imaging (MRI) study was to investigate the effect of MS on cognition and brain structure, by combining neuropsychological and morphological investigations. More precisely, we aimed to analyze changes of main cognitive functions over time in mild and early relapsing-remitting MS (RRMS) outpatients compared to healthy subjects, and correlated these findings to GM regional volume changes. We were also interested to explore the impact of MS on many aspects of social cognition, mood, fatigue, psychological well-being, and quality of life of these patients between the beginning and the end of the study. The first important MRI result was the identification of a right temporal atrophy pattern (inferior temporal gyrus and middle temporal pole) in the RRMS group compared to normal controls, which was unchanged between the baseline and follow-up. After one year, a considerable atrophy in deep GM of right hemisphere (amygdala, globus pallidus and putamen) and cerebellum (14.2%) emerged, while disappeared in the left putamen and insula. In addition, the GM volume of the patients at one year was predicted by sex, age, and processing speed (i.e., Symbol Digit Modalities Test). As for the cognitive evaluation, primary results highlighted that a large proportion (about 50%) of the RRMS group was significantly impaired compared with controls on short- and long-term memory, processing speed, visuospatial and executive functions, and negative emotions (sadness and anger). Patients also showed symptoms of psychological distress (somatization, obsessive-compulsiveness, hostility, and interpersonal problems). These impairments in the RRMS group tended to flatten over time. While long-term memory, perceptual and spatial visual skills, and the anger attribution seemed to improve; deficits in working memory, processing speed and interference inhibition, and the recognition of sadness remained stable after one year. At the follow-up, characteristics of psychological distress were also reduced, but new depressive symptoms emerged. In conclusion, our results highlighted that there was a minimal but significant cognitive impairment in the RRMS group. After one year, a significant reduction in the cerebellar and deep GM structure volumes could also explain why primary deficits in memory and recognition of sadness remained stable, while the others decreased. All these impairments were not significantly related to other factors, such as mood, fatigue and clinical features of the disease. Although performance in some executive measures probably improved due to ‘practice effect’, working memory and processing speed were still impaired at one-year follow-up, proving that the short-term progression of the disease has a clinically meaningful impact on these abilities. Even emotional-behavioral aspects had improved over time, leading to a better adaptation to the disease by patients. Early management of healthcare taking-charge and pharmacological treatment, which occur at the initial stage of the disease, may also contribute to the well-being and quality of life of people with MS.
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Vignos, Megan C. "A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT". Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461528682.
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Zheng, Yufan. "Serial MRI Analysis to Track Long-term Evolution of White Matter Lesions in Multiple Sclerosis". Cleveland State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=csu1495211969857372.
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Herbert, Estelle Penelope. "Magnetic Resonance Imaging and Biochemical markers to assess disability in female subjects with Multiple Sclerosis". Thesis, Cape Peninsula University of Technology, 2016. http://hdl.handle.net/20.500.11838/2404.
Texto completoResumen
Thesis (M.Sc (Radiography))--Cape Peninsula University of Technology, 2016.Multiple sclerosis (MS) affects the central nervous system (CNS) and is characterized by multiple demyelinating lesions. It is in this context that a need arises for reliable biomarkers such as Magnetic Resonance Imaging (MRI), which could lead to the early diagnosis and therapeutic intervention when maximum potential impact is possible. This study examines the impact of MRI as a marker and the sequences that give the best images to aid in evaluation of disease progression (which can indirectly be seen as disability) and the early diagnosis of MS which will, in turn, lead to more effective management of the disease. METHOD: Sixteen subjects underwent a neurological examination, the Expanded Disability Status Scale (EDSS), blood tests for iron parameters and a 3Tesla Magnetic Resonance Imaging (MRI) scan. In a study of MS, 11 had MRI data that could be analysed by using tract-based spatial statistics (TBSS). Subjects were divided according to the EDSS score (8 of the subjects had an EDSS score of ≤ 3 while 3 subjects had scores of ≥ 6). Diffusion tensor imaging (DTI), the fused Proton Density and Fluid Attenuation Recovery (FLAIR) was utilised to compute the lesion numbers and standard laboratory procedures were used to measure other biochemical markers (serum iron, % transferrin saturation, ferritin, haemoglobin) in subjects with disability and simultaneously assess the disease process. RESULTS: The FA of white matter tracts (WMTs) as a parameter of myelin integrity was lower in subjects with MS only in those who had high EDSS scores. An association between FA and iron parameters, especially percentage transferrin saturation (% Tf) sat were observed, which suggests that iron availability to the WM may be a requirement for optimal myelin functionality. CONCLUSION: The FA of WMTs as a parameter of myelin integrity was lower only in those MS subjects who had high EDSS scores. Subjects who had EDSS scores < 3 (i.e. who had a “benign” disease outcome) had FA values similar to control values and this finding was not related to their age or disease duration. The association found between FA and iron parameters, especially % Tf sat, suggests that iron availability to the WM may be a requirement for optimal myelin functionality. Results also suggest that serum iron concentration, ferritin and % Tf sat had an effect on myelination. The lack of association between FA and Hb suggests that the iron in this protein is not available for WM function.
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Chen, Jacqueline T. 1973. "Image-processing of MRI for measuring brain injury, repair and degeneration in patients with multiple sclerosis". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=113848.
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This thesis presents methods for quantitative MRI analysis of brain injury, repair and degeneration in multiple sclerosis (MS) that provide new insights into disease pathogenesis and evolution.Demyelinated and inflammatory white-matter lesions are hallmark features of MS. A methodology is described to detect regions of acute white-matter lesions that undergo myelin destruction and repair based on analysis of magnetization transfer ratio (MTR) images. Validation is performed based on histopathology and error is assessed based on same-day scans. To quantify the spatial extent and temporal evolution of myelin destruction and repair, data from a 3-year clinical trial is analyzed using this method. Approximately 20% of acute lesion voxels show some repair over the initial 7 months. In subsequent months, there is little further repair, but some increases in the lesion volume undergoing demyelination.
Although less conspicuous on conventional MRI, there is considerable MS pathology in the brain tissue outside of white-matter lesions. An image-processing methodology was developed to obtain accurate metrics that quantify change over time in whole-brain MTR (associated with changes in myelin-density) and in T2 relaxation time (associated with changes in inflammatory edema). These metrics, in addition to metrics of brain atrophy and axonal integrity, were used to quantify brain injury and degeneration following immunoablation and autologous hematopoietic stem cell transplantation therapy for MS. Pronounced brain volume loss was detected immediately following therapy, associated with decreased myelin density and not resolution of edema.
Post-mortem histopathology has revealed abnormalities in the cortical grey-matter of MS patients that appear to be independent of white-matter lesions. A methodology to quantify neocortical injury and degeneration that yields cross-sectional and longitudinal metrics of cortical thickness and grey-matter/white-matter interface integrity both globally and regionally is presented and validated. MS patients with progressive disability showed greater decreases in cortical metrics compared to MS patients with stable disability.
The quantitative MRI analysis methods presented in this thesis are applicable to MRI data obtained in clinical trials of therapies for MS, have the necessary sensitivity and specificity to assess therapeutic efficacy, and provide new insights into disease pathogenesis and evolution.
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Paling, D. J. "Novel MRI techniques to investigate the pathophysiological mechanisms underlying disease progression and disability in multiple sclerosis". Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1420448/.
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Most patients with multiple sclerosis (MS) develop progressive disease. Progression is ominous as there are no drugs able to alter this inexorable accrual of disability. In this thesis the literature on the pathology of MS is reviewed. Experimental and pathological studies that suggest energy failure may be a significant cause of the neuroaxonal loss underlying progression are discussed. The thesis then describes magnetic resonance imaging studies designed to investigate the importance of energy failure in vivo. R2’ is a measure of magnetic field inhomogeneity, and is increased by deoxyhaemaglobin within the vasculature. Whole brain R2’ mapping found that R2’ in was reduced in lesions and in normal appearing white matter suggesting that oxidative metabolism may be decreased. Energy failure may also be secondary to insufficient blood flow to tissue. This was investigated using an arterial spin labelled MRI sequence. This study showed that blood flow and bolus arrival time were actually increased in white matter in MS. These results suggest that there may be widespread vasodilation, particularly in white matter, despite possible reduction in oxidative metabolism. Lastly, since sodium is maintained at a low concentration in cells by an energy intensive pump, increase in sodium concentration could indicate cellular energy failure. Whole brain sodium imaging showed increase in sodium concentration in lesions and cortical grey matter in all subgroups of MS, but increases in normal appearing white matter and deep grey matter in progressive MS only. Associations were seen between sodium concentrations and disability suggesting that sodium imaging is sensitive to the pathology underlying progression. As a whole the results suggest that in MS there are widespread metabolic abnormalities effecting all parts of the brain. Particularly with sodium MRI, it provides preliminary validation that this may be a technique sensitive to early, clinically relevant, and potentially reversible pathophysiology.
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Karpate, Yogesh. "Enhanced representation & learning of magnetic resonance signatures in multiple sclerosis". Thesis, Rennes 1, 2015. http://www.theses.fr/2015REN1S068/document.
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La sclérose en plaques (SEP) est une maladie auto-immune inflammatoire du jeune adulte causant des handicaps variables et progressifs irréversibles. Cette maladie est présente de manière prépondérante dans l’hémisphère nord. Cette thèse s’attache à la caractérisation et à la modélisation de signatures IRM multimodales des lésions de sclérose en plaques. L’objectif est d’améliorer les modèles de représentation de l’image et d’adapter les méthodes d’apprentissage pour la reconnaissance visuelle, dans le cas où des informations de haut niveau telles que les lésions SEP incluses dans l’IRM sont extraites. Nous proposons dans cette thèse un nouvel algorithme de normalisation d’intensité en IRM, particulièrement centré sur la normalisation d’images longitudinales multimodales, afin de produire des détections d’évolution de lésion robustes. Cette normalisation est centrée sur la modélisation de l’histogramme de l’image par un modèle de mixture de Gaussiennes robuste à la présence de lésions. Faisant suite à cet algorithme, nous proposons également deux nouvelles méthodes de détection de lésions SEP basées sur (1) une comparaison statistique du patient vis à vis d’une population de sujets contrôle et (2) un cadre probabiliste de détection basé sur un apprentissage d’une classe (tissus sains). Nous avons évalué les algorithmes proposés sur plusieurs jeux de données multi-centriques et vérifié leur efficacité dans la détection de lésionsMultiple Sclerosis (MS) is an acquired inflammatory disease, which causes disabilities in young adults and it is common in northern hemisphere. This PhD work focuses on characterization and modeling of multidimensional MRI signatures in MS Lesions (MSL). The objective is to improve image representation and learning for visual recognition, where high level information such as MSL contained in MRI are automatically extracted. We propose a new longitudinal intensity normalization algorithm for multichannel MRI in the presence of MS lesions, which provides consistent and reliable longitudinal detections. This is primarily based on learning the tissue intensities from multichannel MRI using robust Gaussian Mixture Modeling. Further, we proposed two MSL detection methods based on a statistical patient to population comparison framework and probabilistic one class learning. We evaluated our proposed algorithms on multi-center databases to verify its efficacy
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Wang, Chenyu. "Improving the specificity of quantitative neuroimaging biomarkers for monitoring disease progression and understanding disease mechanisms in multiple sclerosis with diffusion magnetic resonance imaging". Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17939.
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Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system (CNS) that is associated with progressive neurodegeneration. To better understand the dynamics of disease progression in individuals with MS, and to personalise treatment strategies, the development of quantitative in-vivo biomarkers is critical. Magnetic resonance imaging (MRI) is an essential technique that has been successfully embedded in the formal diagnostic criteria for MS since 2001. Conventional MRI techniques facilitate the demonstration of lesion dissemination in both space and time. Furthermore, conventional MRI metrics derived from quantitative analysis can predict disability progression in clinical trials. However, these imaging metrics are often criticised for their weak correlations with clinical outcomes at the individual level; and lack of specificity for the underlying pathological process(es). Despite successes in large group studies, the transition of quantitative neuroimaging to clinical practice as a tool for both monitoring disease progression and guiding therapeutic strategy has progressed slowly. In this thesis, a refined analysis framework that improves the specificity and clinical validity of MRI metrics, is described and evaluated. Specifically, multi-modal approaches that integrate advanced diffusion imaging and conventional structural metrics are investigated; and a potential composite biomarker of MS disease progression is proposed.
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Anderson, Valerie Margaret. "Assessment and optimisation of MRI measures of atrophy as potential markers of disease progression in multiple sclerosis". Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/5300/.
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There is a need for sensitive measures of disease progression in multiple sclerosis (MS) to monitor treatment effects and understand disease evolution. MRI measures of brain atrophy have been proposed for this purpose. This thesis investigates a number of measurement techniques to assess their relative ability to monitor disease progression in clinically isolated syndromes (CIS) and early relapsing remitting MS (RRMS). Presented, is work demonstrating that measurement techniques and MR acquisitions can be optimised to give small but significant improvements in measurement sensitivity and precision, which provided greater statistical power. Direct comparison of numerous techniques demonstrated significant differences between them. Atrophy measurements from SIENA and the BBSI (registration-based techniques) were significantly more precise than segmentation and subtraction of brain volumes, although larger percentage losses were observed in grey matter fraction. Ventricular enlargement (VE) gave similar statistical power and these techniques were robust and reliable; scan-rescan measurement error was <0.01% of brain volume for BBSI and SIENA and <0.04ml for VE. Annual atrophy rates (using SIENA) were -0.78% in RRMS and -0.52% in CIS patients who progressed to MS, which were significantly greater than the rate observed in controls (-0.07%). Sample size calculations for future trials of disease-modifying treatments in RRMS, using brain atrophy as an outcome measure, are described. For SIENA, the BBSI and VE respectively, an estimated 123, 157 and 140 patients per treatment arm respectively would be required to show a 30% slowing of atrophy rate over two years. In CIS subjects brain atrophy rate was a significant prognostic factor, independent of T2 MRI lesions at baseline, for development of MS by five year follow-up. It was also the most significant MR predictor of disability in RRMS subjects. Cognitive assessment of RRMS patients at five year follow-up is described, and brain atrophy rate was a significant predictor of overall cognitive performance, and more specifically, of performance in tests of memory. The work in this thesis has identified methods for sensitively measuring progressive brain atrophy in MS. It has shown that brain atrophy changes in early MS are related to early clinical evolution, providing complementary information to clinical assessment that could be utilised to monitor disease progression.
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Soon, D. "MRI evaluation of the anti-adhesion molecule antibody Natalizumab and the blood-brain barrier in Multiple Sclerosis". Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19424/.
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As Blood-brain barrier (BBB) breakdown is central to inflammatory lesion formation, it presents a potential target in the formulation of putative therapeutic agents in MS. The action of natalizumab, a monoclonal antibody acting at the BBB, is investigated through a phase III monotherapy trial (AFFIRM) and associated substudies. Subtle BBB disruption from non-inflamed lesions, which could contribute to axonal damage through leakage of inflammatory cells and associated mediators into surrounding parenchyma, is also studied. Introductory chapters (1-3) provide a brief overview of MS, clinical trials, magnetic resonance imaging (MRI), the BBB and natalizumab. Chapter four describes MRI results of AFFIRM- a 2 year multi-centre trial involving 942 patients. Compared with placebo, natalizumab reduced number of gadolinium (Gd)- enhancing lesions by 92%, new/enlarging T2-hyperintense lesions by 83%, and new T1- hypointense lesions by 76%. Chapter five describes a 57 patient AFFIRM trial substudy in which the influence of natalizumab on segmental atrophy was investigated. Atrophy was predominant in grey matter (GM) and was independent of lesion load. Fluctuations in white matter (WM) volume followed changes in inflammatory lesion load. Atrophy was not influenced by natalizumab. The effect of natalizumab on subtle BBB disruption (inferred by measuring the post-Gd %change in T1 weighted signal intensity) is studied in chapter 6. This AFFIRM substudy involved 40 patients (27 on natalizumab, 13 on placebo.) Although subtle BBB leakage was consistently detected in non-visibly enhancing lesions, natalizumab did not influence the degree of leakage. Chapter 7 describes a cross-sectional study which utilised post-Gd change in R1 (1/T1) as a marker BBB leakage. 19 patients (10 RRMS, 9 SPMS) were involved in this study. The subtle leakage observed from non-visibly enhancing lesions was distinct from leakage from visibly enhancing lesions. This was sustained over 60 minutes, greater in smaller lesions and in size-adjusted T1 hypointense lesions.
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Koubiyr, Ismail. "The reorganization of human brain networks in the early stages of multiple sclerosis". Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0152.
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Les troubles cognitifs sont fréquents dans la sclérose en plaques (SEP) mais leurs mécanismes sous-jacents sont encore mal connus. Les techniques d’IRM ont été indispensables pour essayer de mieux comprendre les substrats biologiques des processus cognitifs. L’objectif de cette thèse est de mieux comprendre les mécanismes physiopathologiques du fonctionnement cognitif dans les stades précoces de la SEP. Pour cela, nous avons étudié une cohorte de patients atteints de syndrome cliniquement isolé (SCI) pendant un an, en réalisant une batterie de tests neuropsychologiques ainsi qu’un examen IRM. Nous avons tout d’abord démontré une atteinte précoce de la substance grise, en particulier au niveau de l’hippocampe, se propageant vers le cortex après un an d’évolution. L’atteinte microstructurale précoce de l’hippocampe était capable de prédire sa perte de volume. Ensuite, nous nous sommes intéressés à la réorganisation des réseaux cérébraux fonctionnels à ce stade précoce de la maladie. En utilisant l’IRM fonctionnelle de repos, nous avons démontré une réorganisation cérébrale fonctionnelle précoce impliquant plusieurs régions cérébrales. Cette réorganisation était encore plus prononcée après un an d’évolution. Au même moment, nos patients présentaient un fonctionnement cognitif normal qui était associé au niveau de réorganisation cérébrale présente. Ces résultats suggèrent un mécanisme de compensation aux stades précoces de la pathologie. La relation entre ces modifications fonctionnelles et l’anatomie sous-jacente est inconnue dans la SEP. Nous avons ainsi décidé de combiner l’IRM fonctionnelle de repos et l’imagerie par tenseurs de diffusion pour étudier à la fois la connectivité fonctionnelle et la connectivité structurelle. En utilisant le paramètre de couplage structurel-fonctionnel, nous avons démontré un découplage, un an après l’apparition de la maladie, au niveau de trois réseaux cérébraux du repos (salience, visuel et somato-moteur). Ce découplage était observé alors même que les performances cognitives de nos patients étaient préservées et que la réorganisation fonctionnelle était présente. Ces résultats suggèrent que cette réorganisation fonctionnelle à ce stade, agissant comme un mécanisme de compensation, se produit à travers des connections anatomiques indirectes. Afin de confirmer ces résultats et de suivre l’évolution des réseaux cérébraux et leur impact sur la cognition, nous avons recontacté nos patients SCI pour un suivi à 5 ansCognitive impairment is frequent in multiple sclerosis (MS) but its underlying mechanisms are still poorly understood. MRI techniques have been a valuable tool to investigate the biological substrates of cognitive processes. The objective of this thesis was to better understand the pathophysiological mechanisms of cognitive functioning at the early stage of MS. We followed clinically isolated syndrome (CIS) patients for one year, using neuropsychological tests, conventional and more advanced MRI techniques. We first demonstrated a differential gray matter vulnerability at the beginning of MS with a pathological spread from the hippocampus towards the cortex. We showed that the first microstructural alterations taking place within the hippocampus were able to predict its future volume loss. After that, we were interested in the potential brain functional reorganization at this stage of the disease. Using resting-state functional MRI, we were able to demonstrate very early regional brain functional reorganization starting from the disease onset and becoming more pronounced after one year of evolution. We also noticed a preservation of cognitive performances in CIS patients, which we found was associated to more functional reorganization. These results suggested then a compensation mechanism at the first year after a CIS. However, the relationship between these functional changes and the underlying anatomy was still missing. Thus, we combined resting-state functional MRI and diffusion tensor imaging to represent both functional and structural connectivity. Using the structural-functional coupling parameter, representing the association between structural and functional connections, we showed a decoupling one year after the disease onset in three major networks (salience, visual and somatomotor networks). This decoupling was noticed while cognitive performances were preserved and functional reorganization present. These last results led us to suggest that the functional reorganization at this stage, acting as a compensation mechanism, occurs along indirect anatomical pathways. In order to confirm these results and further follow-up brain networks topology and its impact on cognition, we are currently calling back our CIS patients for their 5-year visit
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Böttcher, Rene. "Differenzierung von ZNS-Läsionen der Enzephalomyelitis disseminata mittels suszeptibilitätsgewichteter Magnetresonanzbildgebung (SWI)". Doctoral thesis, Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-223241.
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Die Magnetresonanztomographie stellt für die Detektion von zerebralen und spinalen Läsionen bei der Multiplen Sklerose die sensitivste bildgebende Methode dar und ist ein Instrument, die räumliche und zeitliche Dissemination der Erkrankung abbilden zu können. Die Spezifität des Verfahrens ist aber gering und die Applikation von MR-Kontrastmittel bei der Diagnostik zwingend notwendig.
Bei der suszeptibilitätsgewichteten Magnetresonanzbildgebung (SWI) handelt sich um ein MR-Verfahren, das Schwankungen der magnetischen Suszeptibilität in der Gradientenechosequenz nutzt, um einen Bildkontrast zu erzeugen. Dadurch ist es möglich, hochaufgelöst und sensitiv Magnetfeldinhomogenitäten zu detektieren.
In der vorliegenden prospektiven Studie wurden im Zeitraum von 2010 bis 2013 MRT-Untersuchungen unter Einschluss der suszeptibilitätsgewichteten Bildgebung in einem Kollektiv von 41 Patienten (33 weiblich, 8 männlich;; Durchschnittsalter 40 Jahre) mit gesicherter Multipler Sklerose und einem Vergleichskollektiv von 43 Patienten (28 weiblich, 15 männlich;; Durchschnittsalter 45 Jahre), bei denen weder bildgebend noch klinisch Hinweise auf eine Multiple Sklerose vorlagen, durchgeführt. Die Untersuchung wurde mit einem 1,5-Tesla-Magnetresonanz- tomographen realisiert. Das besondere wissenschaftliche Interesse galt dabei der „normal erscheinenden weißen Substanz“ (NAWM) und den zerebralen Läsionen. In der FLAIR-Sequenz wurden die MS-Läsionen und ROIs detektiert und markiert. Anschließend erfolgte die Übertragung in gleicher Schichthöhe auf die SWI-, T1w- und ADC-Sequenz. Zur Differenzierung von akuten und chronischen Läsionen
erfolgte im Untersuchungsablauf die intravenöse Gabe von Gadolinium-DTPA- Kontrastmittel.
Schon längere Zeit werden im wissenschaftlichen Diskurs krankheitsspezifische Veränderungen in der NAWM vor Auftreten der MS-Läsionen vermutet. Die Sensitivität der FLAIR-Sequenz ist aber scheinbar unzureichend. Mit der SWI- Bildgebung konnten statistisch signifikante SI-Unterschiede zwischen Referenz- und MS-Gruppe in der NAWM herausgearbeitet werden. Nach Kontrastmittelgabe wurden dabei keine Veränderungen der Signalintensität der NAWM in den beiden Gruppen festgestellt, was gegen die Hypothese einer primären Schrankenstörung in der Pathogenese der Erkrankung spricht.
Insgesamt wurden 669 Läsionen identifiziert. Es folgte eine Differenzierung in 11 KM-aufnehmende (ACM-) Läsionen, 546 nicht KM-aufnehmende (NACM-) Läsionen und 112 „black holes“ (BLH). Eine gezielte Auswertung der Phasen- und Magnitudenbilder wurde nicht durchgeführt. Besonders in den KM-anreichernden Läsionen (ACM) sind bereits vor der KM-Gabe statistisch erhöhte Signalintensitäten in der SWI-Sequenz nachweisbar. Dies könnte theoretisch für den Nachweis akuter Läsionen, ohne dass eine KM-Gabe notwendig ist, genutzt werden. Doch ist die Anzahl dieser Läsionen in der Untersuchung zu gering, um verlässliche Aussagen diesbezüglich machen zu können. Dafür sind weitere Studien notwendig.
Zusammenfassend betrachtet handelt es sich bei der SWI um ein hoch sensitives bildgebendes Verfahren, welches eine ausgezeichnete Differenzierung von ZNS- Läsionen ermöglicht und Veränderungen der NAWM bei der Enzephalomyelitis disseminata nachweisen kann. Es stellt somit eine sinnvolle Ergänzung zur konventionellen MS-Diagnostik dar und ist ein innovatives bildgebendes In-vivo- Verfahren zur weiteren Erforschung der Multiplen Sklerose.
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Müller, Katharina [Verfasser]. "Detailing intra-lesional venous lumen shrinking in multiple sclerosis investigated by sFLAIR MRI at 7-T / Katharina Müller". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1079841016/34.
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Campbell, Jamie. "A randomised controlled trial of efficacy of cognitive rehabilitation in multiple sclerosis : a cognitive, behavioural and MRI study". Thesis, University of Brighton, 2016. https://research.brighton.ac.uk/en/studentTheses/db2452c2-0feb-448d-9da1-57e3d5d12140.
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Multiple sclerosis is the most common cause of non-traumatic disability in young adults. In addition to the physical disability associated with the condition there exists significant non-motor symptoms. Cognitive dysfunction in multiple sclerosis is common and presents significant morbidity for patients. There is mounting evidence for neuroplasticity playing a role in limiting the functional impact of pathology in MS. However, the degree to which neuroplasticity can ameliorate the impact of cognitive dysfunction and the potential that exists for structured cognitive rehabilitation are largely unknown. Aims To explore the feasibility and efficacy of computerised, home-based cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and advanced structural and functional magnetic resonance imaging. Methods 38 patients with MS and evidence of cognitive impairment as defined as scores below the 5th centile for normative data on the Brief International Cognitive Assessment for MS test battery were enrolled in an open-design randomised, controlled, exploratory trial of computerised cognitive rehabilitation. Neuropsychological and MRI data were obtained at baseline (time 1) as well as immediately following a 6-week intervention period (time 2) and after an addition twelve week follow up period (time 3). Changes in cortical activations were explored using a visual n-back fMRI paradigm and microstructural changes were explored using quantitative magnetisation transfer imaging. Patients were randomly assigned to undergo 45-minutes of computerised cognitive rehabilitation (RehaCom software, n = 19) three times weekly for six weeks or to a control condition (natural history DVDs, n = 19). Results The n-back fMRI task was associated with robust cortical activations in known working memory networks. The spatial extent and magnitude of the activations were greater for the 2-back than the 1-back condition. At time 3 significant increases in activation were seen in both the 1-back and 2-back conditions in the treatment group relative to controls. In the 1-back task, increased activation was seen in the left frontal and right temporo-parietal regions (p < 0.05 FWEcorr). In the more demanding 2-back task, there was increased activation in the bilateral prefrontal cortex and right temporoparietal regions relative to control group at time 2 (p < 0.05 FWEcorr). No significant changes were observed on quantitative magnetisation transfer imaging. Compared to time 1, a significantly higher proportion of patients in the treatment group showed 10% or greater improvement in the Symbol Digits Modality Test (SDMT) at time 2 (x2 = 0.008) however no significant difference in cognitive performance was seen between the groups at time 3. Quality of life outcome measures did not significantly differ between the groups. Conclusion This study supports the hypothesis that home-based, computerised cognitive rehabilitation may be a feasible and effective approach to improving cognitive performance in patients with MS. The alterations in cortical activation in attention and executive centres are likely to represent more efficient neural processing. The changes at the microstructural level that underpin this adaptation may be beyond the resolution of current imaging techniques. Improvements in quality of life as a result of cognitive rehabilitation may result from improved work place or social performance, which may occur over a longer timeframe. Quality of life outcome measures may need to be conducted over a longer period of follow up.
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Brown, Andrew Peter. "Imaging neuroinflammatory processes with USPIO-MRI". Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:aa1b5add-6a05-44ff-a270-5c31630f6577.
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This thesis examines the utility of USPIO-MRI to provide a tool of tracking macrophage recruitment to sites of neuroinflammation within the CNS. Recruited macrophages and microglia resident in CNS tissue play a key role in the pathophysiology of a number of neuroinflammatory diseases such as neuropathic pain and multiple sclerosis. Under activated conditions, microglia and macrophages will phagocytose invading cells and CNS debris. It has been shown that ultrasmall superparamagnetic particles of iron oxide (USPIO), such as Sinerem, injected systemically, are engulfed by macrophages, which in turn migrate to sites of tissue injury. USPIOs can be visualised as a distinct reduction in signal intensity on T2* weighted MR images. However, there are still some issues regarding the distinction between iron-laden recruited macrophages and the entry of free iron across a permeable blood brain barrier (BBB) in disease cases. Hence, it was shown that intravenously injected Sinerem is cleared from the peripheral circulation within 24 hours, indentifying this as a time point as suitable for MCP-1 injection. Data showed that free USPIO can be visualised in the brain and that there is a linear relationship between Sinerem concentration and T2* signal intensity changes. MCP-1 induces macrophage recruitment to the site of microinjection and causes BBB breakdown at between 3 and 4 hours. In particular it was shown that T2* signal intensity changes are seen, in the presence of an intact BBB, as a result of Sinerem laden macrophages. This finding was verified by the co-localisation of ED-1 positive cells and Prussian blue positive regions. It was demonstrated that there is a strong correlation between T2* signal changes and the number of macrophages. This demonstrates that USPIO-MRI can be used to characterise macrophage infiltration in neuroinflammation in the presence of an intact BBB.
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Seppi, Dario. "Integration of advanced molecular analyses and magnetic resonance imaging for the identification of biomarkers of disease progression in multiple sclerosis". Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3427119.
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Background. In the last 15 years, it has become increasingly accepted that cerebral grey matter (GM) damage in MS is evident since early MS stages and provides the best correlate of the rate of clinical progression since early disease stages. The lack of substantial inflammatory infiltrates, complement deposition and blood brain barrier damage in MS cortical lesions led to the initial suggestion that the mechanisms underlying GM and white matter (WM) pathology substantially differ and that activated microglia are the dominant effector cell population causing GM damage. Furthermore, in the last decade, post-mortem studies have revealed that the extent of meningeal inflammation associates positively with subpial cortical demyelination and disease progression, suggesting that chronic immune activity in the subarachnoid compartment plays a key role in mediating damage in the adjacent cerebral cortex of affected patients. Factors released by immune cells circulating in the CSF and/or colonizing the subarachnoid space may diffuse across the pial membrane, inducing a gradient of glia and neuronal pathological alterations, directly and/or indirectly through activated microglia.
Aim of the study. To combine CSF molecular and protein analyses with advanced MRI imaging techniques, able to better identify cortical grey matter demyelination, in order to identify potential early biomarkers of GM pathology and disease progression with prognostic and predictive value and to obtain information on the biological and immunological mechanisms that link the inflammatory process of the GM and the progressive neurodegeneration
Methods. Two independent cohorts of MS patients have been recruited and followed by the MS Centre of Padova. The first cohort of MS patients, composed of 35 patients and 5 controls was recruited retrospectively between February 2009 and September 2011 and followed by a detailed neurological and clinical follow-up. The second cohort of 31 patients and 13 controls was collected prospectively from January 2014 to May 2015. The patients, at their disease onset or in the very early phase of the disease, underwent a complete diagnostic work-up comprehensive of clinical evaluation, lumbar puncture and MRI evaluation inclusive of non-conventional sequences. By using the immuno-assay Bio-Plex System technique (Biorad - Bio-Plex Pro Human Chemokine panel 40-plex) we performed a protein analysis of the presence and levels of inflammatory molecules in both cohorts. In the second cohort we carried out also a gene expression analysis of the matched cellular fraction (using pre amplification real-time PCR for a panel of genes of interest).
Results. CSF protein analysis of the first cohort of MS patients reveal higher levels of proinflammatory cytokines CXCL13 (p=0,00006), CCL19 (p=0,0019), CCL1 (p=0,00018), and CCL22 (0.0009) compared to controls. Protein analysis on our second cohort pointed out an important increase of CXCL13, CXCL10, CXCL11 and CCL2 in MS population compared to controls. After stratification according to GM pathology we reported an increase of CXCL13 protein levels in the MS subgroup with higher cortical demyelination. Gene expression analysis reveals a significant increase in MS patients for CD20, CD138 and LTa compared to controls supporting the hypothesis of a key role of a B-cell response and lymphoid neogenesis in MS pathology
Conclusions. Combined CSF analysis and MRI analysis suggested that B cell immune response may play an important role in MS since the disease onset and correlates with the level of intrathecal inflammation and cortical pathology. A more detailed analysis of the CSF biomarkers suggested in the current study might provide, in addition to MRI optimization, a better indication of severity of disease process that characterized GM pathology and important tools in predicting/monitoring the evolution of the disease.Presupposti dello studio. Studi istopatologici e neuroradiologici hanno dimostrato, soprattutto negli ultimi 15 anni come la sclerosi multipla, considerata classicamente una patologia elettiva della sostanza bianca, sia una patologia caratterizzata da un coinvolgimento, fin dalle prime fasi di malattia, anche della sostanza grigia corticale e profonda che ben correla con il quadro di disabilità fisica e cognitiva ampiamente descritto. Dal punto di vista istopatologico tale coinvolgimento è caratterizzato dalla presenza di lesioni corticali che si distinguono per una minor componente infiammatoria, per un’assenza di danno a carico della barriera ematoencefalica e per un minor deposito di fattori del complemento. Alla luce di tale descrizione sembra che i meccanismi che sottendono il danno a carico della sostanza grigia differiscano almeno in parte da quelli osservati a carico della sostanza bianca. In particolare è stata osservata un’associazione tra lesioni corticali e la presenza di infiltrati infiammatori meningei correlata ad una maggiore disabilità clinica. È stato quindi evidenziato come molecole pro-infiammatorie rilasciate dalle cellule infiammatorie residenti nelle meningi diffondano attraverso lo spazio subaracnoideo e agiscono, direttamente o indirettamente attivando la componente microgliale, sulla adiacente corteccia cerebrale determinando un gradiente di danno corticale. Obiettivi. L’obiettivo di questo studio è stato quello di verificare la presenza di possibili potenziali biomarcatori di danno corticale mediante l’applicazione combinata di: a) tecniche avanzate di analisi proteica e analisi molecolare applicate allo studio del liquido cerebro spianale; b) tecniche non convenzionali di risonanza magnetica, in grado di caratterizzare il danno a carico della sostanza grigia sia focale che diffuso. Materiali e metodi. Sono state arruolate due coorti di pazienti: la prima studiata retrospettivamente era composta da 35 pazienti e 5 controlli; la seconda arruolata nello studio con un approccio di tipo longitudinale era composta da 31 pazienti e 13 controlli. Tutti i pazienti erano caratterizzati da un esordio relativamente recente e la precedente somministrazione di terapie immunomodulanti rappresentava un criterio di esclusione. Tutti i pazienti si sono sottoposti ad un iter diagnostico completo comprensivo di valutazione clinica, esami di laboratorio, esame del liquido cerebrospinale e risonanza magnetica comprensiva di sequenze non convenzionali per verificare la presenza di lesioni della sostanza grigia. Lo studio del liquido cerebrospinale prevedeva inoltre uno studio di analisti proteica mediante immuno-assay (Bio-Plex System technique Biorad - Bio-Plex Pro Human Chemokine panel 40-plex) per lo studio di 40 citochine/chemochine e uno studio di analisi di gene expression. Risultati. L’analisi proteica del liquor nella prima coorte ha evidenziato la presenza di elevati valori di CXCL13 (p=0,00006), CCL19 (p=0,0019), CCL1 (p=0,00018), e CCL22 (0.0009) rispetto alla popolazione di controllo. L’analisi proteica della seconda coorte ha evidenziato, sempre rispetto alla popolazione di controllo, un aumento delle seguenti citochine: CXCL13, CXCL10, CXCL11 e CCL2. Dopo stratificazione in base al carico corticale abbiamo evidenziato nei pazienti con un maggior coinvolgimento della sostanza grigia un aumento dei livelli proteici di CXCL13 e una maggior espressione di CD20, CD138, CXCL13 and LTa a supporto di un ruolo della risposta infiammatoria mediata dai linfociti B. Conclusioni. L’analisi combinata di liquor e risonanza magnetica suggerisce che la risposta immunologica mediata dai linfociti B gioca un ruolo importante nella patogenesi della sclerosi multipla e che il livello di infiammazione intratecale ben correla con la patologia corticale. I risultati del nostro studio suggeriscono quindi che l’uso di biomarker liquorali potrebbero essere di supporto nella caratterizzazione della patologia corticale nella sclerosi multipla.
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Planche, Vincent. "Pathophysiology and imaging of early memory impairment in multiple sclerosis". Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0392/document.
Texto completoResumen
Les troubles mnésiques sont fréquents dans la sclérose en plaques (SEP) mais leurs substrats anatomique et biologique sont mal connus. L’objectif de cette thèse translationnelle était de comprendre les mécanismes physiopathologiques des troubles mnésiques à la phase précoce de la SEP, avec pour perspective de trouver de nouvelles cibles thérapeutiques et de définir de nouveaux marqueurs d’imagerie. Nous avons réalisé une analyse neuropsychologique et IRM de patients atteints de forme précoce de SEP et nous avons étudié des souris à la phase précoce d’une encéphalomyélite auto-immune expérimentale (EAE, le modèle animal de la SEP) avec une combinaison d’expériences comportementales, d’IRM, histologiques, électrophysiologiques et pharmacologiques. Nous avons démontré que l’atteinte hippocampique était précoce dans l’histoire de la maladie et qu’elle était corrélée au déclin mnésique des patients atteints de SEP. Nous avons identifié chez les souris EAE que la structure et la fonction du gyrus denté étaient plus vulnérables que les autres sous-champs de l’hippocampe au stade précoce de la maladie et nous avons transposé cette découverte à la pathologie humaine en démontrant une perte des capacités de pattern separation chez des patients atteints de forme précoce de SEP. Du point de vue mécanistique, nous avons démontré que l’activation microgliale précoce était responsable de l’atteinte du gyrus denté et des troubles mnésiques dans l’EAE et que cette cascade physiopathologique pouvait être prévenue grâce à un traitement par minocycline. Du point de vue de l’imagerie, nous avons également démontré que l’atteinte microstructurale de l’hippocampe ainsi que la neurodégénérescence précoce du gyrus denté pouvaient être étudiées in vivo en tenseur de diffusion (DTI). Nous travaillons à la mise en place de méthode encore plus spécifique par l’imagerie de densité neuritique et d’orientation/dispersion (NODDI). Nos résultats relient l’atteinte mnésique précoce de la SEP à une neurodégénérescence sélective du gyrus denté. Ce processus physiopathologique peut être prévenu en inhibant l’activation microgliale chez les souris EAE et peut être étudié in vivo grâce au DTI chez la souris comme chez l’homme, offrant d’évidentes perspectives cliniques dans la prise en charge des patients atteints de SEPMemory impairment is frequent in multiple sclerosis (MS) but its anatomical and biological substrates are poorly understood. The objective of this translational thesis was to understand the pathophysiological mechanisms of early memory impairment in MS, to find new potential therapeutic targets and to define new imaging biomarkers related to memory impairment. We used neuropsychological and MRI experiments in patients with early MS and we explored experimental autoimmune encephalomyelitis (EAE) mice (a mouse model of MS) at the early stage of the disease with a combination of behavioral, in vivo MRI, histological, electrophysiological and pharmacological approaches. In patients with MS, we demonstrated that hippocampal damage occurs early during the course of the disease and that it correlates with memory impairment. In EAE-mice, we identified that dentate gyrus structure and function are more vulnerable than other hippocampal subfields at the early stage of the disease and we translated this finding back to humans by demonstrating loss of pattern separation performances in patients with early MS. From a mechanistic point of view, we demonstrated that early microglial activation causes dentate gyrus disruption and memory impairment in EAE-mice and that this pathophysiological cascade can be prevented with minocycline. From the imaging point of view, we demonstrated that hippocampal microstructural damage and early dentate gyrus degeneration can be monitored in vivo with diffusion tensor imaging (DTI). We are currently developing more specific imaging approaches with optimization of the Neurite Orientation Dispersion and Density Imaging (NODDI) to assess hippocampal subfields. Our results link early memory impairment in MS to a selective disruption of the dentate gyrus. We were able to prevent this neurodegenerative process with microglial inhibitors in EAE-mice and to capture these features non-invasively with DTI in both humans and rodents, paving the way toward new clinical perspectives in MS
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VACCHI, LAURA. "Imaging Cognitive Network Dysfunction in Multiple Sclerosis Patients with Relapse-Onset Clinical Phenotypes". Doctoral thesis, Università Vita-Salute San Raffaele, 2016. http://hdl.handle.net/10281/287950.
Texto completoResumen
Cognitive impairment strongly affects people with multiple sclerosis (MS). It comprises multifactorial symptoms and no consistent treatments are available to date. Although cognitive impairment has been observed in all stages of the disease, the majority of studies mainly focused on a specific clinical phenotype (primarily relapsing-remitting MS) or did not differentiate between MS subtypes. Advanced magnetic resonance imaging (MRI) techniques are providing useful measures of functional and structural abnormalities in patients with MS, allowing to overcome the limits of conventional MRI. This thesis wished to improve the understanding of the mechanisms responsible for the accumulation of cognitive dysfunction in patients with relapse-onset MS by combining different advanced structural and functional MRI techniques.
First, we applied functional MRI (fMRI) to assess brain functional reorganization in relation to different cognitive tasks (face encoding and N-back) in patients with the main relapse-onset clinical phenotypes. We also explored the relationship between functional network alterations and clinical, cognitive, behavioural and structural MRI measures of disease-related damage. Our results provide new evidence for the debate about adaptive/maladaptive functional reorganization in MS, specifically in relation to the clinical and cognitive characteristics of MS phenotypes.
Second, the investigation of resting state default mode network (DMN) functional connectivity enabled us to highlight that different modulations of DMN recruitment lead to different clinical profiles and manifestations. Moreover, functional connectivity of specific DMN areas (hippocampi) was found to be central for the assessment of important cognition-related aspects, such as depression.
Finally, by applying voxel-wise MRI methods (VBM and TBSS) we explored the extent and distribution of brain GM atrophy and WM microstructural alterations in adult MS patients according to their age of disease onset, and we made some assumptions about the possible presence of pathophysiological mechanisms related to age of MS onset, that suggests a preserved reserve for structural plasticity that could modulate the structural and functional brain organization, in order to preserve or slow-down MS-related dysfunction.
To conclude, the application of advanced MRI techniques allowed us to improve our knowledge on neuropsychological features in patients with relapse-onset MS.
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Gong, Qi-Yong. "Application of MRI and the Cavalieri method in studies of the IUGR, cervical carcinoma, multiple sclerosis and cerebral glioma". Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366702.
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Hill, A. M. "Longitudinal changes in metabolite concentrations and lesion development in EAE and Multiple Sclerosis using 1H-MR Spectroscopy and MRI". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1554670/.
Texto completoResumen
Multiple Sclerosis (MS) is an inflammatory demyelinating disease affecting the grey matter (GM) and white matter (WM) of the central nervous system resulting in progressive neurological deficits and clinical disability. Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS, can be investigated with magnetic resonance (MR) to address the clinical need to understand mechanisms of the MS disease course. However, longitudinal MR studies with EAE are currently under-explored. This thesis investigated longitudinal changes in metabolite concentrations and lesion development, in relation to neurological deficits in EAE, using 9.4T MRI and 1H-MRS and compared the findings using similar methods in early MS. The pre-clinical study assesses five time-points of EAE disease progression. The results suggest that after the immunisation, but before visible signs of neurological deficits, higher N-acetyl-aspartate concentration [NAA] predicts the severity of late-stage neurological deficits in EAE where a lower fractional anisotropy (FA) and histology indicate microstructural deficits. The results correspond with histology markers where EAE animals severely affected by recombinant myelin oligodendrocyte glycoprotein (rMOG), had an increase of mitochondria at the Pre-symptomatic and Onset time-points compared to controls. These findings were compared to a longitudinal analysis of clinically isolated syndrome (CIS) conversion to clinically definite MS (CDMS), where CIS patients with higher [NAA] 1 year after presenting with symptoms, develop a more severe MS disease course at 15 years after the onset of MS. There was also an interaction between new T2-weighted (T2-w) lesions and [tNAA] at 1 year after CIS onset which was the strongest indicator of differences between Relapsing Remitting MS and Secondary Progressive MS disease courses at 15 years. This may suggest that early [tNAA] changes could be used as a biomarker for long-term disease severity. The association between [NAA] and disability-score in EAE, at the Pre-symptomatic time-point, with histological evidence, as well as the interaction between early [NAA] and new T2-w lesions and disability severity and course, suggests that [NAA] may reflect pathological processes relevant to MS disease course and treatment targets.
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Brownlee, Wallace J. "Understanding long-term disability in multiple sclerosis : a clinical, MRI and genetic study in patients with clinically isolated syndrome". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10040077/.
Texto completoResumen
This thesis concerns a 15 year follow-up study of a cohort of people with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). I investigate (1) how MRI can be used to improve the diagnosis of MS around the time of CIS; (2) early MRI predictors of long-term disease course in people with CIS; and (3) mechanisms responsible for long-term disability and disease progression in relapse-onset MS. There has been significant evolution of the diagnostic criteria for MS in recent years. I examined the influence of changing diagnostic criteria for MS by retrospectively applying the McDonald criteria in the CIS cohort. I found that MS can be diagnosed significantly earlier in CIS patients using the McDonald criteria. I investigated two possible modifications to dissemination in space (DIS) criteria: firstly whether lesions in the symptomatic region should be included in DIS; and secondly whether the number of periventricular lesions in DIS criteria should be increased from 1 to 3. Including lesions in the symptomatic region improved the performance of MRI criteria but increasing the number of periventricular lesions in DIS did not improve diagnostic accuracy or specificity. These findings will inform future revisions to the diagnostic criteria for MS. MS-related disability is frequently referable to the spinal cord. I investigated early brain and spinal cord MRI abnormalities in the CIS cohort and found that spinal cord measures explained more of the disability after 5 years than brain MRI measures. Asymptomatic spinal cord lesions at the time of presentation in patients with a non-spinal CIS were the strongest early MRI predictor of disability after 5 years. These findings were then confirmed with long-term follow-up: spinal cord lesions at the time of presentation with CIS and new spinal cord lesions after 1 year and 3 years were associated with both physical disability and secondary progressive disease course after 15 years. These findings suggest that spinal cord MRI may provide important prognostic information in people with CIS and early MS. Early spinal cord damage may be an important mechanism contributing to long-term disability and disease progression in relapse-onset MS. Disease course heterogeneity in MS remains poorly explained. I investigated the influence of HLA-DRB1*15:01 on disease course and MRI measures of inflammation and neurodegeneration in the CIS cohort. Carriage of the HLA-DRB1*15:01 allele was associated with a faster accrual of disability, greater inflammatory disease burden and a faster rate of brain atrophy over the 15 year follow-up period. The HLA-DRB1*15:01 allele may not only influence the susceptibility to MS but also the disease phenotype and long-term clinical course. Neuroaxonal energy failure is thought to be central to disease progression in MS. I applied the novel metabolic imaging method sodium (23Na) MRI in patients followed up after 15 years to investigate the relationship of brain sodium accumulation in vivo with long-term disease course and disability. I found evidence of sodium accumulation in grey matter, in normal-appearing white matter and in lesions in people who developed MS. Cortical grey matter sodium concentration was associated with physical disability and cognitive performance at 15 years, even after adjusting for brain atrophy. 23Na-MRI should be investigated further as a possible outcome measure in future neuroprotection trials.