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Microcosms were constructed from aquifer sediment samples taken from an actively degrading chlorinated solvent contaminated site located in Virginia Beach, Virginia. The objective of this study was to determine if and how the addition of cyclodextrin (CD) affects reductive dechlorination of chlorinated ethenes. After chlorinated solvent degradation rates were established in anaerobic and aerobic microcosms, 100 mg/L of CD solution was added for a period of 21 days. CD was then removed after 26 days to simulate the degradation response of the aquifer in a post CD injection environment. Degradation rates were determined by analyzing PCE, TCE, and cis-DCE concentration data over the various phases of the experiment. Results from this study indicated that chlorinated solvent degradation could be either impaired or facilitated by the addition of CD. CD appeared to stimulate one anaerobic microcosm (IY-2c) where daughter production had not previously occurred. The activity of this microcosm was greatly enhanced by the addition of CD (0 uM/day to 13.89 uM/day). However, biotransformation of PCE in another anaerobic microcosm in which reductive dechlorination was occurring, ceased after the addition of CD (IY-1a). In a third group of microcosms the rate and extent of reductive dechlorination was greatly enhanced by the addition of CD. The effect of adding CD was also found to be highly dependent on the redox conditions in the microcosm, specifically if the conditions were strongly reducing. The most active microcosms, found in the Aerobic Group, also had the lowest ferrous iron concentrations (3.57 mg/L for BY-1a, 2.25 mg/L for BY-1b, and 0.41 mg/L for BY-1c). The microcosm (IY-2b) that showed no daughter production had the highest level of ferrous iron (44.22 mg/L). This study presents a qualitative approach to the affect of CD on MNA. / Master of Science

Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing perfusion-based imaging protocols. Using this method, we examined transport associated with invasion in a murine GL261 cell line. We found that elevated interstitial fluid velocity magnitudes, decreased diffusion coefficients and regions with accumulating flow were significantly associated with invasion. We tested the validity of our invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions indicating location-specific structures may drive both interstitial flow and corresponding invasion heterogeneities. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Over-expression of VEGF-C in the tumor microenvironment neither enhanced drainage nor altered invasion in comparison to our control, indicating other tumor-secreted growth factors, such as VEGF-A, may play a larger role in mediating flow and invasion. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease. / Doctor of Philosophy / Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing imaging projects. Using this method, we examined transport associated with cancer cell invasion in a mouse tumor cell line. We found that interstitial fluid speeds were elevated while diffusion was decreased in regions of invasion. Further, regions that had interstitial fluid flow congregation were significantly associated with invasion. We tested the validity of these invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions, indicating location-specific structures may drive both interstitial flow and invasion differences. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Following administration of a meningeal lymphatic-relevant protein, we saw no changes in flow or invasion in comparison to our untreated control, indicating other tumor-secreted proteins may play a larger role in these responses. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease.

L’analyse des systèmes naturels globaux est divisée selon les organismes régionaux, nationaux et internationaux. Leurs travaux sont encadrés par une gestion scientifique et juridique notamment par des directives tel que la DCE ou INSPIRE, basée sur la communication. La comparaison des données d’origines différentes et sans prise en compte des frontières n’est possible qu’à l’aide d’une harmonisation fondée sur les normes internationales. La carte est à ce titre un outil de transmission de l’information organisée à partir des bases de données.Cette thèse propose une analyse sémiologique de la représentation cartographique qui traite de la thématique de la gestion de l’eau dans un cadre européen. Il s’agit de comprendre et d’interpréter la mise en oeuvre des processus de communication basés sur les cartes ; la Hongrie et la France sont prises comme exemple.L’harmonisation est nécessaire mais en même temps très difficile à mettre en place au sein d’un monde où les disparités sont très grandes. Les compromis nécessaires à l'harmonisation et à l'uniformisation du langage cartographique impliquent des concessions de la part des acteurs mais aussi des producteurs de cartes.L’importance des innovations dans la visualisation cartographique aboutissant à une meilleure communication n’est pas encore reconnue à l’heure actuelle. Le public, quel qu’il soit, est souvent habitué à une représentation traditionnelle ; pourtant les effets que l’on peut ajouter à une carte, fruits de l’innovation technologique, ouvrent de nouveaux horizons pour la cartographie et peuvent servir de nouvelles bases au raisonnement dans la prise de décisions. / Water, which is one of our most important natural resources, stops at neither political nor artificial boundaries. This is why it is necessary to treat it globally instead of the present situation, where water is managed nationally and regionally. A possible solution for this is an international unified water management system, and effective information is a key requirement for this to happen. Maps contain visual information which is independent of language, and map visualization is an important tool of communication. Therefore I have been comparing two European Union countries (France and Hungary) to understand the processes of map communication in relation to EU regulations. The first objective of my research has been the examination of how far the harmonization of map communication has been achieved in the European directives, particularly concerning water-related directives. Secondly, to the extent that harmonization has not occurred, I have investigated into the reasons why this has happened and whether there are any solutions to this issue. Effectiveness of map-based communication is closely related to uniform data systematization. This is why I have endeavored to discover and develop a harmonizationhelping system for visualization. Finally, I have examined whether, in this legally-regulated research environment, there is the possibility of innovative rather than traditional map representations. As results I gave an overview of the European directives and projects, and I examined the relations between them. At the same time I determined the role of the cartographer concerning the directives. I created an examining system based on the rules of the French and Hungarian thematic cartography. I made certain that the directives are necessary but not sufficient conditions of harmonized map communication. The necessary condition of this is a uniform and harmonized system of thematic data. I verified that the maps created by existing processes do not meet the claims of the three different user circles aimed at by the WFD. I created my own communicative model for maps associated with water after studying Robinson-Petchenik-and Kolácný’s communicative models. I took into consideration every element of map-forming, which may have an influence on the decision made based on the map. I developed innovative prototypes for certain types of WFD maps to the general public and decision-makers. / Elsisorban szeretnék köszönetet mondani témavezetiimnek Philippe Quodverte-nek és José Jesús Reyes Nunez-nek, akik a doktori kezdetétil tanácsaikkal folyamatosan segítettek. Philippe Quodverte-nek külön szeretném megköszönni, hogy Erasmusos orléans-i tartózkodásom után három évvel újbóli támogatásáról biztosított és elvállalta a doktori témám vezetését, illetve azt a türelmet, amivel segített a francia doktori kutatásra vonatkozó eliírások és térképészeti hagyományok elsajátításában. Nagyon élveztem a vele való beszélgetéseket és térképészeti eszmecseréinket. Emellett köszönettel tartozom Zentai Lászlónak és Verebiné Fehér Katalinnak a nekem nyújtott segítségükért és hasznos tanácsaikért, illetve az ELTE Térképtudományi és Geoinformatikai Tanszék minden munkatársának volt tanáraimnak, akik támogatásával jutothattam el a doktoriig. Továbbá köszönöm Guillame Giroir-nak, a Földrajzi Doktori Iskola (CEDETE) vezetijének, hogy befogadott csapatába, és részese lehetek a CEDETE életének. Köszönet az Orléans-i Egyetemen kollégáimnak Anabelle Mas-nak, Stéphane Grivel-nek, Frank Guéritnek és Bertrand Sajaloli-nak, akik tanácsaikkal támogattak és segítették munkámat. Külön köszönet Matthieu Lee-nek, a CEDETE térképészének, aki észrevételeivel segítette a doktoriban bemutatott térképek elkészítését. Külön szeretném megköszönni mindazoknak, akik magyar és francia részril segítettek a Víz Keretirányelv és az INSPIRE végrehajtásának megismerésében, illetve az adatok elérésében, azaz név szerint François Robida (BRGM), Janik Michon (ONEMA), Jelinek Gabriella (Vidékfejlesztési Minisztérium), Tahy Ágnes (VKKI). Köszönettel tartozom Vikor Zsuzsának a dolgozat nyelvhelyességének ellenirzéséért. Köszönöm emellett családomnak, szüleimnek, nagyszüleimnek és testvéremnek, hogy bátorítottak és mellettem álltak. Nem utolsó sorban szeretném megköszönni doktorandusz társaimnak, Anh Tu-nak, Cristina-nak, Sylvain-nak, Eszternek, és barátaimnak, Virgine-nek Anabella-nak, Alexandranak, Chloë-nak és Dávidnak, hogy a nehéz pillanatokban segítettek és jó tanácsokkal láttak el. Külön köszönet Virginie Anne-nak a francia összefoglaló nyelvhelyességének ellenirzéséért és baráti támogatásáért.

L'imagerie de perfusion permet un accès non invasif à la micro-vascularisation tissulaire. Elle apparaît comme un outil prometteur pour la construction de biomarqueurs d'imagerie pour le diagnostic, le pronostic ou le suivi de traitement anti-angiogénique du cancer. Cependant, l'analyse quantitative des séries dynamiques de perfusion souffre d'un faible rapport signal sur bruit (SNR). Le SNR peut être amélioré en faisant la moyenne de l'information fonctionnelle dans de grandes régions d'intérêt, qui doivent néanmoins être fonctionnellement homogènes. Pour ce faire, nous proposons une nouvelle méthode pour la segmentation automatique des séries dynamiques de perfusion en régions fonctionnellement homogènes, appelée DCE-HiSET. Au coeur de cette méthode, HiSET (Hierarchical Segmentation using Equivalence Test ou Segmentation hiérarchique par test d'équivalence) propose de segmenter des caractéristiques fonctionnelles ou signaux (indexées par le temps par exemple) observées discrètement et de façon bruité sur un espace métrique fini, considéré comme un paysage, avec un bruit sur les observations indépendant Gaussien de variance connue. HiSET est un algorithme de clustering hiérarchique qui utilise la p-valeur d'un test d'équivalence multiple comme mesure de dissimilarité et se compose de deux étapes. La première exploite la structure de voisinage spatial pour préserver les propriétés locales de l'espace métrique, et la seconde récupère les structures homogènes spatialement déconnectées à une échelle globale plus grande. Etant donné un écart d'homogénéité $\delta$ attendu pour le test d'équivalence multiple, les deux étapes s'arrêtent automatiquement par un contrôle de l'erreur de type I, fournissant un choix adaptatif du nombre de régions. Le paramètre $\delta$ apparaît alors comme paramètre de réglage contrôlant la taille et la complexité de la segmentation. Théoriquement, nous prouvons que, si le paysage est fonctionnellement constant par morceaux avec des caractéristiques fonctionnelles bien séparées entre les morceaux, HiSET est capable de retrouver la partition exacte avec grande probabilité quand le nombre de temps d'observation est assez grand. Pour les séries dynamiques de perfusion, les hypothèses, dont dépend HiSET, sont obtenues à l'aide d'une modélisation des intensités (signaux) et une stabilisation de la variance qui dépend d'un paramètre supplémentaire $a$ et est justifiée a posteriori. Ainsi, DCE-HiSET est la combinaison d'une modélisation adaptée des séries dynamiques de perfusion avec l'algorithme HiSET. A l'aide de séries dynamiques de perfusion synthétiques en deux dimensions, nous avons montré que DCE-HiSET se révèle plus performant que de nombreuses méthodes de pointe de clustering. En terme d'application clinique de DCE-HiSET, nous avons proposé une stratégie pour affiner une région d'intérêt grossièrement délimitée par un clinicien sur une série dynamique de perfusion, afin d'améliorer la précision de la frontière des régions d'intérêt et la robustesse de l'analyse basée sur ces régions tout en diminuant le temps de délimitation. La stratégie de raffinement automatique proposée est basée sur une segmentation par DCE-HiSET suivie d'une série d'opérations de type érosion et dilatation. Sa robustesse et son efficacité sont vérifiées grâce à la comparaison des résultats de classification, réalisée sur la base des séries dynamiques associées, de 99 tumeurs ovariennes et avec les résultats de l'anapathologie sur biopsie utilisés comme référence. Finalement, dans le contexte des séries d'images 3D, nous avons étudié deux stratégies, utilisant des structures de voisinage des coupes transversales différentes, basée sur DCE-HiSET pour obtenir la segmentation de séries dynamiques de perfusion en trois dimensions. (...) / Dynamical contrast enhanced (DCE) imaging allows non invasive access to tissue micro-vascularization. It appears as a promising tool to build imaging biomarker for diagnostic, prognosis or anti-angiogenesis treatment monitoring of cancer. However, quantitative analysis of DCE image sequences suffers from low signal to noise ratio (SNR). SNR may be improved by averaging functional information in large regions of interest, which however need to be functionally homogeneous. To achieve SNR improvement, we propose a novel method for automatic segmentation of DCE image sequence into functionally homogeneous regions, called DCE-HiSET. As the core of the proposed method, HiSET (Hierarchical Segmentation using Equivalence Test) aims to cluster functional (e.g. with respect to time) features or signals discretely observed with noise on a finite metric space considered to be a landscape. HiSET assumes independent Gaussian noise with known constant level on the observations. It uses the p-value of a multiple equivalence test as dissimilarity measure and consists of two steps. The first exploits the spatial neighborhood structure to preserve the local property of the metric space, and the second recovers (spatially) disconnected homogeneous structures at a larger (global) scale. Given an expected homogeneity discrepancy $\delta$ for the multiple equivalence test, both steps stop automatically through a control of the type I error, providing an adaptive choice of the number of clusters. Parameter $\delta$ appears as the tuning parameter controlling the size and the complexity of the segmentation. Assuming that the landscape is functionally piecewise constant with well separated functional features, we prove that HiSET will retrieve the exact partition with high probability when the number of observation times is large enough. In the application for DCE image sequence, the assumption is achieved by the modeling of the observed intensity in the sequence through a proper variance stabilization, which depends only on one additional parameter $a$. Therefore, DCE-HiSET is the combination of this DCE imaging modeling step with our statistical core, HiSET. Through a comparison on synthetic 2D DCE image sequence, DCE-HiSET has been proven to outperform other state-of-the-art clustering-based methods. As a clinical application of DCE-HiSET, we proposed a strategy to refine a roughly manually delineated ROI on DCE image sequence, in order to improve the precision at the border of ROIs and the robustness of DCE analysis based on ROIs, while decreasing the delineation time. The automatic refinement strategy is based on the segmentation through DCE-HiSET and a series of erosion-dilation operations. The robustness and efficiency of the proposed strategy are verified by the comparison of the classification of 99 ovarian tumors based on their associated DCE-MR image sequences with the results of biopsy anapathology used as benchmark. Furthermore, DCE-HiSET is also adapted to the segmentation of 3D DCE image sequence through two different strategies with distinct considerations regarding the neighborhood structure cross slices. This PhD thesis has been supported by contract CIFRE of the ANRT (Association Nationale de la Recherche et de la Technologie) with a french company INTRASENSE, which designs, develops and markets medical imaging visualization and analysis solutions including Myrian®. DCE-HiSET has been integrated into Myrian® and tested to be fully functional.

L’insuffisance placentaire est une pathologie grave avec un diagnostic souvent trop tardif empêchant la mise en place de thérapeutiques efficaces. Le but de ce travail de Thèse est de développer chez la rate gestante et de transposer à l’Homme des outils d’IRM fonctionnelle (IRMf) placentaire qui permettrait une quantification de la perfusion placentaire en pratique clinique.Matériels et méthodes : Trois études en IRMf font partie de cette Thèse.Les deux premières ont été réalisées sur un modèle murin. Une séquence dynamique avec injection d’un agent de contraste (DCE) a été développée avec une particule de fer de type SPIO dans un modèle chirurgical d’hypoperfusion placentaire chronique, avec mesure de la perfusion placentaire f en ml/min/100ml et de la fraction volumique (Vb) en %. Une autre technique d’IRMf a été développée avec l’Arterial Spin Labeling (ASL) permettant d’estimer la perfusion placentaire en ml/min/100g sans injection de produit de contraste exogène. La dernière étude était une recherche translationnelle. Elle a consisté au développement de séquences de DCE avec injection de chélate de gadolinium, pour obtenir la perfusion f en ml/min/100ml et la fraction volumique en %. Nous avons également étudié, au décours de cette étude, la pharmacocinétique materno-fœtale du chélate de gadolinium.Résultats : Chez l’animal en DCE avec SPIO, notre étude nous a permis de montrer qu'il était possible d'utiliser l’effet T1 des SPIO pour caractériser la microcirculation placentaire par f=159,4 ml/min/100ml (+/- 54,6) et Vb =39,2% (+/- 11,9) pour 31 placentas « normaux ». En cas de RCIU, f diminue significativement pour les 23 placentas étudiés (f= 108,1 ml/min/100ml +/- 41, p=0,004), alors que la fraction volumique placentaire n'est pas modifiée (Vb=42,8% +/- 16,7, p=0,24). L’ASL nous a permis d’estimer la perfusion placentaire pour 47 placentas en condition physiologique, avec une perfusion estimée à 146,8 ml/min/100g (+/- 70,1).Chez l’Homme, 14 placentas ont été étudiés avec une perfusion placentaire globale estimée à 183 ml/min/100ml (+/-144) et nous avons également mis en évidence deux types de cinétique de rehaussement placentaire (précoce et intense et plus tardif et moins intense). La pharmacocinétique nous a permis d'étudier quantitativement le passage du chélate de gadolinium chez le fœtus. Ce passage est faible: par rapport à la concentration initiale du Dotarem®, la concentration sanguine fœtale correspond à 18,1x10-6 %, la concentration dans le liquide amniotique à 242,8 x10-6 % et 0,3 % de la dose initiale de Dotarem® est présente dans le placenta environ 70 heures après l’injection.Conclusion : Ce travail illustre la variété des techniques d'IRM fonctionnelle disponibles pour l'étude du placenta. La perfusion placentaire peut être quantifiée en DCE avec un agent particulaire à base de fer (SPIO) ou sans injection de produit de contraste en ASL chez le rat. L’étude de la perfusion placentaire chez l'Homme est possible en DCE avec les chélates de gadolinium.Mots clés : IRM, DCE, chélates de Gadolinium, ASL, perfusion placentaire, grossesse, placenta, retard de croissance intra-utérin. / Placental insufficiency is a serious medical condition with a diagnosis made usually too late to prevent introduction of effective therapies. The aim of this thesis is to develop, in pregnant rats and translate to humans, functional MRI (fMRI) tools allowing quantification of placental perfusion in clinical practice.Materials and Methods: Three studies using fMRI are part of this thesis. The first two were performed on a murine model. A dynamic sequence with injection of a contrast agent (DCE) has been developed with an iron oxide particle (SPIO) in a surgical model of chronic placental hypoperfusion with placental perfusion measurement (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. Another technique of fMRI was developed with Arterial Spin Labeling (ASL) to estimate placental perfusion in ml / min / 100g without injection of contrast media.The latest study was a translational research. It consisted in the development of a dynamic sequence with injection of gadolinium chelate, in order to obtain perfusion (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. We also studied maternal and fetal pharmacokinetics of gadolinium chelate.Results: In animals with SPIO DCE, our study allowed us to show that it is possible to use the T1 effect of SPIO to characterize the placental microcirculation by f = 159.4 ml / min / 100ml (+ / - 54.6) and Vb = 39.2% (11.9 +/-) for 31 « normal » placentas. In case of IUGR, f decreases significantly for the 23 examined placentas (f = 108.1 ml / min / 100ml +/- 41, p = 0.004), whereas the volume fraction placenta is not modified (Vb = 42 +/- 16.7 8 %, p = 0.24). ASL has allowed us to estimate placental perfusion for 47 placentas under physiological conditions, with an estimated perfusion of 146.8 ml / min / 100 g (70.1 +/-).In humans, 14 placentas were studied with an estimated perfusion of 183 ml / min / 100ml (+/- 144) and we also identified two types of placental kinetic enhancement (early and intense and later and less intense). Pharmacokinetics have allowed us to study quantitatively the transfer of gadolinium chelate in the fetus. This transfer is low compared to the initial concentration of Dotarem® : fetal blood concentration is 18.1x10-6%, concentration in amniotic fluid is 242.8 x10-6 % and 0.3% of the Dotarem® initial dose is present in the placenta approximately 70 hours after injection.Conclusion: This study illustrates the variety of functional MRI techniques available for placental study. Placental perfusion can be quantified by DCE with an iron oxide particle (SPIO) or without injection of contrast in ASL, in a rat model. The study of placental perfusion in humans is also possible in DCE with gadolinium chelates.

Cerebral small vessel disease (SVD) is a common cause of strokes and dementia. The pathogenesis of SVD is poorly understood, but imaging and biochemical investigations suggest that subtle blood-brain barrier (BBB) leakage may contribute to tissue damage. The most widely-used imaging method for assessing BBB integrity and other microvascular properties is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI has primarily been applied in situations where contrast uptake in tissue is typically large and rapid (e.g. neuro-oncology); the optimal approach for quantifying BBB integrity in diseases where the BBB remains largely intact and the reliability of resulting measurements is unclear. The main purpose of this thesis was to assess and improve the reliability of quantitative assessment of subtle BBB disruption, in order to illuminate its potential role in cerebral SVD. Firstly, a systematic literature review was performed in order to provide an overview of DCE-MRI methods in the brain. This review found large variations in MRI procedures and data analysis methods, resulting in widely varying estimates of tracer kinetic parameters. Secondly, this thesis focused on the analysis of DCE-MRI data acquired in an on-site clinical study of mild stroke patients. After performing basic DCE-MRI processing (e.g. selection of a vascular input function), this work aimed to determine the tracer kinetic modelling approach most suitable for assessing subtle BBB disruption in this cohort. Using data-driven model selection and computer simulations, the Patlak model was found to provide accurate estimates of blood plasma volume and low-level BBB leakage. Thirdly, this thesis aimed to investigate two potential pitfalls in the quantification of subtle BBB disruption. Contrast-free measurements in healthy volunteers revealed that a signal drift of approximately 0.1 %/min occurs during the DCE-MRI acquisition; computer simulations showed that this drift introduces significant systematic errors when estimating low-level tracer kinetic parameters. Furthermore, tracer kinetic analysis was performed in an external patient cohort in order to investigate the inter-study comparability of DCE-MRI measurements. Due to the nature of the acquisition protocol it proved difficult to obtain reliable estimates of BBB leakage, highlighting the importance of study design. Lastly, this thesis examined the relationship between quantitative MRI parameters and clinical measurements in cerebral SVD, with a focus on the estimates of blood volume and BBB leakage obtained in the internal SVD patient cohort. This work did not provide evidence that BBB leakage in normal-appearing tissue increases with SVD burden or predicts disease progression; however, increased BBB leakage was found in white matter hyperintensities. Furthermore, this work raises the possibility of a role for blood plasma volume and dietary salt intake in cerebral SVD. The work described in this thesis has demonstrated that it is possible to estimate subtle BBB disruption using DCE-MRI, provided that the measurement and data analysis strategies are carefully optimised. However, absolute values of tracer kinetic parameters should be interpreted with caution, particularly when making comparisons between studies, and sources of error and their influence should be estimated where possible. The exact roles of BBB breakdown and other microvascular changes in SVD pathology remain to be defined; however, the work presented in this thesis contributes further insights and, together with technical advances, will facilitate improved study design in the future.

This thesis deals with processing of data obtained by DCE-MRI, which uses magnetic resonance to track the propagation of contrast agents in the blo- odstream. Patient is given a contrast agent and then a series of images of the target area is taken. The output is a set of image data and perfusion maps. Work employs segmentation method which uses graph cuts to interactively look for the tumor, and evaluates it according to its shape properties. Study of whole data sets is simplified by image fusion methods.

We have conducted a systematic search for finite homomorphic images of several permutation and monomial progenitors. We have found original symmetric presentations for several important groups such as the Mathieu sporadic simple groups, Suzuki simple group, unitary group, Janko group, simplectic groups, and projective special linear groups. We have also constructed, using the technique of double coset enumeration, the following groups, L_2(11), S(4,3):2, M11, and PGL(2,11). The isomorphism class of each of the finite images is also given.

Isotopic methods have been developed over the last 10 years as a method for determining chemical interactions of chlorinated solvents. These methods are especially promising for. This study attempts to employ and develop compound specific isotopic analyses of TCE and cDCE, along with chemical data, to characterize the degradation of TCE in a fractured bedrock aquifers. The Smithville site is a contaminated field site with extremely high levels of TCE contamination that is currently undergoing monitored remediation. From December 2008 until April 2010 extended samples were collected from the site to provide additional data analyses including isotopic data. The redox conditions at the site are anoxic to reducing, with sulfate reduction and methanogenesis as dominant terminal electron accepting processes. Redox data indicates that well electrochemical conditions are highly variable within the site, including areas near the source zone that not very reducing. Documented changes in groundwater conditions to much more reducing environments indicate that oxidation of organic matter is occurring at the Smithville site in select wells. Chemical analyses of TCE, DCE, VC, ethene and ethane are employed determine whether reductive dechlorination was occurring at the site. Results of field testing indicate that many wells on site, especially in the proximity of the source zone, dechlorination products were found. The isotopic data had a high range in both carbon and chlorine isotopes. Chlorine isotopic data ranges from a δ37Cl(TCE) of 1.39 to 4.69, a δ37Cl(cDCE) of 3.57 to 13.86, a δ13C(TCE) of -28.9 to -20.7, and a δ13C(cDCE) of -26.5 to -11.82. The range in values indicate varying degrees of degradation throughout the site, with the same wells grouping together. Combined chemical, redox and isotopic data shows that degradation seems to be a removal process for TCE at the Smithville site. Concentrations of chemicals created as a result of TCE degradation verify degradation, especially in wells 15S9, R7 and 17S9. Historically production of DCE in significant amounts, above 1.0 ppb, was observed to only occur after 2003. In addition to this, DCE data shows that the percentage of DCE made up of cDCE is above 96%. This indicates that microbes most likely mediate the processes that formed DCE from TCE. The linear regression of the delta-delta plot for isotopic TCE data shows line that is likely a direct function of the carbon and chlorine isotopic fractionation imparted upon the original TCE released. The slope found is consistent with data collected from other studies though cannot be applied to determining the process directly given the range of variability in isotopic field data.