Termovizní zobrazování i 3D skenování jsou v současné době rychle se rozvíjející technologie. Obě technologie mají mnoho výhod, které by mohly být užitečné v medicíně. Jejich datová fúze přináší ještě více nových diagnostických informací, než kdyby byly použity samostatně. Cílem této práce je vývoj multispektrálního 3D skenovacího systému založeného na novém způsobu snímání pomocí robotického manipulátoru vybaveného laserovým snímačem, teplotní kamerou a barevnou kamerou. Navržené řešení přináší jak flexibilitu, tak přesnost. Tento systém skenování je dále využit v klinických aplikacích, aby byly ověřeny jeho schopnosti a ukázány přínosy nad rámec současného stavu techniky.

Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer’s disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

<div> <div> <div> <p>Recent observations of short-term changes in the neural health of youth athletes participating in collision sports such as football (boys) and soccer (girls) have incited a need to explore structural alterations in their brain tissue volumes. Studies have shown biochemical, vascular, functional connectivity, and white matter diffusivity changes in the brain physiology of these athletes that are strongly correlated with repetitive head acceleration exposure from on-field collisions. Here, research is presented that highlights regional anatomical volumetric measures that change longitudinally with accrued repetitive head impacts. A novel pipeline is introduced that provides simplified data analysis on a standard-space template to quantify group-level longitudinal volumetric changes within these populations. For both sports, results highlight incremental relative regional volumetric changes in the sub-cortical cerebrospinal fluid that are strongly correlated with head exposure events greater than a 50G threshold at the short-term post-season assessment. Moreover, longitudinal regional gray matter volumes are observed to decrease with time, only returning to baseline/pre-participation levels after sufficient (5-6 months) rest from collision-based exposure. These temporal structural volumetric alterations are significantly different from normal aging observed in gender and age-matched controls participating in non-collision sports. Future work involves modeling safe repetitive head exposure thresholds with multimodal image analysis and understanding their underlying physiological functioning. A possible pathophysiological pathway is presented highlighting the probable metabolic regulatory mechanisms. The interdisciplinary nature of this work is crucial to understand this pathology accurately and aid healthcare, sport professionals in the future. It is evident that continual participation in collision- based activities may represent a risk wherein recovery cannot occur. Even when present, the degree of the eventual recovery remains to be explored but has strong implications for the well-being of collision-sport participants. </p> </div> </div> </div>

Despite decades of research of normal pressure hydrocephalus (NPH), a clear pathophysiological mechanism of the disease is sill unknown. This results in the absence of a unambiguous diagnostic biomarker. Moreover, NPH in contrast to similar neurodegenerative diseases is curable by insertion of a ventrikulo-peritoneal shunt. Now the diagnostics is based on invasive functional testing, on the contrary, imaging methods play only a supporting role. This work is processed with an effort to find a sufficiently sensitive and specific biomarker of MRI imaging using advanced analytical methods. For this reason, the structural volumetry and the phase contrast method were tested. The individual partial results of both of these modalities have already been described in the literature, but the conclusions were controversial. The main contribution of this work is the range of tested parameters and their to date untested advanced analysis - accurate automatic segmentation in volumetric study and machine learning algorithms in phase contrast study. In a volumetric study, we segmented a total of 26 structures in 74 patients (29 with diagnosed NPH, 45 without NPH). In the case of preoperative examination, we demonstrated statistically significant differences in the size of the left hippocampus, corpus callosum, left...

Einleitung: Französische Bulldoggen (FBD) werden beinahe täglich zur weiteren Abklärung intrakranieller Erkrankungen in der Klinik für Kleintiere der Universität Leipzig vorgestellt. Die während der Magnetresonanztomographie (MRT) des Gehirns häufig beobachtete subjektive Ventrikulomegalie der Seitenventrikel (SV) wirft die Frage auf, ob es sich hierbei um einen rassespezifischen Normalbefund oder einen Befund mit pathologischem Charakter handelt. Ziele der Untersuchung: Ziel war die Messung der Volumina der SV neurologisch unauffälliger FBD sowie der Vergleich dieser Werte mit denen des Dackels als mesozephaler Referenzrasse mit einer ähnlichen Körpermasse. Darüber hinaus wurde der Einfluss von Gewicht, Geschlecht, Kastrationsstatus und Alter der Tiere auf die Volumina untersucht. Die Häufigkeit optisch wahrnehmbarer ventrikulärer Asymmetrien für beide Rassen sowie deren Seitenverteilung wurde erfasst und die Grenze für die optische Wahrnehmung einer Asymmetrie ermittelt. Tiere, Material und Methoden: Insgesamt wurden vierzig FBD und fünfzehn Dackel prospektiv in die Studie aufgenommen. Auf der Basis eines Besitzerfragebogens zu neurologischen Symptomen (Verhalten des Tieres, Koordinationsstörungen, epileptische Anfälle) und einer klinischen neurologischen Untersuchung wurden die Tiere als neurologisch unauffällig hinsichtlich intrakranieller Erkrankungen eingestuft. Von jedem Tier wurden T1-gewichtete MRT-Aufnahmen des Gehirns in transversaler Schnittebene (Schichtdicke 2,0 mm) angefertigt. Zufallsbefunde in der MRT-Untersuchung, welche die Morphologie des Gehirnparenchyms, die Liquorzusammensetzung oder den Liquorfluss beeinflussen könnten, führten zum Ausschluss der Tiere. Die SV der Hunde wurden über die Software ITK-SNAP manuell segmentiert und volumetrisch vermessen. Zusätzlich wurden die SV rein optisch hinsichtlich vorliegender Asymmetrien beurteilt. Im positiven Fall wurde die größere Seite dokumentiert. Die Analyse der Bilddaten wurde einmalig durch die über Erfahrung in der manuellen Segmentation verfügende Autorin (JD) selbst durchgeführt. Die ermittelten Daten beider Rassen wurden durch mehrere Medianvergleichstests auf signifikante Unterschiede geprüft (Wilcoxon-Mann-Whitney-Test, χ² – Test, Kruskal-Wallis-Test, van der Waerden-Test). Der Einfluss von Geschlecht, Kastrationsstatus, Alter und Gewicht der Tiere auf das Seitenventrikelvolumen wurden mit einer linearen Regressionsanalyse überprüft. Die Durchführung dieser Studie fand Zustimmung durch die Ethikkommission der Veterinärmedizinischen Fakultät der Universität Leipzig. Ergebnisse: Das Volumen der SV der FBD belief sich im Median auf 786 mm³ (linker SV = 380 mm³; rechter SV = 413 mm³). Das Volumen der SV der Dackel lag im Median bei 1141 mm³ (linker SV = 589 mm³; rechter SV = 619 mm³). Der Unterschied der Volumina zwischen den Rassen war, unabhängig vom gewählten Testverfahren, statistisch nicht signifikant. Alter (p = 0,28), Geschlecht (p = 0,39), Kastrationsstatus (p = 0,09) und Gewicht (p = 0,60) der Tiere hatten keinen statistisch signifikanten Einfluss auf das Gesamtvolumen der SV. Asymmetrien der SV lagen bei 50 % der FBD und 60 % der Dackel vor, wobei in 50 % (FBD) bzw. 66,7 % (Dackel) dieser Fälle der linke SV vergrößert war. Die Seitenverteilung des größeren Ventrikels bei vorliegender Asymmetrie hatte sowohl für die FBD (p = 0,83) und den Dackel (p = 0,35) keine statistische Signifikanz. Asymmetrien zwischen den beiden SV konnten ab einem prozentualen Volumenunterschied von 22 % sicher optisch von der Untersucherin (JD) in den MRT-Aufnahmen erkannt werden. Schlussfolgerung: Die Vermutung, dass FBD zu einem erhöhten Volumen der SV und damit physiologisch zu Ventrikulomegalien neigen, konnte nicht bestätigt werden. Die untersuchten Tiere zeigten deskriptiv sogar geringere Volumina als die zum Vergleich gewählten Dackel und die in der Literatur verfügbaren Daten anderer Hunderassen. Das Vorliegen vergrößerter SV sollte daher nicht als anatomische Normvariante gewertet und bis zum Beweis des Gegenteils als pathologisch betrachtet werden. Asymmetrien der SV treten dagegen, wie auch bei anderen Hunderassen, bei neurologisch unauffälligen FBD in annähernd der Hälfte der Tiere auf. / Introduction: French Bulldogs (FB) are presented to our clinic almost daily for diagnostic workup and therapy of intracranial disorders. Subjective lateral ventriculomegaly is frequently observed on diagnostic imaging of these dogs. This raises the question whether this is a breed-specific normal finding or a finding with pathological character. Objective: To measure the volume of the lateral ventricles (LV) of neurologically unremarkable FB and compare these values with those of a mesocephalic breed of nearly the same weight (Dachshunds). The influence of body weight, sex, neutering status and age was investigated. Additionally, ventricular asymmetry was assessed and, if present, the enlarged side was documented. The threshold of subjective detection of asymmetric ventricles was calculated. Animals, material and methods: Forty FB and fifteen Dachshunds were included in this study prospectively. Animals were classified as healthy regarding intracranial disease via an owner questionnaire about neurological symptoms of the animal (behaviour of the animal, deficits in coordination, potential epileptic seizures) and a complete neurological examination. Transversal, T1-weighted MRI brain images with a slice thickness of 2,0 mm were obtained of each animal. Incidental findings on diagnostic imaging which could influence the morphology of brain parenchyma and the circulation or composition of cerebrospinal fluid lead to exclusion of the animals. LV were segmented manually and quantitative volumetric measurements were obtained using the open-source software ITK-SNAP. Assessment of lateral ventricular asymmetry and, if present, of the enlarged side was also done in this software. These steps were performed once by the author (JD) of this study, who already had experience using this software for manual image segmentation. Volumetric data of both breeds were checked for significant differences of medians by several statistical tests (Wilcoxon-Mann-Whitney-test, χ² – test, Kruskal-Wallis-test, van der Waerden-test). The influence of sex, neutering status, age and body weight on the LV volume was verified via a linear regression analysis. The Ethics Commitee of the Faculty of Veterinary Medicine, University of Leipzig, approved the concept and execution of this study. Results: Total median LV volume of the FB was 786 mm³ (left LV = 380 mm³; right LV = 413 mm³). For the Dachshunds, median volumes were 1141 mm³ in total and 589 mm³ (left LV) and 619 mm³ (right LV) respectively. There was no statistic significant difference of LV volume between the breeds, independent of the statistical test used. Age (p = 0,28), sex (p = 0,39), neutering status (p = 0,09) and body weight (p = 0,60) had no statistically significant influence on LV volume as well. 50 % of FB and 60 % of the Dachshunds had a LV asymmetry. The incidence of ventricular asymmetry was statistically significant in both breeds (p < 0,001). The LV was larger than the right in 50 % of FB and 66,7 % of Dachshunds. This finding was not statistically significant (p = 0,83 in FB and 0,35 in Dachshunds). A percentage difference in volume of 22 % between the lateral ventricles was determined as threshold value for visual detection of asymmetries. Conclusion: The assumption of a higher volume of the LV and therefore physiological ventriculomegaly in the FB breed could not be confirmed. Furthermore, the FB in this study had lower volumes of the LV compared to the values of Dachshunds and available data of other breeds in veterinary literature. Therefore, ventriculomegaly should not be considered as a normal anatomic variant in this breed and instead be considered as pathological, leading to further diagnostic workup. In contrast, lateral ventricular asymmetry seems to be a common incidental finding in neurologically normal FB as well as in other dog breeds.

Les résultats présentés dans cette thèse précisent certains aspects de la fonction du cotransporteur Na+/glucose (SGLT1), une protéine transmembranaire qui utilise le gradient électrochimique favorable des ions Na+ afin d’accumuler le glucose à l’intérieur des cellules épithéliales de l’intestin grêle et du rein. Nous avons tout d’abord utilisé l’électrophysiologie à deux microélectrodes sur des ovocytes de xénope afin d’identifier les ions qui constituaient le courant de fuite de SGLT1, un courant mesuré en absence de glucose qui est découplé de la stoechiométrie stricte de 2 Na+/1 glucose caractérisant le cotransport. Nos résultats ont démontré que des cations comme le Li+, le K+ et le Cs+, qui n’interagissent que faiblement avec les sites de liaison de SGLT1 et ne permettent pas les conformations engendrées par la liaison du Na+, pouvaient néanmoins générer un courant de fuite d’amplitude comparable à celui mesuré en présence de Na+. Ceci suggère que le courant de fuite traverse SGLT1 en utilisant une voie de perméation différente de celle définie par les changements de conformation propres au cotransport Na+/glucose, possiblement similaire à celle empruntée par la perméabilité à l’eau passive. Dans un deuxième temps, nous avons cherché à estimer la vitesse des cycles de cotransport de SGLT1 à l’aide de la technique de la trappe ionique, selon laquelle le large bout d’une électrode sélective (~100 μm) est pressé contre la membrane plasmique d’un ovocyte et circonscrit ainsi un petit volume de solution extracellulaire que l’on nomme la trappe. Les variations de concentration ionique se produisant dans la trappe en conséquence de l’activité de SGLT1 nous ont permis de déduire que le cotransport Na+/glucose s’effectuait à un rythme d’environ 13 s-1 lorsque le potentiel membranaire était fixé à -155 mV. Suite à cela, nous nous sommes intéressés au développement d’un modèle cinétique de SGLT1. En se servant de l’algorithme du recuit simulé, nous avons construit un schéma cinétique à 7 états reproduisant de façon précise les courants du cotransporteur en fonction du Na+ et du glucose extracellulaire. Notre modèle prédit qu’en présence d’une concentration saturante de glucose, la réorientation dans la membrane de SGLT1 suivant le relâchement intracellulaire de ses substrats est l’étape qui limite la vitesse de cotransport. / The results presented in this thesis clarify certain functional aspects of the Na+/glucose cotransporter (SGLT1), a membrane protein which uses the downhill electrochemical gradient of Na+ ions to drive the accumulation of glucose in epithelial cells of the small intestine and the kidney. We first used two microelectrodes electrophysiology on Xenopus oocytes to indentify the ionic species mediating the leak current of SGLT1, a current measured in the absence of glucose that is uncoupled from the strict 2 Na+/1 glucose stoichiometry characterising cotransport. Our results showed that cations such as Li+, K+ and Cs+, which interact weakly with SGLT1 binding sites and are unable to generate the conformational changes that are triggered by Na+ binding, were however able to generate leak currents similar in amplitude to the one measured in the presence of Na+. This suggests that the leak current permeating through SGLT1 does so using a pathway that differs from the conformational changes associated with Na+/glucose cotransport. Moreover, it was found that the cationic leak and the passive water permeability could share a common pathway. We then sought to estimate the turnover rate of SGLT1 using the ion-trap technique, where a large tip ion-selective electrode (~100 μm) is pushed against the oocyte plasma membrane, thus enclosing a small volume of extracellular solution referred to as the trap. The variations in ionic concentration occurring in the trap as a consequence of SGLT1 activity made it possible to assess that the turnover rate of Na+/glucose cotransport was 13 s-1 when the membrane potential was clamped to -155 mV. As a last project, we focused our interest on the development of a kinetic model for SGLT1. Taking advantage of the simulated annealing algorithm, we constructed a 7-state kinetic scheme whose predictions accurately reproduced the currents of the cotransporter as a function of extracellular Na+ and glucose. According to our model, the rate limiting step of cotransport under a saturating glucose concentration is the reorientation of the empty carrier that follows the intracellular release of substrates.

Le foie est un organe vital ayant une capacité de régénération exceptionnelle et un rôle crucial dans le fonctionnement de l’organisme. L’évaluation du volume du foie est un outil important pouvant être utilisé comme marqueur biologique de sévérité de maladies hépatiques. La volumétrie du foie est indiquée avant les hépatectomies majeures, l’embolisation de la veine porte et la transplantation. La méthode la plus répandue sur la base d'examens de tomodensitométrie (TDM) et d'imagerie par résonance magnétique (IRM) consiste à délimiter le contour du foie sur plusieurs coupes consécutives, un processus appelé la «segmentation». Nous présentons la conception et la stratégie de validation pour une méthode de segmentation semi-automatisée développée à notre institution. Notre méthode représente une approche basée sur un modèle utilisant l’interpolation variationnelle de forme ainsi que l’optimisation de maillages de Laplace. La méthode a été conçue afin d’être compatible avec la TDM ainsi que l' IRM. Nous avons évalué la répétabilité, la fiabilité ainsi que l’efficacité de notre méthode semi-automatisée de segmentation avec deux études transversales conçues rétrospectivement. Les résultats de nos études de validation suggèrent que la méthode de segmentation confère une fiabilité et répétabilité comparables à la segmentation manuelle. De plus, cette méthode diminue de façon significative le temps d’interaction, la rendant ainsi adaptée à la pratique clinique courante. D’autres études pourraient incorporer la volumétrie afin de déterminer des marqueurs biologiques de maladie hépatique basés sur le volume tels que la présence de stéatose, de fer, ou encore la mesure de fibrose par unité de volume. / The liver is a vital abdominal organ known for its remarkable regenerative capacity and fundamental role in organism viability. Assessment of liver volume is an important tool which physicians use as a biomarker of disease severity. Liver volumetry is clinically indicated prior to major hepatectomy, portal vein embolization and transplantation. The most popular method to determine liver volume from computed tomography (CT) and magnetic resonance imaging (MRI) examinations involves contouring the liver on consecutive imaging slices, a process called “segmentation”. Segmentation can be performed either manually or in an automated fashion. We present the design concept and validation strategy for an innovative semiautomated liver segmentation method developed at our institution. Our method represents a model-based approach using variational shape interpolation and Laplacian mesh optimization techniques. It is independent of training data, requires limited user interactions and is robust to a variety of pathological cases. Further, it was designed for compatibility with both CT and MRI examinations. We evaluated the repeatability, agreement and efficiency of our semiautomated method in two retrospective cross-sectional studies. The results of our validation studies suggest that semiautomated liver segmentation can provide strong agreement and repeatability when compared to manual segmentation. Further, segmentation automation significantly shortens interaction time, thus making it suitable for daily clinical practice. Future studies may incorporate liver volumetry to determine volume-averaged biomarkers of liver disease, such as such as fat, iron or fibrosis measurements per unit volume. Segmental volumetry could also be assessed based on subsegmentation of vascular anatomy.

Racional: A epilepsia do lobo temporal está comumente associada à farmacorresistência e tem a esclerose hipocampal como achado neuropatológico em mais da metade dos casos. Histologicamente, a esclerose hipocampal está associada à perda neuronal diferencial e gliose, além de alterações nos níveis de moléculas associadas à homeostase da água tecidual, como a aquaporina 4 e a molécula de matriz sulfato de condroitina. Em imagens de ressonância nuclear magnética, a esclerose é caracterizada por redução de volume em sequências ponderadas em T1, aumento de sinal e tempo de relaxamento em sequências ponderadas em T2 e redução na transferência de magnetização. Justificativa e Objetivos: Uma vez que tanto o sinal T2 quando a transferência de magnetização são dependentes da água tecidual, nosso objetivo é avaliar, na formação hipocampal de pacientes com epilepsia do lobo temporal, as correlações entre populações celulares e moléculas ligadas à homeostase da água e as imagens ponderadas em T2 e transferência de magnetização. Visamos ainda definir, na formação hipocampal de indivíduos sem alterações neuropatológicas, o volume de cada um dos subcampos hipocampais. Metodologia: Pacientes com epilepsia do lobo temporal farmacorresistente (ELT, n = 43), bem como voluntários sadios (controle radiológico, CH, n = 20), foram submetidos a exames de ressonância magnética em máquina de 3T para mensuração da volumetria hipocampal, tempo de relaxamento T2 e transferência de magnetização hipocampal (exames in vivo). Após o tratamento cirúrgico para o controle das crises, os hipocampos dos pacientes com ELT foram fixados por 8 dias e submetidos aos exames ex vivo em máquina de 3T para cálculo do tempo de relaxamento T2 de cada subcampo hipocampal. Hipocampos controle (Controle historadiológico, CHR, n = 14), foram obtidos de autópsias de pacientes sem histórico ante-mortem de doença neurológica ou presença de patologia no exame do encéfalo pos mortem. Ambos os grupos controle foram pareados para idade em relação ao grupo ELT. Alguns dos casos CHR (n = 6) foram também submetidos à imagem 3D T2 em máquina de 4,7T para cálculo de volumetria dos subcampos hipocampais. Após emblocamento em parafina, secções coronais hipocampais dos casos CHR e ELT foram submetidas às técnicas de histoquímica básica Hematoxilina e Eosina e Luxol Fast Blue, e às imuno-histoquímicas para avaliação das populações neuronais (NeuN), astrócitos reativos (GFAP), micróglias ativadas (HLA-DR) e para a expressão de aquaporina 4 (AQP4) e níveis de sulfato de condroitina (CS-56). Para a comparação entre os grupos, foram realizados testes t para dados paramétricos e Mann-Whitney para dados não-paramétricos. Testes de correlação foram empregados para análise da associação entre as avaliações histológicas e os exames de ressonância magnética. Resultados: Pacientes com ELT apresentaram menor volume hipocampal, maior tempo de relaxamento T2 e menor transferência de magnetização no exame in vivo, quando comparados com o CR. O exame ex vivo para a volumetria dos subcampos hipocampais em casos do grupo CHR indicou que a fascia dentata, a região CA1 e o subículo correspondem à 85 % do volume hipocampal total. Quanto ao tempo de relaxamento T2 ex vivo, foi observado aumento em todos os subcampos hipocampais do grupo ELT, à exceção da fascia dentata, quando comparados ao CHR. A avaliação da densidade neuronal indicou redução significativa em todos os subcampos dos casos ELT, à exceção do subículo, quando comparados ao CHR. Em relação aos valores do grupo CHR, foi observada astrogliose em quase todos subcampos da formação hipocampal (a exceção da zona subgranular e do hilo) e microgliose em todos os subcampos (exceto pelo subículo) dos casos com ELT. Pacientes com ELT apresentaram redução na expressão de aquaporina 4 perivascular em todos os subcampos do hipocampo, comparados ao CHR. Aumento nos níveis de sulfato de condroitina foi observado em todos os subcampos da formação hipocampal, à exceção da camada granular, nos pacientes com ELT. O volume hipocampal e a transferência de magnetização in vivo dos pacientes com ELT correlacionaram-se tanto com a população neuronal como com os níveis de sulfato de condroitina, enquanto que o tempo de relaxamento in vivo correlacionou-se com a população astroglial e os níveis de sulfato de condroitina. O exame ex vivo corroborou a correlação entre a população glial e o tempo de relaxamento observado nos pacientes com ELT. A diferença entre o tempo de relaxamento in vivo e ex vivo correlacionou-se tanto com a difusibilidade da água no tecido como com os níveis de sulfato de condroitina. Conclusões: Nossos dados indicam correlação entre a patologia hipocampal e as imagens de ressonância nuclear magnética, sendo que a maior qualidade das imagens ex vivo permitiu uma avaliação mais direta entre o sinal de ressonância e a patologia, indicando importância da população celular e matriz extracelular para o volume hipocampal e a transferência de magnetização, e da astrogliose para o tempo de relaxamento T2. Finalmente, nossos dados mostraram que CA1, subículo e fascia dentata tem grande participação no volume hipocampal, sendo que alterações nestas regiões tem um papel mais relevante nas alterações observadas na ressonância magnética, como indicado por nossas correlações. / Rationale: Drug resistant temporal lobe epilepsy is often associated with hippocampal sclerosis. Histological evaluation reveals differential neuronal loss, gliosis and changes in molecules associated with water homeostasis, such as aquaporin 4 and chondroitin sulfate. Magnetic resonance imaging in these cases often reveals hippocampal atrophy, increased T2 signal and T2 relaxation and reduced magnetization transfer ratio in the hippocampus. Aims: Once both T2 signal and magnetization transfer are affected by tissue water, our goal was to evaluate, in the hippocampus of drug-resistant temporal lobe epilepsy patients who underwent surgery for seizure control, the associations between cellular populations, aquaporin 4 and chondroitin sulfate with T2 relaxation time and magnetization transfer. Additionally, we intended to measure the individual volume of each hippocampal subfield in hippocampus from patients without neurological disease. Methods: Patients with drug-resistant temporal lobe epilepsy (TLE, n = 43) and age-matched health volunteers (radiological control, RC, n = 20) were submitted to magnetic resonance in a 3T machine for hippocampal volumetry measure, T2 relaxation and magnetization transfer (in vivo examination). After surgical treatment for seizure control, hippocampi from the TLE patients were fixed in formalin for 8 days and then submitted to ex vivo imaging in 3T for relaxation time of every hippocampal subfield. Control hippocampi were obtained from autopsies of age-matched patients without ante mortem history of neurological disease or post mortem neurological pathology, and underwent the same ex vivo imaging (histo-radiological control, HRC, n = 14). Six cases from the HRC underwent 3D T2 imaging in a 4.7T machine, in order to measure the volumes of the hippocampal subfields. Paraffin embedded hippocampal sections from TLE and HRC were submitted to Hematoxilin-Eosin and Luxol Fast Blue histochemistries, and to immunohistochemistries for the evaluation of neurons (NeuN), reactive astrocytes (GFAP), activated microglia (HLA-DR), for aquaporin 4 (AQP4) and for chondroitin sulfate (CS-56). Students t-test or Mann-Whitneys test were performed for comparison between groups, and correlation tests were performed for the comparison between histological and magnetic resonance measures. Results: Patients with TLE presented reduced hippocampal volume, increased T2 relaxation time and reduced magnetization transfer, when compared to RC. The ex vivo volumetry of the hippocampal subfields revealed that fascia dentata, CA1 and subiculum together correspond to 85 % of the total hippocampal volume. Ex vivo relaxation time, as the in vivo, were increased in the subfields of TLE patients, when compared to HRC. Compared to HRC, TLE patients presented neuron loss and microgliosis in all hippocampal subfields but the subiculum, and astrogliosis in all hippocampal subfields but the subgranule zone and the hilus. Reduced perivascular aquaporin 4 was observed in all hippocampal subfields of TLE patients, and increased chondroitin sulfate was observed in all hippocampal subfields, with the exception of granule cell layer, of TLE patients, when compared to HRC. In TLE, both in vivo hippocampal volume and magnetization transfer correlated with the levels of chondroitin sulfate and the neuronal population, whereas the in vivo relaxation time correlated with the astroglial population and the levels of chondroitin sulfate. Ex vivo relaxation time also correlated with the astroglial population in TLE patients. The difference between in vivo and ex vivo relaxation values correlated with water difusibility and the levels of chondroitin sulfate. Conclusion: Our data indicate the importance of neuron population and extracellular matrix to both hippocampal volume and magnetization transfer, and of the reactive astrocytes for T2 relaxation. Ex vivo relaxation time allowed a more detailed evaluation, and indicated more robust correlations between reactive astrocytes and T2 relaxation. Finally, Our data indicated that CA1, the subiculum and fascia dentata are the major contributors to hippocampal volume, so changes in these subfields most likely will affect magnetic resonance imaging.

Em ultimas décadas, a conversão de alcanos leves em suas correspondentes olefinas tem sido objeto de intensas pesquisas, impulsionadas inclusive pelo aumento crescente da demanda do propileno como um importante produto petroquímico. A desidrogenação oxidativa (ODH) do propano representa uma via alternativa promissor para a produção de propeno, ao apresentar-se como uma reação exotérmica e não limitada termodinamicamente. Diferentes óxidos suportados ou mistos têm sido desenvolvidos com a finalidade de aumentar a atividade e seletividade em relação as olefinas. Metais alcalinos são importantes agentes promotores que proporcionam uma melhor seletividade as olefinas devido a redução da acidez e aumento da basicidade da superfície do catalisador. A proposta deste presente trabalho foi desenvolver metodologias de síntese de catalisadores de oxido de vanádio suportado em aluminas de diferentes fases cristalinas e dopados com sódio ou potássio a fim de avalia-los em testes catalíticos de desidrogenação oxidativa do propano. Para tanto, foram utilizadas as seguintes técnicas de caracterização: volumetria N2, difratometria de raios X (DRX) e redução a temperatura programada (RTP). As características acidas e/ou básicas dos suportes e catalisadores foram avaliadas pelas reações de decomposição de isopropanol. / In recent decades, the conversion of light alkanes to their corresponding olefins has been the subject of intense research, mainly driven by the increasing demand of propylene as an important petrochemical product. Oxidative dehydrogenation (ODH) propane is a promising alternative way to propylene production, which it is presented as an exothermic reaction and not limited thermodynamically. Different supported or mixed oxides have been developed in order to increase the activity and selectivity to olefins. Alkali metals are important promoters, which provide improved selectivity to olefins due to reduction of acidity and increasing basicity of the catalyst surface. The purpose of the present study was to develop synthesis methods of vanadium oxide catalysts supported on alumina of the different crystalline phases and doped with sodium or potassium in order to evaluate them in catalytic tests of propane oxidative dehydrogenation. For in such a way, the following characterization techniques were used: N2 volumetry, X-ray diffractometry (XRD) and temperature programmed reduction (TPR). The properties acid and/or basic of supports and catalysts were evaluated by the isopropanol decomposition reaction.