1981 entwickelten Gerd Binnig und Heinrich Rohrer bei IBM in Zürich das "Scanning Tunneling Microscope". Damit wurde erstmalig das lokal hochaufgelöste Erfassen (bis in den atomaren Auflösungsbereich) von Objekteigenschaften im Nahfeld inerter Oberflächen möglich. Dies und insbesondere die Weiterentwicklung der Technologie und die spätere (1986) Etablierung der Rasterkraftmikroskopie (Atomic Force Microscopy - AFM), die diese Auflösungsmöglichkeiten der Rastersondenmikroskope auch an Non-Konduktoren (nicht leitende Untersuchungsoberflächen) realisieren konnte, stellte die Geburtsstunde einer neuen mikroskopischen Ära auf dem Gebiet der biomedizinischen Grundlagenforschung dar (Kapitel 1.3). Das Studium der umfangreichen Literaturquellen zu diesem Thema und der direkte wissenschaftliche Kontakt und Erfahrungsaustausch mit anderen AFM- Arbeitsgruppen ließen im Initialstadium dieser vorliegenden Arbeit bereits erkennen, dass in der kardiovaskulären Grundlagenforschung zunehmend rasterkraftmikroskopische Versuchsansätze bearbeitet und kardiologisch interessante Fragestellungen mittels dieser Methode begleitend untersucht wurden (Kapitel 1.4). Das Ziel dieser vorliegenden Arbeit bestand darin, kardiovaskulär relevante Zellen und Einzelproteine in vivo und interventionelle Materialien (Stents) rasterkraftmikroskopisch zu untersuchen, wobei die Etablierung und technisch aufwendige Optimierung dieser neuen mikroskopischen (Kapitel 3.1) und der zellspezifisch präparatorischen Methoden (Kapitel 3.2) an diesen Untersuchungsobjekten im Mittelpunkt stehen sollte. Die im Rahmen dieser Arbeit untersuchten endothelialen Zellen und H9C2-Myozyten stammten aus, in unserem Forschungslabor etablierten, immortalen Kulturzelllinien. Die adulten und Kardiomyozyten neonataler Ratten, die kardial- fibrozytären Zellen sowie die Thrombozyten wurden primär isoliert und als Primärkulturzellen kultiviert (Kapitel 3.2.3 und 3.2.4). Außerdem wurden vitale aortale Endothelzellen unterschiedlicher Tiere (Ratte, Meerschwein, Kaninchen) im Gewebsverband der thorakalen Aorta untersucht (Kapitel 4.2). Die Zellen wurden initial, im Rahmen der Etablierungsphase mittels unterschiedlicher Methoden fixiert und nachfolgend rasterkraftmikroskopisch untersucht und dargestellt. Der Etablierungsprozess der Methodik begann mit der Abbildung luftgetrockneter Zellen (Kapitel 4.1.1) unter Raumbedingungen und setzte sich über verschiedene Modifikationen der Zellpräparation (z.B. Glutardialdehydfixation, Cryofixation), des Abbildungsmodus (Contact-, Non-Contact-, Tapping-Mode) und der Abbildungsbedingungen (Raumbedingungen, zellphysiologische Umgebung) fort, so dass schließlich die Abbildung vitaler Zellen (Kapitel 4.1.2 und Kapitel 4.2 - 4.5) in ihrer strukturellen und funktionellen Umgebung (z.B. aortale Endothelzellen im Gewebsverband) etabliert werden konnte und routinemäßig reproduzierbar war. An stabilen oder künstlich stabilisierten Strukturen der o.g. vitalen Zellen wurden erste orientierende Messungen der bioelastischen Eigenschaften (Kraft-Abstands-Kurven, Kapitel 4.1.2.1) durchgeführt. Außerdem haben wir im Einzelfall, wenn technisch und apparativ möglich, andere hochauflösende strukturanalytische Verfahren (z.B. TEM) als mikroskopische Referenzuntersuchungen herangezogen (Kapitel 4.1.2; 4.4.1; 4.6), wobei z.T. erstaunliche Übereinstimmung zwischen den AFM- Daten und den strukturanalytischen Daten der Referenzmethoden nachweisbar waren. Ein strukturell durch Elektronenmikroskopie und Röntgendiffraktionsanalyse sehr gut beschriebenes komplexes Funktionsprotein, das 20-S-Proteasom, wurde mittels der Rasterkraftmikroskopie abgebildet und vermessen und die so gewonnenen strukturanalytischen Daten mit den bekannten strukturellen Abmessungen des Proteins verglichen (Kapitel 4.6). Die hierbei detektierten dimensionalen Abweichungen zwischen den AFM- assoziierten Daten und den bekannten strukturanalytischen Daten der Elektronenmikroskopie wurden im Kontext der funktionellen Integrität des Proteins und hinsichtlich möglicher methodischer Fehlereinflüsse (Kapitel 3.1.4.3) diskutiert. Interventionelle Materialien (Stents), die in der täglichen kardiologischen Praxis Anwendung finden, sind hinsichtlich ihrer Ultrastruktur mittels dieser hochsensitiven Abbildungsmethode im Nahfeld von Objektoberflächen untersucht worden. Bezüglich ihrer nativen Oberflächenbeschaffenheit und ihrer mechanischen Alteration durch den Ballon- Dilatationsprozess wurden die Stents sehr detailliert qualitativ und quantitativ (Kapitel 4.7) beschrieben, wobei Prädilektionsstellen der prozedural- assoziierten mechanischen Beanspruchung der Stents durch die hier beschriebene, oberflächensensitive AFM- Methode sehr genau diskriminiert werden konnten. Die präparierten Stents wurden weiterführend mit humanen Thrombozytenkonzentraten inkubiert und die Zell- Stentoberflächenkontakte sowie mögliche Stentoberflächen- induzierte Veränderungen der Thrombozyten sind morphologisch ausführlich beschrieben worden. Letztendlich wurde im Rahmen der vorliegenden Arbeit die spezifische Aktivierung der vitalen Thrombozyten durch pharmakologische Stimulantien (z.B. ADP) mit der, durch den AFM-Abbildungsprozess induzierten Thrombozytenaktivierung (Kapitel 4.5) unter AFM-Bedingungen verglichen und diskutiert. Die Ergebnisse dieser Arbeit weisen, dass mit der AFM-Technologie und objektorientiert optimierten Mess- und Präparationsmethoden ein neues mikroskopisches Analyseverfahren vorliegt, dass zum einen real-dreidimensionale morphologische Bildgebung bis in den submolekularen Auflösungsbereich an vitalen Zellen und präparierten Proteinkomplexen, zum anderen aber gleichermaßen Funktionsanalytik in Form von Messungen zelldynamischer Prozesse wie Migrationsbewegungen und Kontraktionen sowie visko- elastische Quantifizierung von Zellmembranen erlaubt. Der Vorteil gegenüber den meisten gegenwärtig verfügbaren mikroskopischen Methoden liegt in der neu eröffneten Möglichkeit der seriellen, wiederholten und stabil reproduzierbaren Messung an vitalen Zellen und zellulären Substrukturen. Insofern könnte in Zukunft diese neue Technologie eine methodische Bereicherung der mikroskopisch-morphologisch und funktionell orientierten Analysetechnik darstellen. / In 1981 Binnig and Rohrer invented the "Scanning Tunneling Microscope". Thereby it became feasible to high-resolution record the surface-properties of specimens (up to atomic resolution) at the nearfield of inert surfaces. This and in detail the further development of this technology and the establishment of "Atomic Force Microscopy" (1986), that allows implementation of this resolution capabilities in non-conductors or insulating materials represent the birth of a new microscopic era in the field of biomedical basic research (chapter 1.3). The promise of atomic (scanning) force microscopy (AFM) for cardiovascular research is enormous. The perusal of the extensive literature concerning this topic and scientific contact with other researchers reveals initial the capabilities of this method in cardiovascular basic research. Intriguing questions of cardiology may investigate concomitantly with help of scanning-force-micoscopic approaches (chapter 1.4). The aim of this study was to investigate relevant cardiovascular cells and single proteins in-vivo and specific materials (coronary artery stents) with scanning-force-micoscopic setup. The establishment and expensive optimization of this new microscopic method (chapter 3.1) and of the cell specific preparatory methods (chapter 3.2) represented the center of interest of our inevestigations. The endothelial cells and H9C2-myocytes stem from established imortal cell culture lines. The adult cardiomyocytes and cardiomyocytes of neonatal rats, the fibrocytes and the thrombocytes were primarily cultivated (chapter 3.2.3 and 3.2.4). In addition we investigated aortic endothelial cells of intact aortic tissue of different animals (rat, guinea pig, rabbit - chapter 4.2). During the establish experiments cells underlied different methods of cell-fixation. The primary investigations was performed using air-dried cells (chapter 4.1.1) analyzed in room ambient conditions and were continued by different modifications of cell-preparation. (e.g. glutardialdehyde-fixation, cryo-fixation), of microscopic mode (contact-, non-contact-, tapping-mode) and of cell-specific environmental conditions (from room ambient to cellphysiological medium and temperature). As result we became enabled to investigate (reproducible and routinely) vital cells (chapter 4.1.2 and chapter 4.2 - 4.5) embedded in physiological normal structural und functional ambient conditions (e.g. endothelial cells of intact aortic tisue in-vivo). Additionally, we performed measurements of bio-elastic properties of stable or artificial stabilized structures of named cells (force-distances-curves - chapter 4.1.2.1). If posibble, depending of available technical equipment, we compared our microscopic results with other high-resolution analytical procedures of reference (e.g. TEM - Kapitel 4.1.2; 4.4.1; 4.6) and detected astonishing congruence between the data. Furthermore we analyzed the well-described (electron-microscopy and x-ray-diffraction data) complex 20-S-proteasome using a specific atomic force microscopic setup. Analytical and structural data of these AFM-scans and abovementioned methods were likened (chapter 4.6). The deviations concerning the detected proportions were discussed regarding functional integrity of the protein and with respect to potential methodically determined artifacts. (chapter 3.1.4.3). Assaying (qualitative and quantitative) the surface roughness properties of coronary artery stents, we found significant alterations of stent material induced by balloondilatation. We suppose, that changes in roughness of inner surface of coronary artery stents might induce clinical problems like acute stent-thrombosis and in-stent-restenosis. Finally these stents were coated with human thromboytes to investigate cell-stent-surface interactions. Surface-roughness correllated triggering of thrombocyte adhesion was evaluated by morphological analysis of AFM-scans. Finishing, we have investigated and concluding discussed the specific activation of vital thrombocytes by pharmacological substances (e.g. ADP) and by mechanical stimulation (due to AFM-associated tip-surface-interaction). The results of this work demonstrate, AFM-technology using optimized microscopic setup and object-specific adjusted measurement- and preparation- methods, is an new, powerful, microscopic technique, that allow real-3-dimensional morphological mapping up to submolecular range of resolution in vital cells and protein complexes. Moreover, this technology opens new dimensions in functional analytic of cell migration processes or cellular contractions and in evaluation of visco-elastic quantification of cell membranes. The advantage owed to the most currently available microscopic methods is the option of serial and reproducible measurement of vital cells and subcellular structures. In this respect, this new method might represent a methodical enrichment of the microscopic-morphological and functional oriented analysis-technique in future.

Les artéfacts métalliques entraînent un épaississement artéfactuel de la paroi des tuteurs en tomodensitométrie (TDM) avec réduction apparente de leur lumière. Cette étude transversale prospective, devis mesures répétées et observateurs avec méthode en aveugle, chez 24 patients consécutifs/71 tuteurs coronariens a pour objectif de comparer l’épaisseur de paroi des tuteurs en TDM après reconstruction par un algorithme avec renforcement des bords et un algorithme standard. Une angiographie coronarienne par TDM 256 coupes a été réalisée, avec reconstruction par algorithmes avec renforcement des bords et standard. L’épaisseur de paroi des tuteurs était mesurée par méthodes orthogonale (diamètres) et circonférentielle (circonférences). La qualité d’image des tuteurs était évaluée par échelle ordinale, et les données analysées par modèles linéaire mixte et régression logistique des cotes proportionnelles. L’épaisseur de paroi des tuteurs était inférieure avec l’algorithme avec renforcement des bords comparé à l’algorithme standard, avec les méthodes orthogonale (0,97±0,02 vs 1,09±0,03 mm, respectivement; p<0,001) et circonférentielle (1,13±0,02 vs 1,21±0,02 mm, respectivement; p<0,001). Le premier causait moins de surestimation par rapport à l’épaisseur nominale comparé au second, avec méthodes orthogonale (0,89±0,19 vs 1,00±0,26 mm, respectivement; p<0,001) et circonférentielle (1,06±0,26 vs 1,13±0,31 mm, respectivement; p=0,005) et diminuait de 6 % la surestimation. Les scores de qualité étaient meilleurs avec l’algorithme avec renforcement des bords (OR 3,71; IC 95% 2,33–5,92; p<0,001). En conclusion, la reconstruction des images avec l’algorithme avec renforcement des bords génère des parois de tuteurs plus minces, moins de surestimation, et de meilleurs scores de qualité d’image que l’algorithme standard. / Metallic artifacts can result in an artificial thickening of the coronary stent wall which can significantly impair computed tomography (CT) imaging in patients with coronary stents. The purpose of this study is to assess the in vivo visualization of coronary stent wall and lumen with an edge-enhancing CT reconstruction kernel, as compared to a standard kernel. This is a prospective cross-sectional study of 24 consecutive patients with 71 coronary stents, using a repeated measure design and blinded observers, approved by the Local Institutional Review Board. 256-slice CT angiography was used, as well as standard and edge-enhancing reconstruction kernels. Stent wall thickness was measured with orthogonal and circumference methods, averaging wall thickness from stent diameter and circumference measurements, respectively. Stent image quality was assessed on an ordinal scale. Statistical analysis used linear and proportional odds models. Stent wall thickness was inferior using the edge-enhancing kernel compared to the standard kernel, either with the orthogonal (0.97±0.02 versus 1.09±0.03 mm, respectively; p<0.001) or circumference method (1.13±0.02 versus 1.21±0.02 mm, respectively; p<0.001). The edge-enhancing kernel generated less overestimation from nominal thickness compared to the standard kernel, both with orthogonal (0.89±0.19 versus 1.00±0.26 mm, respectively; p<0.001) and circumference (1.06±0.26 versus 1.13±0.31 mm, respectively; p=0.005) methods. The average decrease in stent wall thickness overestimation with an edge-enhancing kernel was 6%. Image quality scores were higher with the edge-enhancing kernel (odds ratio 3.71, 95% CI 2.33–5.92; p<0.001). In conclusion, the edge-enhancing CT reconstruction kernel generated thinner stent walls, less overestimation from nominal thickness, and better image quality scores than the standard kernel.

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).

Made available in DSpace on 2016-01-26T12:51:38Z (GMT). No. of bitstreams: 1 celsomurilonmdefaria_dissert.pdf: 1426679 bytes, checksum: 62fc4b90d691c716aef67c9e6590368e (MD5) Previous issue date: 2011-11-22 / Introduction: the utilization of endoprosthesis has its main indication in the neoplasic obstructions do not surgically treatable. The foreign industry dependence is one of the barriers we found for the broad utilization of such devices. The relevance of this research is the development of a national prosthesis from easy access and low cost. Objective: to assess the biocompatibility of nitinol endoprosthesis with polyurethane in the rabbits trachea. Material and Method: Seventeen rabbits were studied from the New Zealand breed (Oryctolagus Sylvilagus), eight male and five female, with an average weight of 3255g (from 2570 to 4270g). The endoprosthesis were applied orally through laringoscopy, under general anesthesia and released in the middle third of the trachea. Radiological study was made to assure the placement of the endoprosthesis that allowed to compare the index of migration of the endoprosthesis in millimeters. The proposed time segment was 30 days. The microscopic variables study was proceeded: dilatation, incorporation and granolomatous tissue and histological cuts from the tracheal and lungs segments for microscopic study. The histological study measured the inflammatory process, the parietal alterations and the kind of epithelium observed in the tracheal bed. Results: Thirteen animals were included in the final study. The average segment time was 26 days (15 to 35 days in observation). Six animals underwent a radiological study during euthanasia and it was demonstrated displacement with migration of the prosthesis for the distal trachea in five animals. There was absence in one. It was shown the prosthesis had a complete expansion in seven animals and partial expansion in six. The incorporation of prosthesis in the tracheal lumen was observed in two animals and adhered in eleven. Granulomatous tissue was present in ten animals and absent in three. The histological study of the mucosa and submucosa showed inflammatory process predominantly of Polymorphonuclear cells as in the contact region with the prosthesis as in the proximal. The depth of the inflammatory process in the tracheal wall was larger in the tracheal area in contact with the prosthesis. The alterations of the respiratory epithelium: the metaplasia parameter was the most frequent in the area without contact with the prosthesis. Corrosion and ulceration were predominant in the area in contact with the prosthesis. The metaplasia parameter was the most frequent in the area in contact with the prosthesis. Conclusion: the nitinol endoprosthesis auto-expandable covered with polyurethane, produced by Braile Biomédica and implanted in the trachea of rabbits was easy to apply and liberation in the tracheal lumen. The endoprosthesis recovered with polyurethane showed in radiographic assessment distal migration, good radial expandability and formation of granuloma tissue. It was also observed an inflammatory process predominantly acute and restricted to the superficial portions of the trachea. The most frequent epithelium alterations in contact with the prosthesis were ulceration and regenerative hyperplasia. / Introdução: a utilização de endoprótese tem a principal indicação nas obstruções neoplásicas e nas obstruções não tratáveis cirurgicamente. A dependência da indústria estrangeira é uma das barreiras para utilização ampla destes dispositivos. A relevância deste trabalho é o desenvolvimento de uma prótese nacional de fácil acesso e baixo custo. Objetivo: avaliar endoprótese de nitinol revestida com poliuretano, na traqueia de coelhos. Material e Método: foram estudados 17 coelhos, da raça Nova Zelândia (Oryctolagus Cuniculus). Oito machos e nove fêmeas, com peso médio de 3522g (de 2570 a 4270g). As endopróteses foram aplicadas via oral, por meio de laringoscopia, sob anestesia geral, e liberadas no terço médio das traqueias. Realizou-se estudo radiológico para assegurar a posição da endoprótese que permitiu comparar o índice de migração da endoprótese em milímetros. O tempo proposto de seguimento foi de 30 dias. Procedeu-se ao estudo das variáveis macroscópicas: dilatação, incorporação e tecido de granulação e cortes histológicos dos segmentos traqueais e pulmonares para estudo microscópico. O estudo histológico mensurou o processo inflamatório, as alterações parietais e o tipo de epitélio observado no leito traqueal. Resultados: 13 animais foram incluídos no estudo definitivo. O tempo médio de seguimento foi 26 (15 a 35) dias em observação. Em seis animais submetidos a estudo radiológico por ocasião da eutanásia, demonstrou-se deslocamento com migração da prótese para traqueia distal, em cinco; ausência de migração em um. Demonstrou-se que a prótese tinha expansão completa em sete animais e parcial em seis. A incorporação da prótese na luz traqueal foi observada em dois animais, e aderido em 11. Tecido de granulação esteve presente em dez animais e ausente em três. O estudo histológico da mucosa e submucosa demonstrou processo inflamatório com predomínio de polimorfonucleares tanto na região em contato com a prótese quanto na proximal. A profundidade do processo inflamatório na parede traqueal foi maior na área traqueal em contato com a prótese. Das alterações do eptélio respiratório, o parâmetro metaplasia foi o mais frequente na área sem contato com a prótese. Corrosão e ulceração predominaram na área em contato com a prótese. Conclusões: A escolha do coelho no desenho do presente estudo prejudicou o resultado. Trata-se de estudo pioneiro tanto na utilização de coelho para estudo de endoprótese, quanto no desenvolvimento de endoprótese metálica autoexpansível nacional. As dificuldades foram naturais deste pioneirismo, mas prejudicaram o resultado final. A endoprótese autoexpansível de nitinol recoberta de poliuretano, produzida pela Braile Biomédica Ltda, (Brasil) e implantada na traqueia de coelhos, demonstrou-se de fácil aplicação e liberação na luz traqueal. Apresentou elevada taxa de migração, boa expansibilidade radial. Verificou-se alta frequência na formação de tecido de granulação e baixa permeabilidade. Observou-se ainda processo inflamatório predominantemente agudo e restrito ás porções superficiais da traquéia. As alterações epiteliais mais freqüentes em contato com a prótese foram ulceração e hiperplasia regenerativa.

La pose de stent est l'option de traitement la plus courante de la maladie coronarienne, l'une des principales causes de mortalit e dans le monde. Lors d'une proc edure de pose de stent, le m edecin ins ere des outils chirurgicaux dans le r eseau vasculaire du patient. La progression de ces outils a l'int erieur du corps est suivie en temps r eel sous fluoroscopie par rayons X. Trois outils, en particulier, jouent un role crucial dans la proc edure : le guide, le ballon d'angioplastie et le stent. Le guide apparait dans les images sous la forme d'une structure curviligne. Le ballon, mont e sur le guide, est equip e de deux marqueurs radio-opaques a ses extr emit es. Le stent est un maillage m etallique qui se projette en une forme complexe dans les images fluoroscopique. Le stent, dont le bon d eploiement est essentiel au succ es du geste m edical, est souvent tr es diffi cilement visible dans les images. Les travaux pr esent es dans cette th ese poursuivent un double objectif. Il s'agit d'une part, de concevoir, d' etudier et de valider des techniques de traitement d'image visant a am eliorer la visualisation des stents. D'autre part, nous etudions le traitement des structures curvilignes (comme les guides) pour lesquelles nous proposons un nouvel outil. Nous pr esentons des algorithmes de traitement d'image d edi es a la visualisation 2D et 3D des stents. Nous sommes amen es, dans ce but, a d etecter, suivre et recaler, de mani ere compl etement automatique, les outils n ecessaires a la pose de stent que sont le guide et le ballon. Le stent etant a peine visible dans les images, nous ne cherchons pas a le localiser directement a l'aide de techniques de traitement d'images. La position et le mouvement du stent sont d etermin ees par nos algorithmes a partir de celles de deux amers: le guide et le ballon qui ont des formes caract eristiques. Nous eff ectuons donc, dans ce but, la d etection, le suivi et le recalage de ces amers, et ce de mani ere compl etement automatique. Le coe ur de notre m ethode de visualisation des stents en 2D r eside dans l'utilisation des amers pour effectuer un d ebruitage compens e en mouvement. Nous avons evalu e la performance des ces outils pour la visualisation des stents en 2D, sur une large base de pr es de 200 cas cliniques. Il en ressort que notre m ethode surpasse les m ethodes utilis ees jusqu'ici sur le plan de la qualit e image. La validation exhaustive que nous avons men e, a confi rm e que nous avions atteint un niveau compatible avec son introduction commerciale. Le logiciel qui en r esulte est d esormais install e sur un grand nombre de sites cliniques, o u il est r eguli erement utilis e. La m ethode de visualisation 3D des stents que nous proposons utilise les amers pour e ffectuer une reconstruction tomographique compens ee en mouvement. Nous exposons des r esultats pr eliminaires sur une base de 22 cas cliniques. Il semble que notre m ethode surpasse les m ethodes pr ec edemment employ ees aussi bien du point de vue de la qualit e image que de l'automatisation. Les m ethodes de visualisation des stents que nous proposons s'appuient sur la segmentation de la portion du guide qui traverse le stent. Nous proposons un nouvel outil pour le traitement de telles structures curvilignes que nous appelons : l'Image de Chemins Polygonaux (acronyme PPI en anglais). Cet outil repose sur la notion de chemin localement optimal. L'un des principaux avantages du PPI est d'uni er dans un meme cadre diff erents concepts pr e-existants. De plus, il permet de controler la r egularit e et la longueur des structures a traiter avec une param etrisation simple et intuitive. A n de tirer pleinement parti des performances du PPI nous proposons un sch ema algorithmique effi cace pour le calculer. Nous illustrons ses utilisations pour la segmentation automatique de guide ou il surpasse les techniques existantes.

Venous disease will affect 1-3% of the western world at some point in their lives, yet there are few effective treatments for the venous system [1]. One such disease is chronic venous insufficiency (CVI), a painful and debilitating illness that affects the superficial and deep vein valves of the legs. When the valves become incompetent they allow reflux and subsequent pooling of blood. Current clinical therapies are only moderately; and therefore, the need for a better solution remains. Prosthetic venous valves were constructed from a novel hydrogel biomaterial patented by Georgia Tech. The valves had flexible cusps similar to normal, anatomic venous valves. The purpose of this work was to evaluate the thrombotic potential of the GT venous valve in an in vitro study and to design a percutaneous delivery system. In vitro thrombosis model provides an appropriate intermediate step between valve development and in vivo analysis, which is necessary to determine the biocompatibility of the prosthetic device. The flow system was modified from a one-pass, flow-through thrombosis assay using whole blood [2] to mimic pulsatile physiologic conditions. Cessation of flow indicated thrombotic obstruction. Histological analysis was performed using H and E staining and Carstairs stain (specific for platelets). A group of valves were lined with Dacron to confirm the thrombotic potential of the system. All Dacron valves were occluded by thrombus connecting the polymer fibers with adherent platelets. Whole blood perfused through the GT prosthetic valves exhibited no thrombosis or platelet adherence. All GT valves were patent and competent after blood perfusion. H and E staining revealed no thrombus deposition on the GT vein valves. A percutaneous delivery system was designed after evaluating the GT valves for their compressibility and plastic deformation over time. Appropriate stents, catheters and sheaths were selected. As designed, this system will be utilized in an ovine trial of the valve. Due to the low in vitro thrombotic potential and strong history of PVA as a medical implant material, positive trial results are expected. With successful animal and human trials this valve can provide a potential intervention for the 7 million people suffering from CVI.

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).

Submitted by Natalia de Souza Gonçalves (natalia.goncalves@ufpe.br) on 2016-10-10T13:09:11Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) GALENO EGYDIO - COLACAO DE GRAU.pdf: 1509311 bytes, checksum: f4dc67e7a0e6a1a9159df433631ba569 (MD5) / Made available in DSpace on 2016-10-10T13:09:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) GALENO EGYDIO - COLACAO DE GRAU.pdf: 1509311 bytes, checksum: f4dc67e7a0e6a1a9159df433631ba569 (MD5) Previous issue date: 2014-02-19 / O uso de anel na derivação gástrica em Y de Roux (DGYR) está associado à intolerância alimentar pós-operatória, cujo tratamento clássico tem sido a remoção cirúrgica. Um novo método utilizando prótese plástica autoexpansível (PPAE) induz erosão intragástrica do anel, o qual é removido por via endoscópica de forma minimamente invasiva. Objetiva-se analisar a eficácia e a segurança dessa técnica de remoção de anel após DGYR. Estudo prospectivo longitudinal de série de 41 pacientes com intolerância alimentar associada à presença de anel, que foram, tratados por via endoscópica, entre 2007 e 2013. O grupo apresentava média de idade igual a 44,1 anos, IMC médio de 27,0 Kg/m², e vômitos foram os sintomas mais frequentes (n=37), com ocorrência diária em 46,3%. O sucesso terapêutico foi definido como a melhora dos sintomas após a remoção do anel. O implante de PPAE foi realizado sob anestesia geral e guiado por radioscopia, sendo utilizado endoscópio padrão. Os pacientes receberam alta após 24 horas com dieta líquida e inibidor de bomba de prótons (IBP), que foi prescrito durante o tempo médio de permanência da PPAE, que foi de 15,3 dias. A prótese promoveu erosão completa de anel em 24 (58,5%) pacientes e no grupo restante, a remoção em segundo estágio após 7 dias com pinça de corpo estranho. Houve três casos de migração da prótese com eliminação espontânea por via retal. O efeito adverso mais comum foi vômito (n=7). Não houve complicações graves, nem necessidade de remoção precoce da prótese. Após seguimento médio de 6 meses, não houve mudança significativa no IMC e 78% dos pacientes foram capazes de ingerir carne vermelha. A remoção do anel com uso de prótese endoscópica demonstrou ser um procedimento seguro e eficaz, com100% dos anéis sendo removidos com sucesso e 29,3% de ocorrência de eventos adversos leves (vômitos). Esta técnica é uma alternativa adequada na remoção do anel, evitando a intervenção cirúrgica e reduzindo a possibilidade de reganho de peso. / Ring dysfunction after roux-en-y gastric bypass (RYGB) causing delayed gastric emptying on Fobi pouch is classically treated by surgical ring removal. In a novel way of using selfexpandable stents, intraluminal erosion of the ring is achieved, allowing its removal by endoscopy, with no need of surgery. No study has shown clinical applicability of this principle in RYGB banded with silastic ring. In this case series we analyze endoscopic removal of noneroded dysfunctional rings after RYGB using self-expandable plastic stents (SEPS). This is a prospective case series of 41 patients with delayed gastric emptying secondary to extrinsic compression of the ring after RYGB between 2007 and 2013. Successful ring removal, symptoms improvement, weight control and adverse events were evaluated. Mean age of subjects was 44.1 years, median BMI at treatment was 27.0 Kg/m2. Most common symptom was vomiting (n=37), with daily occurrence in 46.3%. Success was defined as symptoms improvement after stent and ring removal. SEPS placement was done under general anesthesia and fluoroscopic guidance. A standard gastroscope (Pentax Medical, Montvale, NJ), and a PolyflexTM stent (25x21x150mm) (Boston Scientific, Natick, MA) were used in all cases. All patients were discharged after a 2-hour observation period, with liquid diet and proton pump inhibitor. SEPS induced complete erosion in 24 patients, allowing for simultaneous stent and ring removal. The median time of stenting was 15 days. There was one case of stent migration, which was naturally expelled. Most common adverse event was vomiting (n=7). There was no early stent removal, and no serious complications. After a mean follow-up of 6 months, there was no significant change in mean BMI, and 78% of patients are able to ingest solid foods. Endoscopic stents led to ring intraluminal erosion in 100% of subjects, allowing for successful removal of dysfunctional rings. The procedure is technically feasible and safe, with a 29.3% occurrence of mild adverse events (vomiting), and no serious complications. It proved to be a reasonable alternative for ring removal in our casuistic, avoiding surgery, and decreasing the possibility of weight regain.

La sélection de variables est une tâche primordiale en fouille de données et apprentissage automatique. Il s’agit d’une problématique très bien connue par les deux communautés dans les contextes, supervisé et non-supervisé. Le contexte semi-supervisé est relativement récent et les travaux sont embryonnaires. Récemment, l’apprentissage automatique a bien été développé à partir des données partiellement labélisées. La sélection de variables est donc devenue plus importante dans le contexte semi-supervisé et plus adaptée aux applications réelles, où l’étiquetage des données est devenu plus couteux et difficile à obtenir. Dans cette thèse, nous présentons une étude centrée sur l’état de l’art du domaine de la sélection de variable en s’appuyant sur les méthodes qui opèrent en mode semi-supervisé par rapport à celles des deux contextes, supervisé et non-supervisé. Il s’agit de montrer le bon compromis entre la structure géométrique de la partie non labélisée des données et l’information supervisée de leur partie labélisée. Nous nous sommes particulièrement intéressés au «small labeled-sample problem» où l’écart est très important entre les deux parties qui constituent les données. / Feature selection is an important task in data mining and machine learning processes. This task is well known in both supervised and unsupervised contexts. The semi-supervised feature selection is still under development and far from being mature. In general, machine learning has been well developed in order to deal with partially-labeled data. Thus, feature selection has obtained special importance in the semi-supervised context. It became more adapted with the real world applications where labeling process is costly to obtain. In this thesis, we present a literature review on semi-supervised feature selection, with regard to supervised and unsupervised contexts. The goal is to show the importance of compromising between the structure from unlabeled part of data, and the background information from their labeled part. In particular, we are interested in the so-called «small labeled-sample problem» where the difference between both data parts is very important.

Les nouvelles technologies médicales contribuent aux dépenses en santé qui ne cessent de croître, alors que les budgets se trouvent limités. L’évaluation économique des technologies devraient permettre d’identifier quelles sont celles qui sont les plus rentables. Malgré cela, plusieurs technologies dont le rapport coût-efficacité reste plutôt limite ou défavorable sont utilisées en médecine moderne et remboursées par notre système public de santé. Ce mémoire se concentre sur deux technologies en santé cardiovasculaire dont le rapport coût-efficacité est plutôt limite mais qui sont fréquemment utilisées au Canada; les tuteurs médicamentés ou pharmaco-actifs et les défibrillateurs cardiaques implantables (DCI). Nous avons fait une évaluation contingente de ces technologies dans le but d’examiner si ce type d’évaluation économique complémentaire pouvait procurer un point de vue nouveau sur la valeur économique et sociétaire des ces technologies. Les résultats de ces deux évaluations indiquent que les patients accordent une grande importance aux bénéfices que procurent ces deux technologies. Nos résultats soutiennent les politiques de santé actuelles de rembourser de façon libérale ces deux technologies. / Technological innovations have greatly contributed to the rising costs in healthcare, while budgets have remained limited. Economic evaluations of technologies should identify which technologies are cost-effective. However, several technologies used in modern medicine are either borderline cost-effective or even not cost-effective according to many studies. This thesis focuses on two technologies in cardiovascular medicine which are considered borderline cost-effective; drug-eluting stents and implantable cardioverter defibrillators. We conducted a contingent valuation of these technologies in hopes of determining if this alternative type of economic evaluation could give a novel point of view on the economic and societal value of these technologies. Results indicated that patients greatly valued benefits provided by these two technologies. Our result support our public healthcare system policies’ of liberal reimbursement of these two technologies.