Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-23T15:05:11Z No. of bitstreams: 1 TES_EDUARDO_HERZ_BERDICHEVSKI_PARCIAL.pdf: 1111972 bytes, checksum: 207ba6b7db85b282db30b671c8ca89b8 (MD5) / Made available in DSpace on 2017-06-23T15:05:11Z (GMT). No. of bitstreams: 1 TES_EDUARDO_HERZ_BERDICHEVSKI_PARCIAL.pdf: 1111972 bytes, checksum: 207ba6b7db85b282db30b671c8ca89b8 (MD5) Previous issue date: 2017-01-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / It has been shown that the use of contrast media in PET/CT (positron emission tomography/ computed tomography) studies is beneficial when compared to an unenhanced CT scan. This is due to the fact that contrast media generates better contrast regarding adjacent structures, allows better characterization of abnormalities, and also allows visualizing alterations that do not present abnormal metabolic behavior. However, contrast agents generate more absorption of CT photons in relation to those of PET potentially giving rise to errors in attenuation correction of PET images. Errors converting the attenuation map from the CT to the PET scan may lead to inaccurate quantification of PET images. The occurrence of SUV (Standardized uptake value) modifications in lesions when PET images are corrected with either contrast-enhanced or unenhanced CT scans has already been studied. Our goal, however, was to study the occurrence of such alterations in relation with lesion size, and distance from the lesion to areas of high contrast concentration, such as high caliber vases and focal areas of the gastrointestinal tract (GIT). Methods: We obtained the SUVmax of 149 lesions, from 26 patients who underwent a PET/CT scan in which images were corrected using both an unenhanced computed tomography (PETCTUE) and a contrast-enhanced computed tomography (PETCTCE). In addition, we measured lesion sizes (smallest and largest diameter, and area) and their distance to large vessels and the GIT. Size measures were not taken when the lesion could not be visualized in the CT image. For lesions in which the distance to high contrast concentration areas was too large or too small, and could not be accurately estimated, the median distance of similar lesions was used to replace the measures. Following the repeated measures principle, we obtained Lin's concordance correlation coefficient and its confidence interval. A Bland-Altman analysis was performed using the absolute difference values and ratio, between PETCTCE and PETCTUE with concordance limits. Results: A total of 149 lesions could be visualized in PET. Eleven of them could not be identified in the CT, and so their measurements were not taken. For 16 lesions, the distance to high contrast concentration areas could not be obtained. The concordance level between the methods, by Lin's concordance correlation coefficient, was 0.99 (CCC: 0.99), and the confidence interval was 95% of 0.98 ? 0.99 (IC95%: 0.98 ? 0.99). The mean absolute difference between the methods was approximately zero and the relative difference was +3.37% (concordance limits of 95% between -2.72 and +2.72, and between -15.73 and +22.48%, respectively). Eighty-two lesions had their larger diameter below 17mm and the other 56 had a larger diameter above or equal to 17mm, with mean percent variation of SUVmax from PETCTCE to PECCTUE of 3.85% and 2.83%, respectively (p=0.54). Sixty-six lesions had a smaller diameter below 17mm and the remaining 72 had a smaller diameter equal to or above 17mm. The mean percent SUVmax variation from PETCTCE to PECCTUE was 2.71%?1,74 and 3.80% ?1,60, respectively (p=0.41). Eighty-two lesions had an area larger than 2.27 cm2 and the other 57 had an area equal to or larger than 2.27 cm2. The mean percent variation of the SUVmax obtained for PETCTCE and PETCTUE was 2.81%?1.64 e 3,83%?1.70, respectively (p=0.48). Sixty-seven lesions were more than 1.82 cm distant from large vessels/ GIT, and 82 were at a less than 1cm distance. The mean SUVmax variation between the methods (PETCTCE versus PETCTUE) was 0.57?1.65% e 4.98?1.61% respectively (p < 0.005). Conclusions: For the totality of studied lesions (149), as well as for the analysis regarding the factors size (non significant p) and distance (significant p), the medium SUVmax variation we identified it not clinically relevant. Thus, both contrast-enhanced and unenhanced PET/CT can be used for attenuation correction. / Nos estudos de PET/CT (tomografia por emiss?o de p?sitrons/ tomografia computadorizada), o uso de material contrastado endovenoso na CT mostra benef?cios diagn?sticos em rela??o a CT n?o contrastada. Isto ocorre pois o material contrastado al?m de gerar maior contraste entre as les?es em rela??o ?s estruturas adjacentes, e melhor caracterizar as anormalidades, tamb?m permite a visualiza??o de altera??es que n?o demonstram comportamento metab?lico anormal. Entretanto, os meios de contraste geram maior absor??o dos f?tons da CT em rela??o aos do PET, e isto tende a gerar erros na corre??o de atenua??o das imagens do PET. Esses erros na convers?o do mapa de atenua??o da CT para o do PET podem levar a inacur?cias na quantifica??o das imagens do PET. A ocorr?ncia de altera??es do SUV das les?es entre as imagens de PET corrigidas para atenua??o com o CT sem contraste e com o CT contrastado j? foi amplamente estudada. Nosso objetivo foi estudar essa ocorr?ncia em fun??o do tamanho das les?es e das dist?ncias entre elas e zonas de maior concentra??o de contraste, como ? o caso de vasos calibrosos e ?reas focais em trato gastrintestinal (TGI). M?todos: Mensuramos o SUVmax de 149 les?es em 26 pacientes cujos exames de PET/CT foram corrigidos tanto utilizando tomografia n?o-contrastada (PETCTSC) quanto tomografia contrastada (PETCTCC). Al?m disso, medimos as dimens?es das les?es (maior e menor di?metro e ?rea) e suas dist?ncias para vasos calibrosos e TGI. Medidas de tamanho n?o foram feitas quando n?o foram visualizadas na CT. Em les?es cujas dist?ncias de ?reas de maior contraste n?o puderam ser feitas com seguran?a por serem muito pr?ximas ou muito grandes, suas medidas foram repostas pela mediana de les?es similares quanto a este aspecto. Seguindo o princ?pio de medidas repetidas, obteve-se o n?vel de concord?ncia dos m?todos atrav?s do coeficiente de correla??o de concord?ncia de Lin e seu respectivo intervalo de confian?a. Realizou-se uma an?lise de Bland-Altman cruzando os valores de diferen?a absoluta e de raz?o entre o PETCTCC versus o PETCTSC com os limites de concord?ncia. Resultados: Das 149 les?es visualiz?veis no PET, 11 n?o demonstraram correspond?ncia na CT, n?o sendo mensuradas suas dimens?es. Dezesseis les?es n?o tiveram calculadas as suas dist?ncias para alguma ?rea de maior concentra??o de contraste e seus valores foram repostos. O n?vel de concord?ncia dos m?todos, pelo coeficiente de correla??o de concord?ncia de Lin, foi de 0.99 (CCC: 0.99) com intervalo de confian?a de 95% de 0.98 ? 0.99 (IC95%: 0.98 ? 0.99). A diferen?a m?dia absoluta entre os m?todos foi de aproximadamente zero e relativa de +3.37% (limites de concord?ncia de 95% entre -2.72 e +2.72 e entre -15.73 e +22.48% respectivamente). Oitenta e duas les?es apresentaram maior di?metro abaixo de 17mm e as outras 56, igual ou acima de 17mm, com diferen?a m?dia percentual dos SUVmax medida nos PETCTCC e PETCTSC igual a 3,85%?1,65 e 2,83%?1,80 respectivamente (p = 0,54). Sessenta e seis les?es apresentaram menor di?metro abaixo do que 17mm e as demais 72, di?metro igual ou acima de 17mm. A diferen?a m?dia percentual dos SUVmax medida nos PETCTCC e PETCTSC foi igual a 2,71%?1,74 e 3,80% ?1,60 respectivamente (p = 0,41). Oitenta e uma les?es apresentaram ?rea menor que 2,27 cm2 e as outras 57, ?rea igual ou maior que 2,27 cm2. A diferen?a m?dia percentual dos SUVmax medida nos PETCTCC e PETCTSC foi igual a 2,81%?1,64 e 3,83%?1,70 respectivamente (p = 0,48). Sessenta e sete les?es tinham dist?ncia de vasos calibrosos/ TGI acima de 1cm, e 82, igual ou menor que 1cm. A diferen?a m?dia percentual entre os m?todos (PETCTCC versus PETCTSC) foi igual a 0,57?1,65% e 4,98?1,61% respectivamente (p < 0,005). Conclus?es: Mesmo para o grupo total de les?es (149) bem como para os grupos de les?es separados em fun??o dos fatores ?tamanho? (p n?o significativo) e ?dist?ncia? (p significativo), a varia??o m?dia do SUVmax visualizada n?o tem relev?ncia cl?nica, tornando intercambi?vel a corre??o do PET pelo CT sem e com contraste.

Much of our knowledge of cellular biology arises from direct observation of active cellular functions. Tools and techniques have steadily developed over the past several hundreds of years to aid in our understanding and control of the nanoworld and are referred to as nanotechnologies. In the context of nanotechnology, DNA is not used as a carrier for genetic information (as it is in cell), but as a construction material. DNA offers unprecedented control over the construction of simplified biomimetic models for the study of biological processes. This thesis first introduces and defines the field of DNA nanotechnology, with particular emphasis on the interaction of snthetic DNA nanostructures with biological membranes. Inspired by the protein clathrin, three-fold symmetric DNA tile made of eight, short DNA strands and capable of polymerising is described and studied, with the aim to interact with and controllably bend a membrane bilayer. This structure presented challenges during construction so an enhanced three-armed DNA structure built with DNA origami was designed. The succesful assembly of a rigid and functionalisable nanostructure is described. This origami structure was polymerised into large constructs in solution and on a supported lipid membrane. The shape of the structure was modulated to vary its curvature and apply a bending force to a lipid vesicle when anchored to it. Following the conclusion of this study, we present the construction of a small, unique DNA structure for enhanced electron microscopy imaging in cell lysate. This project is part of a developing technique to couple the interaction specificity of dyes in super-resolution microscopy and the high-resolution output of electron microscopy. Finally, the optimisation procedures and recommendations for TEM imaging of samples of DNA origami and lipid structures are discussed.

La Tomographie par Emission de Positons (TEP) au Fluoro-déoxyglucose marqué au Fluor 18 (¹⁸F-FDG), analogue du glucose, permet d'obtenir une image de la consommation de glucose dans l'organisme. La plupart des foyers tumoraux présentant une consommation excessive de glucose, son utilisation en oncologie permet d'améliorer la prise en charge des patients en diminuant le temps nécessaire pour évaluer l'efficacité des traitements tels que la chimiothérapie et la radiothérapie. Mon projet de recherche visait à proposer et améliorer des méthodes de quantification en TEP au ¹⁸F-FDG afin de caractériser au mieux l'évolution métabolique des volumes tumoraux.De nombreux facteurs biaisent la quantification en TEP. Parmi eux, l'Effet de Volume Partiel (EVP) reste difficile à corriger, notamment à cause de la faible résolution spatiale des images TEP. Afin de déterminer l'impact de la correction de l'EVP sur l'évaluation des réponses des tumeurs, une étude sur données simulées par Monte Carlo a tout d'abord été effectuée. Cette étude a été complétée par l'analyse de données TEP/TDM (Tomodensitométrie) acquises chez 40 patients atteints de cancers colorectaux métastatiques (CCM), traités par chimiothérapie à l'Institut Jules Bordet (Bruxelles). L'analyse de 101 tumeurs a montré que les critères tels que le SUV, n'incluant pas de correction de l'EVP, et qui reflètent alors le volume tumoral et son activité, prédisaient mieux l'évolution tumorale que les critères corrigés de l'EVP. Compte tenus des résultats prometteurs récents de méthodes de caractérisation de l'hétérogénéité de la fixation du FDG dans les tumeurs, un second volet de notre travail a consisté à étudier l'intérêt de la prise en compte de la texture dans le cadre du suivi thérapeutique. L'application de l'analyse de texture aux cas de CCM étudiés précédemment n'a pas permis de démontrer une valeur ajoutée des indices de texture par rapport aux index quantitatifs couramment employés en clinique. Nous avons montré que cette conclusion s'expliquait en partie par la non-robustesse des indices de texture vis-à-vis des paramètres impliqués dans leur mesure. Nous avons enfin cherché à évaluer une méthode d'Analyse Factorielle de Séquences d'Images Médicales (AFSIM), appliquée au contexte du suivi thérapeutique, pour caractériser l'évolution tumorale tout au long du traitement. Cette étude a porté sur 9 séries de 4 à 6 examens TEP/TDM de patients traités par radiothérapie au Centre Hospitalier Universitaire Henri Becquerel de Rouen. Outre l'information visuelle globale apportée par cette méthode, l'analyse quantitative des résultats obtenus a permis de caractériser l'hétérogénéité de la réponse vue par l'AFSIM. L'échec des index classiques, provenant entre autres de leur incapacité à distinguer les processus inflammatoires de l'activité métabolique tumorale, a permis de monter la valeur ajoutée de l'AFSIM par rapport aux index tels que le SUV maximal ou moyen.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22305号 / 医博第4546号 / 新制||医||1040(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 鈴木 実, 教授 溝脇 尚志 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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[ES] Los estudios realizados en el pasado han demostrado que, a pesar de tener cero emisiones del tubo de escape, un vehículo completamente eléctrico tiene emisiones durante el ciclo de vida. El desarrollo tecnológico a lo largo de los años por parte de la humanidad ha llevado constantemente a un aumento de la dependencia energética. Desafortunadamente, esta energía proviene principalmente de fuentes fósiles. Uno de los principales consumidores de energía de origen fósil es la industria del transporte, que utiliza petróleo y diesel como combustibles. Estos combustibles se queman en motores de combustión interna para producir energía debido a su alto poder calorífico. Dado que estos son combustibles a base de carbono, genera dióxido de carbono durante el proceso, que es un gas de efecto invernadero. Por lo tanto, ha habido un seguimiento y una regulación muy estrictos de los tubos de escape de los automóviles a lo largo de los años. Recientemente, diferentes regiones del mundo han planeado prohibir la venta de vehículos convencionales basados en motores de combustión interna. Por lo tanto, vender solo vehículos con cero emisiones de escape, como vehículos eléctricos de batería y vehículos eléctricos de pila de combustible. Esto se debe principalmente a la intensidad de las emisiones de la combinación de electricidad, para alimentar las baterías y el proceso de fabricación de baterías para vehículos eléctricos de batería. Mientras que los vehículos eléctricos de pila de combustible dependen de la intensidad de emisión de la producción de hidrógeno. Dado que la producción actual de hidrógeno es muy limitada y tiene un alto contenido de carbono, los vehículos eléctricos de batería son los preferidos para reemplazar a los vehículos con motor de combustión interna. Otra razón detrás del impulso de este cambio es la alta eficiencia de los sistemas de propulsión eléctricos. A pesar de eso, es muy difícil para los vehículos eléctricos de batería igualar el rango de conducción de los vehículos con motor de combustión interna debido a la gran diferencia en la densidad de energía de las baterías y los combustibles líquidos. En condiciones reales de conducción, este rango de conducción es aún más reducido, a pesar de tener grandes paquetes de baterías a bordo. Esta es una limitación importante para el uso de vehículos eléctricos de batería, hasta que se desarrolle una infraestructura de carga extensa. Por ello, en esta tesis se evalúa el potencial de reducción de emisiones de los vehículos eléctricos con un enfoque de ciclo de vida para turismos y autobuses. Esto se hace comparando sus emisiones con las de los vehículos diésel convencionales y eléctricos híbridos para ciclos de conducción reales utilizando simulaciones numéricas 0D. Esto se complementa con estudios del costo del ciclo de vida de los diferentes vehículos para ver qué opción de tren motriz puede ser más eficiente. Además, los combustibles sintéticos bajos en carbono también se están evaluando como una solución alternativa para reemplazar el combustible diesel y ver el cambio que puede traer al ciclo de vida de los vehículos con motor de combustión interna. Estas evaluaciones se realizan para diferentes ubicaciones a nivel mundial para observar los factores locales que afectan los resultados. Por lo tanto, este trabajo tiene como objetivo evaluar los resultados del ciclo de vida para los responsables políticos y los fabricantes de automóviles a nivel mundial, tanto de las emisiones como del costo, asociados con cada opción de tren motriz. Como resultado de esta investigación, se observan varios desafíos relacionados con los vehículos eléctricos de batería que deben abordarse antes de su adopción masiva. Por lo tanto, se propone el uso de vehículos híbridos como una solución a corto plazo para abordar la urgencia de reducción de emisiones globales. Lo cual, de hecho, también puede considerarse una solución a largo plazo si funciona con combustibles bajos en carbono. / [CA] Els estudis realitzats en el passat han demostrat que, malgrat tenir zero emissions del tub d'escapament, un vehicle completament elèctric té emissions durant el cicle de vida. El desenvolupament tecnològic al llarg dels anys per part de la humanitat ha portat constantment a un augment de la dependència energètica. Desafortunadament, aquesta energia prové principalment de fonts fòssils. Un dels principals consumidors denergia dorigen fòssil és la indústria del transport, que utilitza petroli i dièsel com a combustibles. Aquests combustibles es cremen en motors de combustió interna per produir energia a causa del seu alt poder calorífic. Atès que són combustibles a base de carboni, genera diòxid de carboni durant el procés, que és un gas d'efecte hivernacle. Per tant, hi ha hagut un seguiment i una regulació molt estrictes dels tubs de fuga dels automòbils al llarg dels anys. Recentment, diverses regions del món han planejat prohibir la venda de vehicles convencionals basats en motors de combustió interna. Per tant, vendre només vehicles amb zero emissions d'escapament, com ara vehicles elèctrics de bateria i vehicles elèctrics de pila de combustible. Això es deu principalment a la intensitat de les emissions de la combinació delectricitat, per alimentar les bateries i el procés de fabricació de bateries per a vehicles elèctrics de bateria. Mentres que els vehicles elèctrics de pila de combustible depenen de la intensitat d'emissió de la producció d'hidrogen. Atès que la producció actual dhidrogen és molt limitada i té un alt contingut de carboni, els vehicles elèctrics de bateria són els preferits per reemplaçar els vehicles amb motor de combustió interna. Una altra raó darrere de l¿impuls d¿aquest canvi és l¿alta eficiència dels sistemes de propulsió elèctrics. Tot i això, és molt difícil per als vehicles elèctrics de bateria igualar el rang de conducció dels vehicles amb motor de combustió interna a causa de la gran diferència en la densitat denergia de les bateries i els combustibles líquids. En condicions reals de conducció, aquest rang de conducció encara és més reduït, tot i tenir grans paquets de bateries a bord. Aquesta és una limitació important per a lús de vehicles elèctrics de bateria, fins que es desenvolupi una infraestructura de càrrega extensa. Per això, en aquesta tesi s"avalua el potencial de reducció d"emissions dels vehicles elèctrics amb un enfocament de cicle de vida per a turismes i autobusos. Això es fa comparant les seves emissions amb les dels vehicles dièsel convencionals i elèctrics híbrids per a cicles de conducció reals utilitzant simulacions numèriques 0D. Això es complementa amb estudis del cost del cicle de vida dels diferents vehicles per veure quina opció de tren motriu pot ser més eficient. A més, els combustibles sintètics baixos en carboni també s'estan avaluant com a solució alternativa per reemplaçar el combustible dièsel i veure el canvi que pot portar al cicle de vida dels vehicles amb motor de combustió interna. Aquestes avaluacions es fan per a diferents ubicacions a nivell mundial per observar els factors locals que afecten els resultats. Per tant, aquest treball té per objectiu avaluar els resultats del cicle de vida per als responsables polítics i els fabricants d'automòbils a nivell mundial, tant de les emissions com del cost, associats amb cada opció de tren motriu. Com a resultat d'aquesta investigació, s'observen diversos desafiaments relacionats amb els vehicles elèctrics de bateria que cal abordar abans de la seva adopció massiva. Per tant, es proposa utilitzar vehicles híbrids com una solució a curt termini per abordar la urgència de reducció d'emissions globals. Això, de fet, també es pot considerar una solució a llarg termini si funciona amb combustibles baixos en carboni. / [EN] Several studies in the past have shown that despite having zero tailpipe emissions in a fully electric vehicle, it does have emissions when evaluated on a life cycle basis. Technology development over the years by humankind has constantly led to an increase in energy dependence. Unfortunately, this energy comes mainly from fossil-based sources that are limited. One major consumer of fossil-based energy sources is the transportation industry, which uses fossil-based petrol and diesel as fuels. These fuels are burned in internal combustion engines to produce energy due to their high calorific value. Since these are carbon-based fuels, it generates carbon dioxide during the combustion process, which is a greenhouse gas and leads to global warming. Therefore, there has been very strict monitoring and regulation of its emissions from the automotive tailpipes over the years. In recent years, different regions across the world have planned to completely stop the sale of conventional internal combustion engine-based vehicles. Thus, selling only zero tailpipe emission vehicles such as battery electric vehicles and fuel cell electric vehicles. This is primarily due to the emission intensity of the electricity mix used to power the batteries and from the battery manufacturing process for battery electric vehicles. At the same time, the fuel cell vehicle depends mainly on the emission intensity of hydrogen production. Since current hydrogen production is very limited and carbon-intensive, battery electric vehicles are highly favoured to replace internal combustion engine vehicles soon. Another reason behind the push for this shift is the high efficiency of electric powertrains. Despite that, it is very challenging for battery electric vehicles to match the driving range of internal combustion engine vehicles due to the large difference in the energy density of batteries and liquid fuels, currently. Further, in real driving conditions, this driving range is even more reduced for electric vehicles, even after having large battery packs on board. This is a major limitation for battery electric vehicles, especially for the ones meant for long haul routes, until an extensive charging infrastructure is developed. Therefore, in this thesis, the emission reduction potential of electric vehicles is evaluated following a life cycle approach for passenger cars and city buses. This is done by comparing their emissions with that of conventional diesel and hybrid electric vehicles for real driving cycles by means of 0D numerical simulations. This is complemented with life cycle cost studies for the different vehicles to see which powertrain option can be efficient in terms of emissions but also cost. Moreover, low-carbon synthetic fuels are also evaluated as an alternative drop-in solution to replace diesel fuel and see the change it can bring on a life cycle basis for hybrid and conventional internal combustion engine vehicles. These evaluations are done for different locations globally to observe the local factors that affect the results of each powertrain option for the two vehicle segments. Thus, this work is intended to evaluate the life cycle results for the policymakers and automobile manufacturers globally, for the emissions as well as the cost associated with each powertrain option. As an outcome of this research, several challenges are observed related to emissions and cost of the battery electric vehicles that need to be addressed before their mass adoption. Hence, the use of hybrid vehicles as a short-term solution to address the global emission reduction urgency is proposed for the road transportation sector. Which, in fact, may also be considered a long-term solution if powered with low-carbon fuels. / Tripathi, S. (2023). Life Cycle Analysis of Different Powertrain Technologies for Decarbonising Road Transportation [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/196725

Trois aspects principaux de l'imagerie fonctionnelle corps entier dans les hémopathies lymphoïdes ont été étudiés dans ma thèse. Nous avons d'abord démontré en étudiant 92 patients avec un lymphome B à grandes cellules que 14 patients (15%) considérés positifs sur l'analyse visuelle du FDG-TEP après deux cycles de chimiothérapie, auraient pu être reclassés comme des bons répondeurs si le pourcentage de réduction du SUVmax avait été mesuré. Dans un sous groupe de 80 patients, une deuxième étude a permis de montrer qu'après 4 cycles, l'analyse visuelle et l'analyse semi-quantitative SUV étaient équivalentes. Nous avons ensuite développé un protocole d'IRM fonctionnelle corps entier, utilisant une injection dynamique de Gadolinium et 5 stations d'acquisition. Cela a permis de mesurer les courbes signal-temps du rehaussement de la moelle osseuse et des lésions focales. Notre étude a permis d'optimiser un protocole d'imagerie dynamique corps entier après injection de Gadolinium, et de montrer que nous avions pu explorer avec succès 21 patients présentant un myélome multiple sous traitement, nous avons montré que cette nouvelle méthode d'IRM fonctionnelle corps entier avec injection de Gadolinium pouvait être utilisée pour évaluer la réponse du traitement. De plus, cette technique a aidé à détecter les lésions résiduelles actives de myélome après traitement alors qu'aucun signe clinique ou une immunoglobine monoclonale minime n'était présent. Le troisième aspect a été d'optimiser un protocole d'IRM fonctionnelle corps entier utilisant l'imagerie de diffusion avec asservissement respiratoire. Le but est de pouvoir mesurer le coefficient de diffusion apprent des lésions disséminées. L'étude pilote a été réalisée chez 15 patients avec un lymphome B à grandes cellules avant traitement. Nous avons aussi pu montrer les changements d'ADC après 4 cycles de chimiothérapie en considérant l'imagerie FDG-TEP/scanner comme imagerie de référence / Three components regarding whole-body functional imaging in lymphoid malignancies have been studies in this thesis. We first demonstrated retrospectively in a series of 92 patients with diffuse large B-cell lymphoma (DLBCL) that 14 patients (15%) considered as positive on visual analysis on FDG-PET after only 2 cycles of chemotherapy could have been correctly re-classified as good responders by measuring the percentage reduction of maximum standardized uptake value (SUVmax); in a subgroup of 80 patients, SUV-based assessment was equivalent to visual analysis at 4 cycles for patient outcome prediction. We secondly developed a whole-body 5-station dynamic contrast- enhanced MR protocol and time-signal intensity curves for the bone marrow and the focal lesions were successfully obtaines in 21 patients with plasma cell disorders included in the feasibility study; later in a pilot prospective study with 30 patients with multiple myeloma who received systemic therapy, we showed that this novel whole-body functional MR technique can be used to assess treatment response and helps to delect residual active disease after completion of therapy when clinically no or only minimum monoclonal protein can be identified. We thirdly optimized a whole-body diffusion-weighted MR protocol with respiratory gating in order to determine apparent diffusion coefficient (ADC) value on a whole-body scale. Pilot study was performed in 15 patients with DLBCL for both staging and response assessment at 4 cycles of chemotherapy, with FDG PET/CT as the standard of reference

Background: Amyloid transthyretin (ATTR) cardiomyopathy is caused by the deposition of misfolded proteins, known as amyloid fibrils, in the myocardium. Quantitative Single Photon Emission Computed Tomography (QSPECT) utilizing 99mTc-DPD scintigraphy has the potential to assess ATTR-suspected cardiac amyloidosis (CA). This method could offer improved risk stratification and therapy response monitoring compared to the established Perugini score system. The primary objective of this study is to evaluate the feasibility of employing a quantitative approach and correlating various parameters with LVMI (left ventricular mass index). Method: Initially, planar and volumetric sensitivity measurements were conducted, followed by verification of accuracy measurements. Several torso phantom acquisitions were then performed to evaluate the accuracy and repeatability in terms of recovery coefficient (RC) and repeatability deviation (RD). This served as the foundation for the subsequent in vivo quantification. In this retrospective study, 10 patients underwent 99mTc-DPD scintigraphy, including SPECT/CT of the thorax and echocardiography examinations, as part of a clinical routine for suspected CA. The myocardial SUVmax was determined using a semi-automatic segmentation of the entire heart, excluding the descending and ascending aortas. The bone uptake was also quantified using the SUVmean parameter within the automatically delineated volume of all bones. This enabled the determination of the normalized uptake value nSUVmax, (SUVmax to SUVmean bone). Moreover, an attempt was made to apply an automatic segmentation of the myocardium based on 26% and 36% thresholds, which were developed from the torso phantom acquisitions. This approach allowed for the utilization of the injected dose (ID). Results: The planar calibration factor (CF) exceeded the volumetric cross-calibration factor (CCF) by 3.4%. The anthropomorphic phantom exhibited an underestimation of approximately 50% in the myocardium and around 21% in the kidneys. The average RD in the myocardium and kidneys was 2.3% and 1.6%, respectively. A significant quantitative separation was observed between the ATTR and control groups, comprising 6 and 4 patients, respectively (p&lt;0.01 for SUVmax and nSUVmax, and p&lt;0.02 for SUVmean bone). Correlation analysis revealed a weak positive correlation between SUVmax and LVMI; however, the correlation was not statistically significant (ρ = 0.31, p = 0.39). The ID in the 26% and 36% threshold-based segmented myocardium showed a relatively lower negative correlation with LVMI; although this was observed in the small ATTR cohort and was not statistically significant. The latter outcome resulted from the automatic-delineation method, which was unable to segment grade 0 and 1 patients. Conclusion: This study suggests that both CFs can be used in QSPECT. The phantom measurements indicate good repeatability and a significant quantitative underestimation, primarily due to the partial volume effect (PVE). Size and shape-specific PVE corrections, encompassing various activity concentrations of myocardium-to-blood pool ratios, are essential in QSPECT of the myocardium. Moreover, quantitative SPECT/CT utilizing 99mTc-DPD scintigraphy can effectively distinguish between patients with grade 0/1 and those with grade 2/3. This approach has the potential to enhance diagnostic accuracy and improve risk stratification.

<p>&nbsp;&nbsp; Cilj ove doktorske disertacije predstavljao je ispitivanje fitohemijskog sastava i biolo&scaron;ke aktivnosti vodenih i metanolnih ekstrakata svežih i suvih plodova, kao&nbsp; i pekmeza&nbsp; pripremljenog&nbsp; po tradicionalnoj recepturi od plodova&nbsp; četiri (od kojih se jedna javlja u dve forme)&nbsp; samonike&nbsp; vrsta&nbsp; roda&nbsp; <em>Sorbus</em>&nbsp; L.:&nbsp; S.<em> aucuparia</em>, S.<em> domestica</em>, S. <em>torminalis</em>&nbsp; f.&nbsp; t<em>orminalis</em>, S. <em>torminalis</em>&nbsp; f. <em>semitorminalis</em>&nbsp; i&nbsp; S. intermedia Ispitivanje fitohemijskog sastava obuhvatalo je LC-MS/MS analizu&nbsp; 44 odabrana fenolna jedinjenja&nbsp; i&nbsp; hinske kiseline (organska&nbsp; kiselina). Takođe, spektrofotometrijski je&nbsp; određen&nbsp; sadržaj&nbsp; ukupnih fenolnih i flavonoidnih jedinjenja, kao i&nbsp; sadržaj askorbinske kiseline. Evaluacija biolo&scaron;ke aktivnosti obuhvatala je&nbsp; <em>in vitro&nbsp; </em>ispitivanja antioksidantne aktivnosti, kao i ispitivanje uticaja ekstrakata odabranih vrsta&nbsp; roda&nbsp;<em> Sorbus</em>&nbsp; na aktivnost enzima acetilholinesteraze, antimikrobni, kao i antiproliferativni potencijal.</p><p>&nbsp;&nbsp; Sumiranjem dobijenih rezultata može se zaključiti da sveži i suvi plodovi ispitivanih vrsta&nbsp; <em>Sorbus</em>,&nbsp; kao i&nbsp; pekmezi&nbsp; predstavljaju&nbsp; umeren izvor&nbsp; fenolnih jedinjenja.&nbsp; Kao najzastupljenije fenolne kiseline izdvojile su se protokatehinska i&nbsp; ferulna, a među flavonoidima amentoflavon i kvercetin-3<em>-O-</em>glukozid.&nbsp; Pored toga, hinska kiselina je zabeležena u značajnoj količini u svim analiziranim ekstraktima.</p><p>&nbsp;&nbsp;&nbsp; Ekstrakti ispitivanih vrsta pokazali su&nbsp; umeren&nbsp; antioksidantni potencijal koji se ogleda u njihovoj sposobnosti neutralizacije nekoliko radikalskih vrsta, redukcionom potencijalu i sposobnosti inhibicije lipidne peroksidacije.&nbsp; Ispitivanjem uticaja ekstrakata odabranih vrsta&nbsp;<em> Sorbus</em>&nbsp; naaktivnost&nbsp; enzima&nbsp; acetilholinesteraze&nbsp; dokazana&nbsp; je&nbsp; jedino&nbsp; umerena aktivnost&nbsp; ekstrakata vrste&nbsp; <em>S. aucuparia</em>.&nbsp; Takođe, ispitivani ekstrakti&nbsp; vrsta roda&nbsp; <em>Sorbus</em>&nbsp; ispoljili su umerenu&nbsp; antimikrobnu&nbsp; aktivnost u pogledu inhibicije&nbsp; rasta Gram pozitivne bakterije,&nbsp; <em>Staphylococcus aureus</em>, i Gram negativne bakterije,&nbsp;<em> Escherichia coli</em>.&nbsp; Vodeni i metanolni ekstrakti svežih i suvih plodova vrste&nbsp; <em>S. aucuparia</em>&nbsp; pokazali su umeren i inhibitorni potencijal prema rastu tumorskih (HeLa, MCF7, HT-29), ali i netumorskih ćelijskih linija (MRC-5).&nbsp; Rezultati dobijeni u ovoj doktorskoj distertaciji&nbsp; ukazuju na značajan&nbsp; biopotencijal plodova i pekmeza&nbsp; ispitivanih vrsta&nbsp;<em> Sorbus</em>&nbsp; i ukazuju na njihovu primenu u prehrambenoj industriji u vidu funkcionalne hrane.</p> / <p>The aim of presented&nbsp; PhD&nbsp; thesis was investigation of phytochemical composition and biological activity of water and methanol extracts of fresh and air-dried&nbsp; fruits, as&nbsp;&nbsp; well&nbsp; as&nbsp; jam,&nbsp; made according to traditional recipe,&nbsp; of fruits&nbsp; of four&nbsp; (one of them occurs in two forms)&nbsp; wild growing&nbsp; <em>Sorbus</em>&nbsp; L. species:&nbsp; <em>S. aucuparia, S. domestica, S. torminalis&nbsp; f. torminalis, S. torminalis f. semitorminalis</em> and <em>S. intermedia</em>. Examination of phytochemical composition included LC-MS/MS analysis of 44 selected phenolic compounds&nbsp; and&nbsp; quinic acid (organic acid).&nbsp; Also, total phenolic and flavonoid contents, as well as&nbsp; ascorbic acid&nbsp; content,&nbsp; were determined spectrophotometrically. Biological activity evaluation of extracts of<em>&nbsp; Sorbus</em>&nbsp; species included&nbsp;<em> in vitro&nbsp;</em> investigation of antioxidant, anti-acetylcholinesterase, antimicrobial&nbsp; and cytotoxic activity.</p><p>&nbsp;&nbsp; According to obtained results, fresh and air-dried&nbsp; fruits, as well as jam&nbsp; present&nbsp; moderate&nbsp; source of phenolic compounds. Amongs examined phenolic acids protocatechuic&nbsp; and ferulic acids were the most abundant, and amongs investigated flavonoids amentoflavone and quercetin-3-<em>O</em>-glucoside wete present in noticeable amount.&nbsp; Furthermore, high concentration of quinic acid was present in all examined extracts.</p><p>&nbsp;&nbsp; Extracts of all examined species showed&nbsp; moderate&nbsp;&nbsp; antioxidant activity in terms of radical scavenging ability, reduction potential and inhibition of lipid peroxidation.&nbsp; Also, investigation of&nbsp; anti-acetylcholinesterase activity revealed moderate activity only of extracts of <em>S. aucuparia</em>. Furthermore, examinated extracts of<em> Sorbus</em> species showedmoderate antimicrobial activity against Gram&ndash;positive bacteria, <em>Staphylococcus aureus</em>, and Gram-negative bacteria,&nbsp;<em> Escherichia coli</em>.&nbsp; In addition, water&nbsp; and methanol&nbsp; extracts of fresh and air-dried&nbsp; fruits of&nbsp;<em> S.aucuparia</em>&nbsp; showed&nbsp; inhibitory activity toward&nbsp; tumor (HeLa, MCF7, HT-29), and also non-tumor (MRC-5) cell lines. Presented results indicate significant&nbsp; biopotential of examined&nbsp; fruits of&nbsp; <em>Sorbus&nbsp;</em> species&nbsp; and&nbsp; support their use in food industry as functional food.</p>

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