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Produccao de fluor-18 em reator de pesquisa a partir de carbonato de litioGASIGLIA, HAROLDO T. 09 October 2014 (has links)
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00438.pdf: 1056627 bytes, checksum: aad5d4ec248967230e54594927266b27 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Quimica, Universidade de Sao Paulo - IQ/USP
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Efeito do pH e da concentração de fluoreto presente em dentifrícios na incorporação de fluoreto pela saliva, biofilme e fluido do biofilmeKondo, Karina Yuri [UNESP] 12 March 2013 (has links) (PDF)
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000738492.pdf: 3114256 bytes, checksum: 838875375dce954365c271d4098e4b23 (MD5) / O uso de fluoretos tem contribuído para o declínio da prevalência da cárie observado nas últimas décadas, porém um aumento na prevalência da fluorose dentária tem sido observado concomitantemente. Alternativas como a redução do pH e da concentração de fluoreto (F) dos dentifrícios têm sido estudadas na tentativa de melhorar a efetividade clínica dos mesmos, sem afetar sua eficácia anti-cárie. Considerando a escassez de estudos com metodologias in vivo avaliando a retenção intrabucal de F após a utilização de formulações aciduladas, o presente estudo avaliou a influência do pH e da concentração de fluoreto (F) de dentifrícios na retenção de F pela saliva, biofilme e fluido do biofilme. Voluntários (n=22) utilizaram dentifrícios contendo 0 (Placebo), 550 (DCRF – dentifrício com concentração reduzida de F) e 1100 ppm F (DC – dentifrício convencional), em pH 4,5 e 7,0, e escovaram seus dentes 3 vezes/dia seguindo um protocolo duplo-cego e cruzado. Amostras de saliva e biofilme dentário foram coletadas após 7 dias de uso dos dentifrícios, 1 e aproximadamente 12 horas após a última escovação. As análises de F e cálcio (Ca) foram realizadas com o eletrodo invertido após tamponamento com TISAB III e pelo método Arsenazo III, respectivamente. Os dados foram analisados por ANOVA fatorial, teste de Tukey HSD e coeficiente de correlação de Pearson (p<0,05). As concentrações de F no fluido do biofilme 1h após a escovação com o DCRF acidulado não diferiram das observadas para o DC neutro, sendo ambas significativamente mais altas que as obtidas com o placebo; este padrão, entretanto, não foi observado para o biofilme e saliva. Observou-se a ausência de um padrão definido para as concentrações de Ca nestes compartimentos, porém correlações significativas foram observadas entre as concentrações de F e Ca na saliva e no biofilme. De acordo com protocolo do estudo, concluiu-se... / The use of fluorides has contributed to the decline in caries prevalence observed in the last decades, however an increase in the prevalence of dental fluorosis has been observed concomitantly. Alternatives such as the reduction of the pH and fluoride (F) concentration of dentifrices have been studied as an attempt to improve their clinical effectiveness without affecting its anti-caries efficacy. Given the scarcity of in vivo studies assessing intraoral fluoride retention after using acidic formulations, the present study evaluated the influence of pH and F concentration of dentifrices on F uptake by saliva, biofilm and biofilm fluid. Volunteers (n = 22) used dentifrices containing 0 (Placebo), 550 (LFD – low-fluoride dentifrice) and 1100 ppm F (CD – conventional dentifrice) at pH 4.5 and 7.0, and brushed their teeth 3 times/day following a double-blind, crossover protocol. Saliva and dental biofilm samples were collected after 7 days of using the dentifrices, 1 and approximately 12 hours after last brushing. F and calcium (Ca) analysis were performed with the inverted electrode after buffering with TISAB III and the Arsenazo III method, respectively. Data were analyzed by factorial ANOVA, Tukey´s HSD test and Pearson´s correlation coefficient (p <0.05). F concentrations in the biofilm fluid 1h after brushing with acidic LFD were similar to those observed for neutral CD, both being significantly higher than values found for the Placebo; this pattern, however, was not observed for the biofilm and saliva. No defined trend was observed for Ca concentrations in these compartments, but significant correlations were observed between Ca and F concentrations in saliva and in the biofilm. According to the study protocol, it was concluded that pH influenced the uptake of F by the biofilm fluid, having little or no influence on the uptake by the biofilm and saliva, respectively.
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Produccao de fluor-18 em reator de pesquisa a partir de carbonato de litioGASIGLIA, HAROLDO T. 09 October 2014 (has links)
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Natureza e evolução dos fluidos hidrotermais nos depositos de fluorita filonar do batolito Cerro Aspero, Provincia de Cordoba, ArgentinaConiglio, Jorge Enrique 15 September 1999 (has links)
Orientador: Roberto Perez Xavier / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Geociencias / Made available in DSpace on 2018-07-25T02:06:21Z (GMT). No. of bitstreams: 1
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Previous issue date: 1999 / Resumo: Os depósitos de fluorita filonar, no setor sul das Sierras Pampeanas de Córdoba, Argentina, ocorrem em rochas cálcio alcalinas, de idade Devoniana, constituídas principalmente por biotita monzogranito porfiriticos que compõem o batólito Cerro Aspero. Os veios de fluorita são de idade Cretácea e encontram-se controlados por sistemas de falhas transcorrentes, subverticais. Além da fluorita, estes veios também estão compostos por calcedônia, localmente pirita e, eventualmente, coffinita e pitchblenda. Os veios mostram texturas típicas de preenchimento de espaços abertos (bandamento, crustificação, brechamento, geodos, etc) e estão intimamente relacionados com intensa silicificação e argilitização das rochas granítícas hospedeiras.
Três sucessivos estágios de mineralização foram distinguidos por evidências de campo, attavés da cronologia relativa de deposição de fluorita, dados de ETR e inclusões fluídas em fluorita. Estes estágios mostram geralmente padrões de ETR pouco fracionados (La/Yb= 1.4 - 14), notando-se que a distribuição dos ETR na fluorita é principalmente governada pelo fracionamento dos ETR leves. Sugere-se que a composição em ETR do fluído hidrotermal e, conseqüentemente, da fluorita, foram amplamente controlados pela diferente mobilidade dos ETR leves a depender do tipo de alteração hidrotermal. Enquanto uma lixiviação preferencial de ETR pesadas sobre ETR leves ocorreu durante a alteração silícica e argílica, nesta última, os ETR leves praticamente não foram removidos.
As temperaturas de homogeneização total de inclusões fluidas aquosas, primárias, ocorreram invariavelmente na fase liquida entre 187°C e 104°C, com concentrações de valores em tomo de 160°C, 136°C e 116°C (estágios 1, 11 e III, respectivamente), definindo uma marcante tendência de resfriamento da solução. Este resfriamento está associado com importantes variações na fOz do fluido, de oxidante a redutor, inferido a partir da relação Eu/Eu* e da assembléia mineral (pirita, pitchblenda e coffmita). As inclusões aquosas nestes três estágios de deposição de fluorita mostram temperaturas de fusão do gelo no intervalo entre -O,3°C - +0,4°C, indicando que o fluido mineralizante sempre manteve uma salinidade muito baixa, próxima a água pura. Não foram encontradas evidencias de ebulição nem mistura de fluidos. Os dados de inclusões fluidas sugerem que os três estágios de mineralização propostos foram o resultado de um único e progressivo evento hidrotermal e suportam um reservatório único e uniforme para as soluções mineralizantes, provavelmente de águas meteóricas aquecidas e não de fluidos gerados em zonas mais profundas da crosta / Abstract: Vein-type fluorite deposits in the southem part of the Sierras Pampeanas, Córdoba, Argentina, occur mainly hosted by caleaIkaline porphyritie biotite granites, whieh belong to the Paleozoie, post-tectonie Cerro Aspero batholith. The fluorite veins, of Cretaceous age, occupy steep / Mestrado / Metalogenese / Mestre em Geociências
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Estudo "in vitro" do bochecho pre-escovação plax na reatividade do fluor com esmalte dental humanoFranco, Eliane Melo 16 July 2018 (has links)
Orientador : Jaime A. Cury / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-16T02:04:29Z (GMT). No. of bitstreams: 1
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Previous issue date: 1992 / Resumo: Trabalhos da Iitera tura tem mostrado que o detergente lauril sulfato de s6dio (L.S.S.) inibe a reatividade do flúor com
o esmalte dental humano. A eficiência clínica do bochecho pré-escovação PLAX@ em termos de melhorar a remoção mecânica da placa contém tem sido questionada. Considerando que este bochecho L.S.S. como um dos ingredientes ativos o objetivo do
presente trabalho foi estudar sua interferência na reatividade do flúor iônico (F-) e ionizável (MFP) com o esmalte dental humano,
na ausência e presença de saliva. Para tal fim foram utilizados partículas de esmalte dental humano pré-tratado ou não com PLAX@ e submetidas a reaçãd com soluções contendo 250 ppmF na forma de NaF ou MFP e na ausência ou presença de saliva. Apos reação de 1 min, foram determinadas no esma Ite as concentrações de fi úor total (FT), fluoreto de cálcio (CaF2) e apatita fluoretada (AF). Os resultados obtidos mostraram que o PLAX@ inibiu a reatividade tanto ~o F- como do MFP com esmalte dental e que a % de inibição aumenta para o F- na presença de saliva, porém diminui com reIação ao MFP. Conclui-se que o bochecho pré-escovação inibe in vitro a reatividade do flúor com esmalte dental humano, justificando a necessidade de estudo final / Abstract: Studies have indicated that sodium lauryl sul'fate (S.L.S.) may reduced the 'fluoride uptake by enamel. The
prebrushing rinse (PLAX@) has S.L.S. and 'furthermore his plaque removal has been questioned. So, the aim o'f this in vi tro
study was evaluate the e'f'fecto'f this rinse on 'fluoride uptake on enamel 'from NaF (F-) and MFP solutions, in sal iva presence or
abscence. Human enamel powder pretreated or not with PLAX@ were exposed to either an aqueous solution o'f 250 ppmF as NaF or MFP. water ( 10m I ) time and was 1 min 'followed by washing in.The exposure deionized methanol ( 10ml ) . The amounts o'f total 'fI u o r i de, a I k a I i s b I u b I e ( Ca F 2 ) a n d 'fi r m i I Y b o u n d 'fI u o r i d e ( F A ) on enamel were determined with ion speci'fic electrode ORION 96-09. The resuIts showed that PLAX@ reduced the 'fIuoride uptake o'f both CaF 2 and FA on enamel 'from NaF or MFP solutions. The percentage o'f inhibition increased in sal iva presence 'for NaF; but decreased 'for MFP. It was conclued that the prebrushing rinse inhibits in vitro the 'fluoride reactivity with enamel, justi'fying an in vivo study / Mestrado / Farmacologia / Mestre em Odontologia
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Využití fluoralkylových hypervalentních sloučenin jódu v C-H funkcionalizaci malých molekul a aromatických aminokyselinových zbytků / Application of fluoroalkyl hypervalent iodine reagents in C-H functionalization of small molecules and aromatic amino acid residuesRahimidashaghoul, Kheironnesae January 2021 (has links)
The chemistry of fluorolkyl hypervalent iodine reagents has witnessed a great boast in recent years. These compounds are highly attractive as drug candidates, advanced materials and agrochemicals as described in detail in the Introduction. Despite this fact, applications of these reagents in biological studies are rather rare and under developed. The goal of this thesis is therefore the development of mild and metal-free methods in order to fill this gap. Two ways of application of fluoroalkyl hypervalent iodine reagents in labeling of biologically relevant compounds was explored. First, the applicability of previously reported parent Togni CF3 and their analogous tetrafluoroethyl reagents in radical fluoroalkylation of electron-rich substrates such as indole and pyrrole derivatives using sodium ascorbate as reductant was described. This afforded trifluoromethyl or 1,1,2,2-tetrafluoroethyl containing products in moderate to high yields. Next, same reagents were applied for labeling of several peptides and proteins bearing aromatic amino acids in their structure. This way, peptides and proteins containing electron-rich aromatics such as Trp, Phe, Tyr and His were reacted with fluoroalkyl groups with high selectivity toward Trp. In the second part of the work, a different approach of radical...
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Synthèse d’α-C-galactosylcéramides difluorés et évaluation de leurs propriétés immunorégulatrices pour le traitement des maladies autoimmunes systémiques / Synthesis of difluorinated α-C-galactosylceramides and assessment of their immunoregulation properties for the treatment of systemic autoimmune diseasesColombel, Sophie 18 October 2012 (has links)
Les O-glycoconjugués et les dérivés glycosidiques sont des composés naturels impliqués dans de nombreux processus biologiques. Cependant, leurs propriétés sont grévées par la médiocre stabilité in vivo de la liaison osidique. Il est donc intéressant de développer des mimes non hydrolysables. Nous nous sommes intéressés au remplacement de l'oxygène anomérique par un groupement gem-difluorométhylène.La synthèse d'analogues difluorés d'α-galactosylcéramides avec diverses longueurs de chaînes grasses est décrite dans ce travail. La partie C-glycosidique de ces molécules est construite par l'application d'une séquence d'addition radicalaire et de réduction diastérosélective. La chaîne phytosphingosine est introduite par le synthon α-CF₂-galactose via un transfert de l'O-2 au carbone pseudo-anomérique, puis un couplage peptidique permet de former la partie céramide. Quatre analogues possédant diverses chaînes phytosphingosines (C₅H₁₁, C₂₄H₄₉) et divers acides gras (C₇H₁₅, C₁₅H₃₁ et C₂₅H₅₁) ont été synthétisés et évalués biologiquement. / O-glycoconjugates and carbohydrate-based molecules are natural compounds implied in many biological processes. However, their properties are burdened by the low in vivo stability of the osidic bond. It is thus interesting to develop non hydrolizable mimetics. We were interested in the replacement of the anomeric oxygen by a gem-difluoromethylene group.The synthesis of difluorinated α-galactosylceramides featuring various lipidic chain lenghts is described herein. The C-glycosidic part of these molecules is construted by a sequence of radical addition and diastereoselective reduction. The phytosphingosine chain is introduced on this intermediate by an O-2 to C-1' migration and the ceramide synthesis is completed by a petidic coupling. Four analogues featuring various phytosphingosines chains (C₅H₁₁, C₂₄H₄₉) and fatty acids (C₇H₁₅, C₁₅H₃₁ et C₂₅H₅₁) were synthetized and biologically assessed.
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Pseudopeptides à motif fluorooléfine : conception, synthèse, distérosélective et évaluation biologique et structurale / Stereocontrolled synthesis of functionalized fluorinated alkenes : conception, synthesis and biological evaluation of fluorinated pseudopeptidesPierry, Camille 23 November 2010 (has links)
L’intérêt des composés organiques fluorés est de nos jours de plus en plus important en raison de leur large domaine d’application. Par exemple, dans le domaine de la chimie médicinale, la présence d’un atome de fluor altère sensiblement les propriétés physicochimiques des molécules et permet très souvent une amélioration de leur profil thérapeutique.Dans ce contexte, notre laboratoire s’intéresse au développement de nouveaux fluoropeptidomimétiques dans le but de pallier les différents problèmes associés aux peptides (pauvre biodisponibilité, flexibilité conformationnelle). Parmi les différents peptidomimétiques connus, le motif fluorooléfine (CF=CH) peut être considéré comme unisostère de la liaison peptidique du à ses similarités stériques et électroniques.Dans le but de proposer un mode d’accès général aux pseudopeptides fluorés comportant une fluorooléfine à la place du lien peptidique, nous avons développé une nouvelle stratégie basée sur une étape d’addition nucléophile de réactifs organométalliques sur des N-(tertbutanesulfinyl)-a-fluoroénimines chirales. Cette méthodologie nous permet de contrôler le centre asymétrique du côté N-terminal du peptide.Nous avons ensuite appliqué cette stratégie à la synthèse de composés biologiquement actifs tels que le 26RFa, un neuropeptide impliqué dans le contrôle et la régulation de la prise alimentaire. Dans ce contexte, plusieurs dipeptides fluorés ont été synthétisés puis incorporés au sein de l’heptapeptide qui ont donné lieu à des études de relations structureactivité. / Fluoroorganic compounds are increasingly popular owing to their wide range of biological applications. For example, in the field of medicinal chemistry, fluorinated molecules clearlyalter physicochemical properties compared to non-fluorinated derivatives, and often with animproved therapeutic profile.In this context, our laboratory is interested in the development of new fluoropeptidomimetics aiming at circumventing common problems associated with peptides(poor bioavaibility, flexibility). For this purpose, the fluoroolefin moiety (CF=CH) can act as aneffective peptide bond mimic due to steric and electronic similarities.In our project aiming at proposing general synthesis methods of fluorinated pseudopeptides featuring a fluoroolefin moiety as the peptide bond analogue, we develop a new strategy based on nucleophilic addition of organometallic reagents to chiral N-(tert-butanesulfinyl)-a-fluoroenimines. This methodology allows us to control the asymmetric center on the Nterminalside of the peptide.Then, we applied our strategy to the synthesis of biologically active compound such as the26RFa, a neuropeptide involved in regulation and food intake. In this context, several fluorinated dipeptides have been synthesized and incorporated into the natural heptapeptide for a structure-activity relationship study.
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N-fluoroalkyles et CF3-cyclopropanes; vers de nouvelles unités peptidomimétiques / N-fluoroalkyls and CF3-cyclopropanes; new peptidomimétics unitsMamone, Marius 03 December 2015 (has links)
Grâce à des propriétés physico-chimiques particulières, le fluor prend de plus en plus d’importance dans la chimie médicinale et plus particulièrement dans les peptidomimétiques. Dans ce mémoire, deux classes de peptidomimétiques fluorées ont été étudiées.Dans la première partie, de nouveaux groupements N-Rf ; les hydrazines difluoro ou trifluorométhylées et les 1,2,3 triazoles N-difluorométhylés ont été préparés et des études de leurs propriétés structurales ont montré l’intérêt de l’incorporation du fluor sur la conformation des pseudopeptides via des interactions NH-F.Dans la seconde partie, de nouveaux peptidomimétiques comportant des groupements cyclopropanes trifluorométhylés ont été conçus et synthétisés en tant qu’inhibiteurs potentiels du protéasome 26S (un macro-complexe protéique impliqué dans la dégradation de nombreuses protéines intracellulaires et qui a fait ses preuves en tant que cible pour le traitement de cancers). / Through special physico-chemical properties, fluorine is becoming increasingly important in medicinal chemistry and particularly in peptidomimetics. In this paper, two classes of fluorinated peptidomimetics were studied.In the first part, new N-Rf moieties; difluoro or trifluoromethylated hydrazines and N-difluoromethyl 1,2,3 triazoles were prepared and the study of their structural properties have shown the benefit of the incorporation of fluorine on the conformation of the peptidomimetics via NH-F interactions.In the second part, new trifluoromethylated cyclopropanes containing peptidomimetics were designed and synthesized as potential inhibitors of the 26S proteasome, a macro-complex protein involved in the degradation of many intracellular proteins and which has been recognized as a target for cancer treatment.
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Hardware- und Methodenentwicklung für die 23Na- und 19F-Magnetresonanztomographie / Hardware and method development for 23Na and 19F magnetic resonance imagingLykowsky, Gunthard January 2019 (has links) (PDF)
Neben dem Wasserstoffkern 1H können auch andere Kerne für die Magnetresonanztomographie (MRT) genutzt werden. Diese sogenannten X-Kerne können komplementäre Informationen zur klassischen 1H-MRT liefern und so das Anwendungsspektrum der MRT erweitern. Die Herausforderung bei der X-Kern-Bildgebung liegt zum großen Teil in dem intrinsisch niedrigen Signal-zu-Rauschen-Verhältnis (SNR), aber auch in den spezifischen Kerneigenschaften. Um X-Kern-Bildgebung optimal betreiben zu können, müssen daher Sende-/Empfangsspulen, Messsequenzen und -methoden auf den jeweiligen Kern angepasst werden. Im Fokus dieser Dissertation standen die beiden Kerne Natrium (23Na) und Fluor (19F), für die optimierte Hardware und Methoden entwickelt wurden.
23Na spielte in dieser Arbeit vor allem wegen seiner Funktion als Biomarker für Arthrose, einer degenerativen Gelenkserkrankung, eine Rolle. Hierbei ist insbesondere die quantitative Natriumbildgebung von Bedeutung, da sich mit ihr der Knorpelzustand auch im Zeitverlauf charakterisieren lässt. Für die quantitative Messung mittels MRT ist die Kenntnis des B1-Feldes der eingesetzten MR-Spule entscheidend, denn dieses kann die relative Signalintensität stark beeinflussen und so zu Fehlern in der Quantifizierung führen. Daher wurde eine Methode zur Bestimmung des B1-Feldes untersucht und entwickelt. Dies stellte aufgrund des niedrigen SNR und der kurzen sowie biexponentiellen T2-Relaxationszeit von 23Na eine Herausforderung dar. Mit einer retrospektiven Korrekturmethode konnte eine genaue und zugleich schnelle Korrekturmethode gefunden werden.
Für die 1H- und 23Na-Bildgebung am menschlichen Knieknorpel wurden zwei praxistaugliche, doppelresonante Quadratur-Birdcage-Resonatoren entwickelt, gebaut und charakterisiert. Der Vergleich der beiden Spulen bezüglich Sensitivität und Feldhomogenität zeigte, dass der Vier-Ring-Birdcage dem Alternating-Rungs-Birdcage für den vorliegenden Anwendungsfall überlegen ist. Die in vivo erzielte Auflösung und das SNR der 23Na-Bilder waren bei beiden Spulen für die Quantifizierung der Natriumkonzentration im Knieknorpel ausreichend. Hochauflösende anatomische 1H-Bilder konnten ohne Mittelungen aufgenommen werden.
In einer umfangreichen Multiparameter-MR-Tierstudie an Ziegen wurde der Verlauf einer chirurgisch induzierten Arthrose mittels 23Na- und 1H-Bildgebungsmethoden untersucht. Hierbei kamen dGEMRIC, T1ρ-Messung und quantitative Natrium-MRT zum Einsatz. Trotz des im Vergleich zum Menschen dünneren Ziegenknorpels, der niedrigen Feldstärke von 1,5 T und den auftretenden Ödemen konnten erstmals diese MR-Parameter über den Studienverlauf hinweg an den gleichen Versuchstieren und zu den gleichen Zeitpunkten ermittelt werden. Die Ergebnisse wurden verglichen und die ermittelten Korrelationen entsprechen den zugrundeliegenden biochemischen Mechanismen. Die im Rahmen dieser Studie entwickelten Methoden, Bildgebungsprotokolle und Auswertungen lassen sich auf zukünftige Humanstudien übertragen.
Die mit klinischen Bildgebungssequenzen nicht zugängliche kurze Komponente der biexponentiellen T2*-Relaxationszeit von 23Na konnte mittels einer radialen Ultra-Short-Echo-Time-Sequenz bestimmt werden. Hierzu wurde eine Multi-Echo-Sequenz mit einem quasizufälligen Abtastschema kombiniert. Hierdurch gelang es, die kurze und lange T2*-Komponente des patellaren Knorpels in vivo zu bestimmen.
19F wird in der MRT wegen seiner hohen relativen Sensitivität und seines minimalen, körpereigenen Hintergrundsignals als Marker eingesetzt. Zur Detektion der niedrigen in-vivo-Konzentrationen der Markersubstanzen werden hochsensitive Messspulen benötigt.
Für die 19F-Bildgebung an Mäusen wurde eine Birdcage-Volumenspule entwickelt, die sowohl für 19F als auch 1H in Quadratur betrieben werden kann, ohne Kompromisse in Sensitivität oder Feldhomogenität gegenüber einer monoresonanten Spule eingehen zu müssen. Dies gelang durch eine verschiebbare Hochfrequenzabschirmung, mit der die Resonanzfrequenz des Birdcage verändert werden kann. Es konnte weiterhin gezeigt werden, dass die Feldverteilungen bei 1H und 19F im Rahmen der Messgenauigkeit identisch sind und so der 1H-Kanal für die Pulskalibrierung und die Erstellung von B1-Karten für die 19F-Bildgebung genutzt werden kann. Hierdurch kann die Messzeit deutlich reduziert werden.
Ein grundsätzliches Problemfeld stellt die Korrelation unterschiedlicher Bildgebungsmodalitäten dar. In der MRT betrifft das häufig die Korrelation von in-/ex-vivo-MR-Daten und den dazugehörigen Lichtbildaufnahmen an histologischen Schnitten. In dieser Arbeit wurde erstmals erfolgreich eine 1H- und 19F-MR-Messung an einem histologischen Schnitt vorgenommen. Durch die Verwendung einer optimierten 1H/19F-Oberflächenspule konnte die 19F-Signalverteilung in einer dünnen Tumorscheibe in akzeptabler Messzeit aufgenommen werden. Da der gleiche Schnitt sowohl mit Fluoreszenzmikroskopie als auch mit MRT gemessen wurde, konnten Histologie und MR-Ergebnisse exakt korreliert werden.
Zusammenfassend konnten in dieser Arbeit durch Hardware- und Methodenentwicklung zahlreiche neue Aspekte der 19F- und 23Na-MRT beleuchtet werden und so zukünftige Anwendungsfelder erschlossen werden. / In addition to the hydrogen nucleus 1H, other nuclei can also be used for magnetic resonance imaging (MRI). These so-called X-nuclei can provide complementary information on classical 1H MRI and thus expand the range of applications of MRI. The challenge in X-nucleus imaging is largely due to the intrinsically low signal-to-noise ratio (SNR), but also to the specific properties of the nucleus. In order to optimally perform X-nuclei imaging, transmit/receive coils, imaging sequences and methods must be adapted to the respective nucleus. The two nuclei sodium (23Na) and fluorine (19F) were in the focus of this dissertation and thus optimized hardware and methods were developed for these nuclei.
23Na played a major role in this work, mainly because of its function as a biomarker of osteoarthritis, a degenerative joint disease. In particular, the quantitative sodium imaging is of importance, as it can characterize the cartilage state over time. For quantitative measurements by MRI, the knowledge of the B1 field of the MR coil used is crucial, because this can strongly influence the signal intensity and thus lead to errors in the quantification. Therefore, a method for the determination of the B1 field was developed. This presented a challenge due to the low SNR and the short and biexponential T2 relaxation time of 23Na. Using a retrospective correction method, a precise and at the same time rapid correction method could be found.
Two practicable double resonant quadrature birdcage resonators have been developed, constructed and characterized for 1H/23Na imaging on human knee cartilage. The comparison of the two coils in terms of sensitivity and field homogeneity showed that the four-ring birdcage is superior to the alternating-rungs birdcage for the present application. The in vivo resolution and SNR of the 23Na images were sufficient for both coils to quantify the sodium concentration in the knee cartilage. High-resolution 1H anatomical images could be acquired without averaging.
In a large multiparameter MRI animal study on goats, the progression of surgically induced osteoarthritis was studied using 23Na and 1H imaging techniques. DGEMRIC, T1ρ and quantitative sodium MRI were used. Despite thinner goat cartilage compared to humans, low field strength of 1.5 T and the occurring edema, it was possible for the first time to determine these MR parameters over the course of the study on the same experimental animals and at the same time points. The correlations of the MR parameters correspond to the underlying biochemical mechanisms. The methods, imaging protocols and evaluations developed in this study can be applied to future human studies.
The short component of the biexponential T2* relaxation time of 23Na, which is not accessible with clinical imaging sequences, could be determined by means of a radial ultra-short echo time sequence. For this purpose, a multi-echo sequence was combined with a quasi-random sampling scheme. This enabled the determination of the short and long T2* component of patellar cartilage in vivo.
19F is used as a marker in MRI because of its high relative sensitivity and minimal body’s own background signal. To detect the low in vivo concentrations of the marker substances, highly sensitive measuring coils are required. For 19F imaging of mice, a birdcage volume coil was developed that can be operated in quadrature for both 19F and 1H without compromising sensitivity or field homogeneity compared to monoresonant coils. This is due to a slidable RF shield, which is used to change the resonance frequency of the birdcage. It has also been shown that field distributions at 1H and 19F are identical allowing the 1H channel to be used for pulse calibration and B1 mapping for 19F imaging. This can significantly reduce the acquisition time.
A fundamental challenge is the correlation of different imaging modalities. In MRI, this often affects the correlation of in and ex vivo MR data and the associated images of histological sections. In this work, 1H and 19F MR measurements of a histological section were successfully performed for the first time. By using an optimized 1H/19F surface coil, the 19F signal distribution in a thin tumor slice was acquired within an acceptable acquisition time. Since the same section was measured by fluorescence microscopy as well as by MRI, histology and MR results could be correlated exactly.
In summary, hardware and method development in this work has highlighted numerous new aspects of 19F and 23Na MRI, opening up future fields of application.
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