No description available.

Reproduction de : Thèse d' exercice : Médecine spécialisée : Nancy 1 : 2002. / Thèse : 2002NAN11141. Titre provenant de l'écran-titre.

The study was conducted to develop a technique that measures the amount of gadolinium based contrast agent accumulated in a head tumour by x-ray fluorescence, while a patient is exposed to neutrons or during external beam radiotherapy planning. In this research, measurements of the gadolinium concentration in a vessel simulating a brain tumour located inside a head phantom, by the x-ray fluorescence method were taken, where the Magnevist contrast medium which has gadolinium atom, in the tumour vessel, was excited by a 36 GBq (0.97 Ci) 241Am source that emits gamma rays of 59.54 keV, in 35.7 % of it’s decays, resulting the emission of characteristic fluorescence of gadolinium at 42.98 keV that appeared in the X-ray fluorescence spectrum. A Cadmium Telluride (CdTe) detector was used to evaluate and make an analysis of the gadolinium concentration. Determinations of the gadolinium content were obtained directly from the detector measurements of XRF from gadolinium in the exposed tumour vessel. The intensity measured by the detector was proportional to the gadolinium concentration in the tumour vessel. These concentrations of gadolinium were evaluated for dose assessment. The positioning of the head phantom was selected to be in the lateral and vertex positions for different sizes of tumour vessels. Spherical tumour vessels of 1.0, 2.0, 3.0 cm and an oval tumour vessel of 2.0 cm diameter and 4.0 cm length, containing the gadolinium agent, contained concentration between 5.62 to 78.63 mg/ml. They were placed at different depths inside a head phantom at different positions in front of the detector and the source for the measurements. These depths ranged from 0.5 cm to 5.5 cm between the center of the tumour and interior wall of the head phantom surface. The total number of measurements in all four sizes of the tumour vessel was 478; 78 examinations of a 1.0 cm spherical tumour vessel, 110 examinations of a 2.0 cm spherical tumour vessel, 150 examinations of a 3.0 cm spherical tumour vessel and 140 examinations of a 2.0 x 4.0 cm ellipsoid tumour vessel. To measure the size and the shape of the tumour by the alternative radiographic method, a general x-ray machine with radiograph film was used. Based on that, the appropriate shape of concentration could be selected for therapy. The differences of optical density in the x-ray films showed that the noise was increased with low concentration of the Gd. Because radiographic film may be subjected to different chemical processes where the darkness will be affected, these measurements would be very hard to be quantitative. Accordingly it is difficult to use the film for Gd concentrations. The obtained data show that the method works very well for such measurements.

The study was conducted to develop a technique that measures the amount of gadolinium based contrast agent accumulated in a head tumour by x-ray fluorescence, while a patient is exposed to neutrons or during external beam radiotherapy planning. In this research, measurements of the gadolinium concentration in a vessel simulating a brain tumour located inside a head phantom, by the x-ray fluorescence method were taken, where the Magnevist contrast medium which has gadolinium atom, in the tumour vessel, was excited by a 36 GBq (0.97 Ci) 241Am source that emits gamma rays of 59.54 keV, in 35.7 % of it’s decays, resulting the emission of characteristic fluorescence of gadolinium at 42.98 keV that appeared in the X-ray fluorescence spectrum. A Cadmium Telluride (CdTe) detector was used to evaluate and make an analysis of the gadolinium concentration. Determinations of the gadolinium content were obtained directly from the detector measurements of XRF from gadolinium in the exposed tumour vessel. The intensity measured by the detector was proportional to the gadolinium concentration in the tumour vessel. These concentrations of gadolinium were evaluated for dose assessment. The positioning of the head phantom was selected to be in the lateral and vertex positions for different sizes of tumour vessels. Spherical tumour vessels of 1.0, 2.0, 3.0 cm and an oval tumour vessel of 2.0 cm diameter and 4.0 cm length, containing the gadolinium agent, contained concentration between 5.62 to 78.63 mg/ml. They were placed at different depths inside a head phantom at different positions in front of the detector and the source for the measurements. These depths ranged from 0.5 cm to 5.5 cm between the center of the tumour and interior wall of the head phantom surface. The total number of measurements in all four sizes of the tumour vessel was 478; 78 examinations of a 1.0 cm spherical tumour vessel, 110 examinations of a 2.0 cm spherical tumour vessel, 150 examinations of a 3.0 cm spherical tumour vessel and 140 examinations of a 2.0 x 4.0 cm ellipsoid tumour vessel. To measure the size and the shape of the tumour by the alternative radiographic method, a general x-ray machine with radiograph film was used. Based on that, the appropriate shape of concentration could be selected for therapy. The differences of optical density in the x-ray films showed that the noise was increased with low concentration of the Gd. Because radiographic film may be subjected to different chemical processes where the darkness will be affected, these measurements would be very hard to be quantitative. Accordingly it is difficult to use the film for Gd concentrations. The obtained data show that the method works very well for such measurements.

L’objectif poursuivi au cours de ce travail est l’encapsulation de complexes métalliques au sein de nanoparticules biocompatibles, et ce pour des visées diagnostiques. Dans ce but, un protocole de double émulsion-diffusion de solvant Wi/O/We, n’utilisant que des composés biocompatibles, a été mis au point et optimisé pour obtenir, de façon quantitative et reproductible, des nanoparticules de PLGA de diamètre compatible avec une injection par voie parentérale. Cette formulation a été employée avec succès pour l’encapsulation de complexes modèles de Cu(II). Les formulations optimales permettent d’obtenir des nanoparticules possédant des diamètres hydrodynamiques moyens inférieurs à 200 nm avec des efficacités d’encapsulation entre 20 et 25 %. L’utilisation de cette formulation pour l’encapsulation de chélates de gadolinium ne permet pas d’obtenir des rendements d’encapsulation satisfaisants. La modification du protocole vers une méthodologie Wi/O1/O2ne permet pas d’améliorer l’encapsulation et dénote l’absence d’affinités entre le polymère hydrophobe et les complexes hydrophiles. L’utilisation de nanoparticules composées d’une matrice hydrophile permet d’obtenir des taux de charges nettement supérieurs. Ceci conforte l’hypothèse selon laquelle les interactions entre le complexe et la matrice des nanoparticules jouent un rôle crucial pour l’encapsulation. / The goal of this work was to encapsulate metal complexes into biocompatible nanoparticles for diagnostics. To reach this purpose, a double emulsion-solvent diffusion Wi/O/We technique was optimized, using only biocompatible compounds. It allowed the obtention of PLGA nanoparticles that are compatible with parenteral injections in a reproducible and quantitative way. This formulation was successfully applied to encapsulate model Cu(II)complexes. Optimal formulations showed mean diameters below 200 nm with encapsulation yields in the 20-25 % range. The use of this formulation for gadolinium chelates did not lead to satisfactory encapsulation yields. Thereafter, a Wi/O1/O2 methodology was developed but could not allow to raise the encapsulation efficiencies. This point showed the lack of affinity between the hydrophobic polymer and the hydrophilic chelates. The use of nanoparticles made of an hydrophilic matrix showed a ten-fold increase in the drug loading efficiency. This confirms the hypothesis in which interactions between chelates and nanoparticle matrices play a crucial role for encapsulation.

L'imagerie par résonance magnétique est une des méthodes de diagnostic les plus utilisées, aussi bien dans le domaine médical que dans les études précliniques. Cependant, la relaxivité des agents de contraste commerciaux ne représente qu'une fraction de la relaxivité prédite par la théorie et il est nécessaire d'optimiser les différents paramètres dont elle dépend pour atteindre des valeurs de relaxivité plus élevées : nombre de molécules d'eau en première sphère de coordination, vitesse d'échange de l'eau, dynamique de rotation du complexe, relaxation électronique, distance Gd(III)-proton. Dans ce travail, nous présentons la synthèse, la stabilité et la relaxivité des complexes de Gd(III) de deux séries de ligands tripodes dérivés de la 8-hydroxyquinoléine, basés l'une sur une plateforme 1,4,7 triazacyclononane, l'autre sur un pivot azote central. Ces complexes ont montré des stabilités comparables à celles des agents commerciaux, des valeurs de relaxivités élevées dans l'eau ainsi qu'en milieu biologique. L'utilisation de la 8-hydroxyquinoléine comme base des ligands a permis de sensibiliser le Nd(III) et l'Yb(III) pour la luminescence proche infrarouge, ouvrant la possibilité pour le développement de nouveaux systèmes bimodaux. / Magnetic resonance imaging is a commonly used diagnostic method in medicinal practice as well as in biological and preclinical research. However, the relaxivity of commercial contrast agents is only a few percent of the theoretically predicted relaxivity. An optimisation of the different parameters who have an impact on the relaxivity (number of gadolinium bound water molecules, water exchange rate, rotation dynamic of the complex, electronic relaxation, Gd(III)-proton distance) is needed to obtain higher relaxivities. In this work, we present the synthesis, the stability and the relaxivity of the Gd(III) complexes of two series of 8-hydroxyquinolinate-based ligands, one using a 1,4,7 triazacyclononane platform, the other one using a central nitrogen architecture. Theses complexes show stabilities comparable to commercial agents, and high relaxivities in both water and serum. The 8-hydroxyquinolinate moiety allows these ligands to sensitize Nd(III) and Yb(III) for Near Infra Red (NIR) luminescence, leading to a new class of potential bimodal systems.

Inledning: Det finns anledning att tro att antalet undersökningar med gadoliniumbaserade kontrastmedel ökar i takt med tiden och i samband med detta en ökning av akuta och sena biverkningar. Syfte: Syftet med denna litteraturöversikt var att identifiera olika typer av biverkningar som kan orsakas av gadoliniumbaserade kontrastmedel (GBKM), att undersöka dess incidens, samt att identifiera eventuella riskgrupper. Dessa tre huvudkategorier ansågs vara de mest relevanta för sammankopplandet av problemets olika delar och ursprung. Metod: Denna studie genomfördes som en allmän litteraturöversikt där endast kvantitativa vetenskapliga artiklar ingick. Resultat: Resultatet påvisade att risken för att drabbas av akuta och sena biverkningar efter injektion av gadoliniumbaserade kontrastmedel är låg (under 0,5%) och att flertalet av dessa är milda biverkningar. Kvinnor representerade det största antalet rapporterade fall i de flesta studier och risken för biverkningar ökade dessutom om historik av allergier och tidigare biverkningar fanns. Slutsats: Genom denna litteraturstudies resultat kunde vi som slutsats framhäva att även om förekommande incidens och risk för biverkningar av gadoliniumbaserade kontrastmedel var låg, så rapporteras mer eller mindre allvarliga fall löpande. Det gör det rimligt att anta att röntgensjuksköterskan under sitt arbetsliv kommer att få uppleva en eller flera situationer där hon eller han måste besitta kunskap och kännedom om säkerhetsrutiner vid ett tillbud. Förutom röntgensjuksköterskans upprätthållande i kunskap om ämnet, så ses dialogen som förs mellan patient och personal viktig, där all information av vikt tolkas och behandlas på rätt sätt.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 144-158). Available also in a digital version from Dissertation Abstracts.

Magnetic Resonance Spectroscopy (MRS) for the evaluation of in vivo cerebral metabolite ratios is a relatively new radiological modality, which permits the detection and evaluation of specific metabolites within the human body. As with all imaging modalities, the accuracy of the equipment to perform its given task is paramount and the effect of introduction of elements and/or contrast agents to a study, must be understood before a diagnosis or prognosis can be made with any degree of certainty. The following chapters describe the development and testing of a phantom, the development and testing of metabolite simulating solutions and the experiments conducted to determine the spatial localisation accuracy of a MRS imaging system. This thesis begins with a description of the steps undertaken to investigate a clinical MRS system's capacity to reliably produce spectra over both the long and short term. Validation of the phantom construction, metabolite simulating solutions and spatial localisation accuracy is presented in detail. The construction of the localisation phantom resulted in a two compartment perspex phantom and the development of the aqueous metabolite solutions produced two solutions with distinct and separate metabolite peaks with comparable peak amplitudes and sufficient line width separation to prevent possible metabolite resonance cross contamination but without illustrating any significant susceptibility artefacts. Development of the metabolite simulating solutions was a major part of the work conducted. Short and long term (1 year) reproducibility of the measured metabolite peak amplitudes were assessed for four different pulse sequences. Of these, the most reproducible results were obtained with a TE 270ms PRESS sequence (coefficient of variation < 0.6% (short term) and < 3% (long term)). The spatial localisation experiments illustrated a disturbing error in the placement of the user prescribed volume of interest (VOI) with respect to the actual VOI acquisition with a difference between the two volumes of interest of up to 3 mm or 15% of the VOI size in two axes. Possible effects of magnetic resonance imaging contrast agents, specifically Gd-DTPA were also investigated. Fifty patients were included in this study. The metabolic peak amplitudes were measured pre and post-administration of the contrast agent for each subject. A paired t-test demonstrated that there was no significant difference between the mean peak heights pre- and post- administration (0.07 < p < 0.9 for the various peak amplitudes measured).

Zugl.: Saarbrücken, Univ., Diss., 2003