Diplomová práce je zaměřena na studium degradace kontrastních látek pro magnetickou rezonanci. Tyto látky se dnes ve velké míře používají v oblastech s rozvinutým zdravotnictvím. Můžeme je najít v odtocích z čistíren odpadních vod, což svědčí o tom, že běžné stupně čištění odpadních vod nejsou dostatečně efektivní pro jejich odstranění. O degradaci kontrastních látek na bázi gadolinia je jen málo informací. Fotokatalytický rozklad za pomoci oxidu titaničitého a také ozonace vybrané kontrastní látky gadobutrolu, byl sledován pomocí měření celkového organického uhlíku, mikroskopie termálních čoček a spektrofotometrie.

The upward trend in internal combustion engine efficiency is likely driven by the depletion of fossil fuels. Since no replacement in sight can deliver energy comparable to the conventional oil, there is a need to use it more rationally and effectively. Thermal barrier coatings have been seen for a long time as a solutionto increase the thermal efficiency of gas turbine engines but suffer from the lackof strong applicability in internal combustion engines. This is due to the different restrictions when comparing the environment on the gas turbines and in internal combustion engines. To overcome this problem and, at the same time, expand the application field of thermal barrier coatings, more efforts need to be devoted.In this work, different top coat materials using various deposition techniques were evaluated and categorized in three different thermal barrier coating (TBC) architectures. The first was the lamellar yttria-stabilized zirconia (YSZ) top coat deposited by atmospheric plasma spray (APS), used as a reference sample. The second architecture was a columnar suspension plasma spray (SPS) TBC with YSZ and gadolinium zirconate (GZO) top coat. The SPS process can produce avariety of microstructures, and they were, for the first time, tested in an internal combustion engine. The third architecture was an SPS top coat, with an additional layer on the top, called a sealing layer of either metallic or ceramic material, both never investigated in a diesel engine application earlier. For the thermophysical properties investigation, a combination of laser flashanalysis (LFA) and modeling with object-oriented finite element (OOF) was employed to understand the properties in all the applications. The performance of the coatings was evaluated in two different ways, by thermal cyclic tests, basedon the TBCs behavior under cyclic thermal loads and by single-cylinder engine experiment. The characterization of the coatings was done by scanning electron microscope (SEM) before and after the thermal cyclic tests.The performance properties were correlated with coatings microstructure and thermophysical properties. It was shown that a columnar TBC produced by SPS had a superior engine efficiency in the single cylinder engine experiment.

In the present study, we sought to investigate the agreement between late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR) and electro-anatomical maps (EAM) of patients with non-ischemic dilated cardiomyopathy (NIDCM) and how it relates with the procedural outcome after catheter ablation of ventricular arrhythmias (VA). We identified 50 patients with NIDCM who underwent CMR and ablation for VA. LGE was detected in 16 patients (32%), mostly in those presenting with sustained VT (15 patients). Low-voltage areas (<1.5 mV) were observed in 23 patients (46%), in 7 patients (14%) without evidence of LGE. Using a threshold of 1.5 mV, a good and partially good agreement between the bipolar EAM and LGE-CMR was observed in only 4 (8%) and 9 (18%) patients, respectively. With further adjustments of EAM to match the LGE, we defined new cut-off limits of median 1.5 mV and 5 mV for bipolar and unipolar maps, respectively. Most VT exits were found in areas with LGE (12 out of 16 patients). VT exits were found in segments without LGE in 2 patients with unsuccessful ablation as well as in 2 patients with successful ablation, P=0.77. In patients with VT recurrence, the LGE volume was significantly larger than in those without recurrence: 12.2 ± 5.8% vs. 6.9 ± 3.4%; P=0.049. Myocardial heterogeneity provides the electrophysiological substrate of ventricular arrhythmias in patients with myocardial infarction. Fibrosis and reduction in the number of gap junctions of surviving myocytes allow the occurrence of re-entry (23). However, the relationship between fibrosis and VA is complex and involves not only fixed anatomical barriers but also functional blocks caused by differences in the fiber orientation, myocardial thickness mismatch or connexin downregulation (24-26). Studies involving EAM in patients with scar-related VT demonstrated that homogenization of the low-voltage areas with elimination of the signals showing abnormal amplitude and fractionation was associated with improved acute and long-term success rates (27). On the other hand, animal studies showed that CMR can be useful to characterize LV fibrosis. Moreover, the amount of LGE has been associated with inducibility of VT and is considered a powerful and independent predictor of adverse prognosis, especially in myocardial infarction patients (28-29). In contrast to ischemic cardiomyopathy, LGE is infrequently found in patients with NIDCM. A previous study of 399 patients with NIDCM demonstrated that LGE was detected in approximately one-fourth of the patients and was associated with a 9-fold increase of risk for SCD (30). In accordance with these data, we observed LGE in approximately one third of the patients, and most of them had a history of spontaneous sustained VT. In contrast to the VT patients who have frequently LGE, all patients with ventricular premature beats but without any sustained VT did not show any evidence of LGE in CMR. These observations support the general understanding that the presence of LGE identifies more advanced cardiomyopathy as well as a higher risk for more malignant ventricular arrhythmias. Although myocardial fibrosis is associated with a higher likelihood for VT occurrence, the absence of LGE in CMR does not completely eliminate the risk for VT. Some patients had sustained ventricular arrhythmias even without detectable scar in CMR, which suggests a poorer negative predictive value for the LGE. Although CMR imaging is currently considered the reference standard for the detection of LV scar, it has a limited spatial resolution in vivo. Therefore, minute scars as well as diffuse fibrosis that can still trigger VA may remain undetected. The alternative approach to detect myocardial scar is to characterize the electrical properties of the myocardium by using bipolar EAM in order to find low-voltage areas and late potentials that are markers of abnormal tissue. However, abnormal fragmentation and amplitudes below 1,5 mV are less frequently found in NIDCM in comparison to post-myocardial infarction patients. These findings illustrate the downsides of the EAM in NIDCM. Moreover, numerous animal and clinical studies underlined other technical drawbacks of the EAM that can influence the size and the characteristics of the low-voltage areas such as mapping electrode size and spacing, the angle of contact with the underlying tissue, wave-front direction (31-33). Recently, Betensky and al. analyzed the agreement between CMR and EAM in patients with NIDCM and found a significant discordance between both approaches in 36% of the patients. Using lower signal intensity threshold of 2 standard deviations they increased the CMR-EAM agreement up to almost 90% (34). In contrast to Betensky, who used a simplified approach analyzing only the septal to lateral disagreement, we choose to perform more precise analysis using the 17 segments AHA model of the LV. We found 23 out of 50 patients with low-voltage areas and 15 (71.4%) of them had sustained VT. Moreover only 16 (32%) patients with low-voltage had also LGE in the CMR. In our study the basal inferolateral, inferior and infero-septal segments were most frequently affected by LGE in contrast to the basal anterior and anteroseptal segments affected in the EAM. However, in the LGE positive patients, the best pace-mapping sites of the clinical VT coincided with areas of LGE. One possible explanation for the low correlation between EAM and LGE-CMR is the non-transmurality of the fibrosis in patients with NIDCM. A previous study in post-infarct patients demonstrated that median bipolar voltage <1.5 mV was only found in segments demonstrating ≥75% infarct transmurality (35). In a recently published article, Zeppenfeld et al. found that EAM voltages showed a linear relationship with the LV wall thickness and the amount of fibrosis in patients with non-ischemic DCM. However, no cutoff value for the voltage could be found to reliably delineate fibrotic areas in NIDCM (36). Regarding the quantification of the arrhythmogenic substrate, we could not find any correlation between the amount of LGE and the size of the low-voltage areas (endo- or epicardial), which can be explained by the impact of LGE transmurality as well as the sparse distribution of the LV fibrosis. In this regard, an advantage of the LGE-CMR is that it can visualize the presence of intramyocardial and epicardial scar which are not visible by endocardial EAM. The reason is that the bipolar EAM has narrower field of view and proved insensitive to delineate scar that lies deeper within the myocardium (37). Previously, Hutchinson et al. reported that by using a unipolar 8.27 mV threshold endocardial it was possible to identify epicardial bipolar low-voltage areas consistent with macroscopic scarring in patients with NIDCM and normal endocardial bipolar voltage (38). However, we found that the agreement between LGE and unipolar maps using this cutoff of 8.27 mV was poor. After adjusting the unipolar and bipolar threshold on the basis of CMR, the resulting median thresholds for the bipolar and unipolar low-voltage maps were 1.5 mV and 5 mV respectively, which are close to those observed in a previous study (37). 4.1 Conclusions LGE was observed in approximately one-third of the patients with dilated cardiomyopathy of non-ischemic origin and ventricular arrhythmias. LGE was seen mainly in patients with sustained VT. The agreement between the distribution or the extent of LGE and bipolar low-voltage areas was fairly poor. No particular cutoff values for bipolar and unipolar electro-anatomical maps could be found. On the other hand, most VT exits in patient with sustained VT were found in areas of LGE. The procedural success after VA ablation were related to LGE volume only.

OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

Bakgrund: Inom röntgenverksamhet används kontrastmedel som ett hjälpmedel för att påvisa skillnader mellan vävnader i kroppen. Gadoliniumbaserade kontrastmedel används till större delen vid MR undersökningar. Biverkningar anses ovanliga, men de förekommer och kan innebära allvarliga konsekvenser. Röntgensjuksköterskor behöver kunskap om dessa biverkningar för att kunna ge en patientsäker vård.  Syfte: Studien har således som syfte att undersöka biverkningar som kan uppstå vid administrering av gadoliniumkontrastmedel vid MRT undersökningar. Metod: En litteraturstudie med artikelsökningar i tre databaser PubMed, CinAhl samt Scopus. Tolv kvantitativa artiklar användes och bearbetades till att bilda kategorier och underkategorier genom innehållsanalys. Resultat: Utifrån artiklarna bildades kategorin Cirkulationssystem och luftvägar med underkategorier hjärtpåverkan och andningsproblem, kategorin Mag- tarmkanalen och bukorgan med underkategorier GI-systemet samt njurar, urinvägar och lever, kategorin Ändrade sinnesförnimmelser med underkategorier ögat, förnimmelser från smak och lukt, hudpåverkan och temperaturförnimmelser samt kategorin Påverkan av kommunicerbarhet och obehag med underkategorier medvetandepåverkan och obehagsupplevelse. Konklusion: De allvarligaste biverkningarna involverade hjärtpåverkan, andningsproblem, njurproblem samt medvetandepåverkan. De vanligaste biverkningarna förknippades med GI-systemet, Hudreaktioner och Obehagsupplevelser. Eftersom biverkningar var otroligt sällsynta vid administrering av Gadoliniumkontrastmedel finns det risk att vårdpersonal inte känner till biverkningarna och därmed inte är uppmärksamma.

The aim of this exploratory study was to evaluate the influence of hepatic steatosis on the detection rate of metastases in gadoxetic acid-enhanced liver magnetic resonance imaging (MRI). A total of 50 patients who underwent gadoxetic acid-enhanced MRI (unenhanced T1w in- and opposed-phase, T2w fat sat, unenhanced 3D-T1w fat sat and 3-phase dynamic contrast-enhanced (uDP), 3D-T1w fat sat hepatobiliary phase (HP)) were retrospectively included. Two blinded observers (O1/O2) independently assessed the images to determine the detection rate in uDP and HP. The hepatic signal fat fraction (HSFF) was determined as the relative signal intensity reduction in liver parenchyma from in- to opposed-phase images. A total of 451 liver metastases were detected (O1/O2, n = 447/411). O1/O2 detected 10.9%/9.3% of lesions exclusively in uDP and 20.2%/15.5% exclusively in HP. Lesions detected exclusively in uDP were significantly associated with a larger HSFF (area under curve (AUC) of receiver operating characteristic (ROC) analysis, 0.93; p < 0.001; cutoff, 41.5%). The exclusively HP-positive lesions were significantly associated with a smaller diameter (ROC-AUC, 0.82; p < 0.001; cutoff, 5 mm) and a smaller HSFF (ROC-AUC, 0.61; p < 0.001; cutoff, 13.3%). Gadoxetic acid imaging has the advantage of detecting small occult metastatic liver lesions in the HP. However, using non-optimized standard fat-saturated 3D-T1w protocols, severe steatosis (HSFF > 30%) is a potential pitfall for the detection of metastases in HP.

No description available.

L’imagerie par résonance magnétique (IRM) est couramment utilisée en médecine pour obtenir des images anatomiques de haute résolution. L’IRM permet également de suivre la migration de cellules injectées in vivo. Dans ce contexte, un agent de contraste est nécessaire afin de clairement visualiser les cellules. Actuellement, les produits de contraste les plus utilisés en IRM clinique sont les chélates de gadolinium puisqu’ils permettent de rehausser le signal des tissus fortement vascularisés. Cependant, la majorité de ces composés ne sont que faiblement internalisés et retenus à l’intérieur des cellules. Afin de permettre un marquage cellulaire plus efficace, des nanoparticules d’oxyde de gadolinium (Gd2O3) ont récemment été développées. La première partie de ce projet de maîtrise consistait donc en l’utilisation de ces particules, revêtues de diéthylène glycol (Gd2O3-DEG), comme marqueur cellulaire. Une fois marquées avec ce produit, les cellules peuvent être visualisées en IRM, in vitro et in vivo (œuf de poulet fertilisé). Or, les particules de Gd2O3-DEG s’agglomèrent en solution aqueuse saline (milieu de culture) et à haute concentration, elles peuvent affecter la prolifération des cellules. De ce fait, la seconde partie de ce projet consistait à remplacer le DEG par du polyéthylène glycol (PEG) afin de conférer aux nanocristaux une meilleure stabilité et de diminuer leur cytotoxicité. Dans le cadre de cette maîtrise, le greffage de PEG a été réalisé à l’aide de trois polymères différents, soit le PEG-phosphate, le PEG-silane et le PEG diacide. Dans le but de déterminer le meilleur groupement chimique pouvant réagir avec le Gd2O3, ces polymères ont été greffés à la fois sur les particules et sur des films minces de Gd2O3. Différentes stratégies de greffage ont été élaborées avec les deux systèmes afin d’identifier les conditions de réaction optimales. Suite à ces expériences, les caractéristiques physico-chimiques des particules et des surfaces recouvertes de PEG ont été mesurées à l’aide de différentes techniques d’analyse. En somme, cette étude a permis de démontrer que le PEG-phosphate interagit plus fortement avec les nanomatériaux à base de Gd2O3 que les deux autres PEG. De plus, les particules de Gd2O3-PEG-phosphate possèdent des propriétés physico-chimiques et relaxométriques supérieures à tous les autres systèmes étudiés dans le cadre de ce projet (nanoparticules revêtues de DEG, de PEG-silane et de PEG diacide). Ces particules pourraient donc être considérées, dans le futur, comme agent de contraste pour l’IRM cellulaire et pourraient remplacer les produits employés à ce jour (principalement des nanoparticules d’oxyde de fer). / Magnetic resonance imaging (MRI) is widely used in medicine to achieve high resolution, in-depth anatomical images. MRI can also be used to detect cells injected in vivo and to track their migration. For this purpose, the cells cannot be clearly visualized in MRI without the use of contrast agents. Gadolinium (III) complexes are by far the most widely used contrast agents in clinical medicine because they provide a drastic enhancement of MRI signal in vascularized tissues. However, the vast majority of these chelates is poorly uptaken and retained into cells. In order to efficiently label cells, gadolinium oxide nanoparticles (Gd2O3) have been recently developed. Therefore, these particles, covered with diethylene glycol (DEG-Gd2O3), were used in the first part of this project to label cells. DEG-Gd2O3-labeled cells can be visualized in MRI, in vitro and in vivo (using the chicken embryo model). However, DEG-Gd2O3 particles aggregate in aqueous saline solution (cell culture medium) and at high concentration, they can impact on the cell proliferation. Molecules such as polyethylene glycol (PEG) can be used to remove DEG so as to improve the stability of the particles and to limit their cytotoxicity. In the course of this project, DEG-Gd2O3 particles were treated with three different polymers: PEG-phosphate, PEG-silane and PEG diacid. In order to determine the functional group that can react strongly with the rare-earth oxide, these polymers were grafted on both Gd2O3 particles and thin films. Different grafting methodologies were developed to identify the optimal reaction conditions. The physicochemical properties of the PEG-Gd2O3 particles and the PEG-treated surfaces were measured with different surface characterization techniques. In conclusion, this study shows that PEG-phosphate reacts more strongly with Gd2O3 nanomaterials compared to the other PEG derivatives. Moreover, PEG-phosphate-Gd2O3 particles have better physicochemical and relaxometric properties than all the other systems studied in this research project (particles covered with DEG, PEG-silane and PEG diacid). These particles might be considered in the future as a potential contrast agent for cellular MRI and could replace the products used currently (mainly iron oxides nanoparticles).

Metal-insulator-metal (MIM) capacitors are used for analog, RF, and DRAM applications in ICs. The International Technology Roadmap for Semiconductors (ITRS) specifies continuing increase in capacitance density (> 7 fF/ m2), lower leakage current density (< 10 8 A/cm2), very low effective oxide thickness (EOT < 1 nm, for DRAM applications), and better capacitance density-voltage (C-V) linearity ( < 100 ppm/V2, for analog/RF applications). In addition, the maximum fabrication/processing temper-ature should not be greater than 400 0C, in order to be compatible with the thermal budget of back-end fabrication steps. Low dielectric constants of conventional SiO2 and Si3N4 capacitors limit the capacitance densities of these devices. Although scaling down of dielectric thickness increases the capacitance density, it results in large leakage current density and poor C-V linearity. In this work, the effects of high-k materials (Eu2O3, Gd2O3, TiO2) on the device performance of MIM capacitors are studied. The performance of multi-dielectric stack, and doped-dielectric stack devices are also investigated. The effects of anneal temperature, anneal ambient, anneal mode, and dielectric thickness on device performance are evaluated. C-V, current density-voltage (J-V), and reliability measurements are performed to benchmark the electrical performance, and this is correlated to the structural and material properties of the films through ellipsometry, scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) measurements. High-performance MIM capacitors are fabricated by using (RF sputtered) Eu2O3 dielectric. The fabricated devices are subjected to different anneal conditions, to study their device performance. Forming gas (FG) and argon (Ar) annealed devices are shown to have higher capacitance densities (7 fF/ m2jF G), lower leakage current densities (3.2 10 8 A/cm2jAr at -1 V), and higher , compared to oxygen (O2) annealed de-vices ( 100kHz = 193 ppm/V2jO2). The electrical characterization results are correlated with the surface chemical states of the films through XPS measurements. The annealing ambient is shown to alter the surface chemical states, which, in turn, modulate the electrical characteristics. High-density MIM capacitors are fabricated by using (RF sputtered) Gd2O3, and Gd2O3-Eu2O3 stacked dielectrics. The fabricated Gd2O3 capacitors are also subjected to different anneal conditions, to study their device performance. Although Gd2O3 capacitors provide high capacitance density (15 fF/ m2), they suffer from high leakage current density, high , and poor reliability. Therefore, stacked dielectrics of Gd2O3 and Eu2O3 (Gd2O3/Eu2O3 and Eu2O3/Gd2O3) are fabricated to reduce leakage current density, improve , and improve reliability, with only a marginal reduction in capacitance density, compared to Gd2O3 capacitors. Density of defects and barrier/trap heights are extracted for the fabricated capacitors, and correlated with the device characteristics. High-performance MIM capacitors with bilayer dielectric stacks of (ALD-deposited) TiO2-ZrO2, and Si-doped ZrO2 are characterized. Devices with (ALD-deposited) TiO2/ ZrO2/TiO2 (TZT) and AlO-doped TZT stacks are also characterized. The influence of doping on the device performance is studied. The surface chemical states of the deposited films are analyzed by high-resolution XPS. The structural analysis of the samples is performed by XRD measurements, and this is correlated to the electrical characteristics of the devices. Reliability measurements are performed to study the effects of constant voltage and current stress on device performance. High capacitance density (> 45 fF/ m2), low leakage current density (< 5 10 8 A/cm2 at -1 V, for most devices), and sub-nm EOT are achieved. These parameters exceed the ITRS specifications for DRAM storage capacitors.

No description available.