<p>Whereas the effect of size and coating material on the pharmacokinetics and biodistribution of iron oxide based contrast agents are well documented, the effect of these parameters on liver metabolism has never been investigated. The primary purpose of this work was to evaluate the effect of iron oxide particle size and coating on the rate of liver clearance and particle degradation using a rat model. </p><p>The magnetic and relaxation properties of five different iron oxide contrast agents were determined prior to the onset of the animal studies. The R2* values and the T1-enhancing efficacy of the agents were also evaluated in blood using phantom models. The results of these studies indicated that the efficacy of these agents was matrix and frequency dependent. Correlations between the R2* values and the magnetic properties of the agents were established and a new parameter, Msat/r1, was created to enable better estimations of contrast agent T1-enhancing efficacy in blood. </p><p>The bio-distribution of one of the agents was also evaluated to assess the importance of sub-cellular particle distribution, using an isolated rat liver cell model. Phantom models were also used to verify that materials with magnetic properties similar to the particle breakdown products (ferritin/hemosiderin) may induce signal reduction when compartmentalized in a liver cell suspension. The results revealed that the cellular distribution of the agent did not influence the rate of particle degradation. This finding conflicted with current theory. Additionally, the study indicated that the compartmentalization of magnetic materials similar to ferritin may induce significant signal loss.</p><p>Methods enabling the accurate determination of contrast agent concentration in the liver were developed and validated using one of the agents. From these measurements the liver half-life of the agent was estimated and compared to the rate of liver clearance, as determined from the evolution of the effective transverse relaxation rate (R2*) in rat liver. The results indicate that the liver R2* enhancement persisted at time points when the concentration of contrast agent present in the liver was below method detection limits. The prolonged R2* enhancement was believed to be a result of the compartmentalisation of the particle breakdown products within the liver cells. </p><p>Finally, the liver clearance and degradation rates of the five different iron oxide particles in rat liver were evaluated. The results revealed that for materials with similar iron oxide cores and particle sizes, the rate of liver clearance was affected by the coating material present. Materials with similar coating, but different sizes, exhibited similar rates of liver clearance.</p><p>In conclusion, the results of this work strongly suggest that coating material of the iron oxide particles may contribute significantly to the rate of iron oxide particle clearance and degradation in rat liver cells.</p>

Whereas the effect of size and coating material on the pharmacokinetics and biodistribution of iron oxide based contrast agents are well documented, the effect of these parameters on liver metabolism has never been investigated. The primary purpose of this work was to evaluate the effect of iron oxide particle size and coating on the rate of liver clearance and particle degradation using a rat model. The magnetic and relaxation properties of five different iron oxide contrast agents were determined prior to the onset of the animal studies. The R2* values and the T1-enhancing efficacy of the agents were also evaluated in blood using phantom models. The results of these studies indicated that the efficacy of these agents was matrix and frequency dependent. Correlations between the R2* values and the magnetic properties of the agents were established and a new parameter, Msat/r1, was created to enable better estimations of contrast agent T1-enhancing efficacy in blood. The bio-distribution of one of the agents was also evaluated to assess the importance of sub-cellular particle distribution, using an isolated rat liver cell model. Phantom models were also used to verify that materials with magnetic properties similar to the particle breakdown products (ferritin/hemosiderin) may induce signal reduction when compartmentalized in a liver cell suspension. The results revealed that the cellular distribution of the agent did not influence the rate of particle degradation. This finding conflicted with current theory. Additionally, the study indicated that the compartmentalization of magnetic materials similar to ferritin may induce significant signal loss. Methods enabling the accurate determination of contrast agent concentration in the liver were developed and validated using one of the agents. From these measurements the liver half-life of the agent was estimated and compared to the rate of liver clearance, as determined from the evolution of the effective transverse relaxation rate (R2*) in rat liver. The results indicate that the liver R2* enhancement persisted at time points when the concentration of contrast agent present in the liver was below method detection limits. The prolonged R2* enhancement was believed to be a result of the compartmentalisation of the particle breakdown products within the liver cells. Finally, the liver clearance and degradation rates of the five different iron oxide particles in rat liver were evaluated. The results revealed that for materials with similar iron oxide cores and particle sizes, the rate of liver clearance was affected by the coating material present. Materials with similar coating, but different sizes, exhibited similar rates of liver clearance. In conclusion, the results of this work strongly suggest that coating material of the iron oxide particles may contribute significantly to the rate of iron oxide particle clearance and degradation in rat liver cells.

Contrast agents are of great importance in clinical applications of Magnetic Resonance Imaging (MRI) to improve the contrast of internal body structures and to obtain tissue-specific image. However, current approved contrast agents still have limitations including low relaxivity, low specificity and uncontrolled blood circulation time, which motivated researchers to develop novel contrast agents with higher relaxivity, improved targeting abilities and optimal retention time. This thesis uses animal experimental data from Dr. Jenny J. Yang’s lab at the Department of Chemistry in Georgia State University to study effects of a class of newly designed protein-based MRI contrast agents (ProCAs). Models for the longitudinal data on MRI intensity are constructed to evaluate the efficiency of different MRI contrast agents. Statistically significant results suggest that ProCA1B14 has the great potential to be a tumor specific contrast agent and ProCA32 could be a promising MRI contrast agent for the liver imaging in clinical applications.

Le traitement des gliomes de haut grade représente un réel défi médical. Les techniques de thérapies actuelles sont principalement à visée palliative et leur efficacité est limitée. De nombreuses stratégies thérapeutiques sont explorées pour trouver un traitement curatif. La radiothérapie stéréotaxique par rayonnement synchrotron (SSRT) est une technique innovante dont le principe repose sur l'accumulation sélective d'un élément lourd (Z élevé) dans la tumeur, suivie d'une irradiation stéréotaxique avec un faisceau monochromatique de rayons X, de faible énergie (50-100 keV), issus d'une source synchrotron. Une augmentation de la dose déposée localement dans la tumeur est obtenue grâce au renforcement de l’effet photoélectrique dans ces conditions. Cette thèse s’inscrit dans le cadre des essais cliniques de phase I et II de la SSRT menés sur des métastases cérébrales, au synchrotron européen à Grenoble. Une injection systémique d’un agent de contraste iodé et un faisceau synchrotron de 80 keV sont utilisés lors de ces essais. L’efficacité de la SSRT repose directement sur la concentration de l’agent de contraste iodé accumulé dans la tumeur, sa stabilité au cours du temps et sa reproductibilité chez le même patient. L’objectif principal de ce travail a été d’évaluer et de modéliser les concentrations d'iode moyennes atteintes dans des métastases cérébrales, d’une part, et d’appréhender les impacts dosimétriques, engendrés par les variations spatiales et temporelles de ces concentrations sur le traitement des patients, d’autre part. Un protocole d'imagerie scanner a été conçu spécifiquement pour cette étude afin de permettre le suivi, temporel et spatial, des concentrations d'iode et l’extraction des paramètres de perfusion cérébrale dans une métastase cérébrale. Une méthodologie d'analyse expérimentale et une modélisation théorique de la bio-distribution d'iode dans des métastases cérébrales ont été développées. Un modèle mathématique reliant les concentrations d'iode aux paramètres de perfusion a été établi, dans le but de prédire les concentrations d'iode chez chaque patient et de réduire la durée du protocole de suivi. La reproductibilité de la prise de contraste a été caractérisée chez des patients à dix jours d’intervalle. Les impacts dosimétriques des écarts de concentrations d'iode observés sur les plans de traitement en SSRT ont été analysés. Ces derniers ont été comparés aux plans de traitement obtenus avec différentes techniques de pointe en radiothérapie afin d’évaluer les performances dosimétriques de la SSRT. / Gliomas treatment is still a challenging disease in medicine. Available treatments are mainly palliative and their efficiency is limited. Since years, many therapeutic strategies have been explored to find a cure. Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumours with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. A localised dose enhancement in brain tumours is obtained due to the reinforced photoelectric absorption in these conditions. This thesis takes part in the framework of phase I/II clinical trials, which are underway at the European Synchrotron Radiation Facility in Grenoble, France. These trials are realised on human brain metastasis using venous infusion of iodinated contrast agents and a 80 keV X-ray beam. The radiation dose enhancement depends on the amount of iodine in the tumour, its time course and its reproducibility for each patient. The aim of this work was to evaluate and model the amounts of iodine concentrations reached in brain metastasis, and to analyse the dosimetric deviations caused by spatial and temporal variations of these concentrations during the treatments. A CT cine scan protocol was designed especially for this study in order to extract quantitative iodine concentrations and associated brain perfusion parameters in human brain metastasis, as key parameters for treatment feasibility and quality. An experimental analysis methodology and a theoretical model of iodine biodistribution were developed. A mathematical relationship between iodine concentrations and perfusion parameters was established in order to estimate these concentrations for each patient in the future and to reduce the imaging dose, associated to the prolonged imaging acquisition time. The reproducibility of iodine uptake between the CT planning scan day and the treatment day was assessed (~10 days interval). The impact of iodine concentration variations on reference SSRT dosimetries was analysed. Finally, SSRT treatment plans were compared to those obtained with different cutting-edge radiotherapy techniques in order to evaluate dosimetric performances of SSRT.

Made available in DSpace on 2014-06-11T19:22:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-03Bitstream added on 2014-06-13T19:49:15Z : No. of bitstreams: 1 paula_as_me_sjrp.pdf: 3130641 bytes, checksum: 88335016faa035282519ac1dcb6b41b9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Como em qualquer método de imagem utilizado em medicina, foi desenvolvido para a ressonância magnética por imagem (MRI) um agente de contraste que pudesse realçar apenas as lesões e não os tecidos normais, possibilitando desta maneira não apenas a localização do tecido afetado, mas propiciando também um diagnóstico mais preciso e diferenciado. Os agentes de contraste geralmente utilizados em MRI afetam seletivamente os tempos de relaxamento T1 dos diferentes tecidos, embora os tempos de T2 podem também ser alterados pela introdução desses agentes. Este trabalho caracteriza-se pela busca de novos compostos micro ou mesoporosos que possam ser utilizados como agentes de contraste para MRI. A principal diferença entre os compostos estudados e os quelatos de gadolínio empregados atualmente em MRI está na usa composição química e estado físico. Estes novos compostos são zeólitos, cuja principal característica é sua estrutura altamente cristalina formada por canais e cavidades bem definidas, canais e cavidades onde ocorre a imobilização de íons metálicos. As sínteses destes novos materiais microporosos foram realizadas utilizando-se templates orgânicos derivados da decahidroquinolina, 2,6 dimetil piperidina, 3,5 dimetil piperidina e espartênio. Antes de serem utilizados em diferentes condições de química sol-gel os novos templates sintetizados foram caracterizados por ressonância magnética nuclear ( 13 C e 1 H), espectrometria de massa e por difração de raios-X de monocristais. Os novos materiais microporosos foram sintetizados em diferentes condições de química sol- gel e os principais produtos obtidos foram novos vanadiosilicatos. Os novos materiais microporosos foram caracterizados pelas técnicas de difração de raios-X, ressonância magnética do estado sólido dos núcleos 29 Si, 51 V e 13 C, microscopia eletrônica de varredura, espalhamento Raman... / As in any other imaging method used in modern medicine, Magnetic Resonance Imaging (MRI) requires a contrast media. The contrast media can enhance the contrast of the damage tissue in comparison to the normal ones, facilitating the location of the damage area and providing information for a precise diagnosis. Most of the contrast media commonly used in MRI, affect the relaxation time T1 of the different tissues, and in some case also the relaxation time T2. The main goal of this work was the searching for new microporous or mesoporous materials that could replace the traditional contrast media based on chelates of gadolinium. These microporous materials, different form the chelates of gadolinium, are made up by well defined system of nanoporous and nanochanels where the metal are located. In order to synthesized these new microporous materials, a new family of structure directing agents (SDAs) derivatives of decahydroquinolinium; 2,6 dimethyl piperidine; 3,5 dimethyl piperidine and (S)-Sparteinium were synthesized. The as made new templates were fully characterized by 13 C, 1 H-NMR, ES- Mass Spectrometry, and single crystal X-Ray diffraction. Different sol gel chemistry conditions were studied and explored throughout this study using the new SDAs, however the most out sanding results were obtained for vanadosilicates. The new vanadosilicates were fully characterized by 13 C, 29 Si and 51 V NMR-MAS (Nuclear Magnetic Resonance-Magic Angle Spinning), Scanning electronic microscopy (SEM), Raman scattering and Thermogravimetric analysis (TGA). Some of the vanadosilicates synthesized with SDAs (1, 2, 3, 5, 7, 8, 9, 10, 11) were found to be isomorphous to the Titanosilicate ETS-10 and to the Vanadosilicate AM-6, which open up the possibility of their use as catalyst for shape selectivity oxidative calalysis. Althoug, Vanadosilicates prepared with N-Etil-Sparteinium are stil under... (Complete abstract click electronic access below)

De très nombreuses pathologies cérébrales s’accompagnent de phénomènes inflammatoires soit primitifs comme dans la sclérose en plaques (SEP), soit secondaires comme après un infarctus cérébral ou un traumatisme crânien. Dans tous les cas on observe la présence d’œdème vasogénique et de cellules inflammatoires.Dans une première approche chez l’animal, nous avons étudié la régulation et le rôle de la protéine canal aquaporine 4 (AQP4) dans l’œdème associé à l’inflammation et dans la sévérité de l’inflammation elle-même. Nous avons, de plus, validé un modèle de lésion inflammatoire focale type SEP pour étudier l’œdème et l’inflammation en fonction du microenvironnement, soit dans la substance blanche (SB), soit dans la substance grise (SG). Dans une seconde approche translationnelle chez les patients SEP, nous avons combiné un marqueur IRM d’altération de la barrière hémato-encéphalique (gadolinium) avec un marqueur plus spécifique de la composante cellulaire (USPIO) pour détecter les lésions « actives » et déterminer leur pronostic.Nous avons d’abord montré qu’AQP4 était surexprimée en situation d’œdème vasogénique associé à l’inflammation. Plus précisément, la surexpression d’AQP4 était plus marquée lors de la phase de résorption que lors de la phase de formation de l‘œdème. De plus, le fait d’inhiber AQP4 aggravait la sévérité de l’œdème et de l’inflammation dans la SB et dans la SG. Nous avons conclu au rôle protecteur d’AQP4 en situation d’inflammation en accord avec les données sur l’implication d’AQP4 dans la résorption de l’œdème et la mise en place de la cicatrice gliale. La surexpression d’AQP4, en tant que mécanisme protecteur, semblait insuffisante pour contrer la phase initiale de l’inflammation car elle ne devenait importante que secondairement. Deuxièmement, lorsque l’on induisait la même attaque inflammatoire dans la SB et dans la SG (modèle focal de SEP), les différences de microenvironnement ne permettaient pas d’induire de différence en termes de sévérité de l’œdème et de l’inflammation. Cette observation suggère de rechercher des différences de physiopathologie entre les lésions de la SB et celles de la SG pour expliquer le caractère faiblement inflammatoire et œdémateux des lésions de la SG chez les patients SEP. Pour finir, nous avons montré que l’observation de la composante cellulaire de l’inflammation in vivo grâce aux USPIO augmentait la sensibilité pour la détection des lésions actives de SEP. Les USPIO montraient également la faible inflammation résiduelle dans les formes chroniques de SEP. L’association des USPIO et du gadolinium augmentait également la spécificité en identifiant un sous-groupe de lésions se rehaussant avec les deux agents et apparaissant plus sévère.Nous avons apporté des connaissances nouvelles sur la physiopathologie de l’œdème et de la composante cellulaire de l’inflammation. Si nos résultats se confirment chez l’homme, l’AQP4 pourrait devenir une nouvelle cible thérapeutique. La meilleure compréhension des différences entre les lésions de la SB et de la SG dans la SEP est également une étape importante pour des thérapeutiques plus ciblées. Un bio-marqueur utilisable in vivo reflétant la composante cellulaire de l’inflammation (USPIO) améliore la sensibilité et la spécificité et pourrait aider à évaluer les nouvelles thérapeutiques. / Inflammation is a contributing factor in many diseases of the brain, including primary inflammatory disorders such as multiple sclerosis (MS) and secondary inflammation following stroke, brain trauma or even tumors. Vasogenic edema and white blood cell infiltration are common features of all inflammatory reaction subtypes. We first performed experimental studies in rodent animal models to better understand the regulation and role of the water channel protein aquaporin 4 (AQP4) in edema associated with inflammation and in the severity of the inflammation itself. We further validated a focal animal model of MS-like lesions to explore whether inflammation and edema differed according to the microenvironment either in gray matter (GM) or white matter (WM). In a second approach in MS patients, we combined a MR marker of blood brain barrier alteration (gadolinium) with a more specific marker of the cellular component of inflammation (USPIO) to detect active lesions and address their prognosis.First, we found that AQP4 was upregulated under conditions associated with vasogenic edema such as inflammation. Specifically, AQP4 upregulation was more important in the edema resolution phase than in the edema build-up phase. Furthermore, silencing AQP4 aggravated the severity of edema and inflammation in both WM and GM. We concluded that AQP4 has a protective role under inflammatory conditions, in agreement with the previously demonstrated role of AQP4 in edema resolution and glial scar formation. AQP4 upregulation, a potential protective mechanism, seems insufficient to counter the initial phase of inflammation because it reached a maximum only after a delay. Second, the severity of the edema and inflammation in WM and GM was not significantly different according to the microenvironment (either WM or GM) upon induction by the same inflammatory attack. This suggests that the pathogenesis in WM and GM is different and should be further explored to explain why little inflammation and edema is encountered in GM lesions of MS patients. Finally, we found that tracking the cellular macrophage component of inflammation with USPIO increased the sensitivity to active lesions in MS patients. It could even detect mild residual inflammation in patients with a progressive MS. Combining USPIO and gadolinium also increased the specificity; the subgroup of lesions that were enhanced with both contrast agents had more severe features. We have provided a better understanding of edema and the cellular component of inflammation. If confirmed in humans, AQP4 could be a new target for medication of edema. A better understanding of the WM/GM difference in MS is also a first step in developing more specific therapeutic strategies. Finally, the in vivo marker of the cellular component of inflammation (USPIO) provides more sensitive and specific information that could be useful in monitoring the efficacy of treatments.

The natural dynamics are not ideal or linear. To understand their complex behavior, we needs to study the nonlinear dynamics in more simple models. This thesis is consist of two main setups. Both setups are simplified models for the behavior occurs in the complex systems. We studied in both systems the same nonlinear dynamics such as higher-harmonics, sub-harmonics, solitary waves,...etc. In Chapter (2), the propagation of nonlinear waves in a lattice of repelling particles is studied theoretically and experimentally. A simple experimental setup is proposed, consisting in an array of coupled magnetic dipoles. By driving harmonically the lattice at one boundary, we excite propagating waves and demonstrate different regimes of mode conversion into higher harmonics, strongly in influenced by dispersion. The phenomenon of acoustic dilatation of the chain is also predicted and discussed. The results are compared with the theoretical predictions of FPU equation, describing a chain of masses connected by nonlinear quadratic springs. The results can be extrapolated to other systems described by this equation. We studied theoretically and experimentally the generation and propagation of kinks in the system. We excite pulses at one boundary of the system and demonstrate the existence of kinks, whose properties are in very good agreement with the theoretical predictions, that is the equation that approaches, under the conditions of our experiments, the one corresponding to full model describing a chain of masses connected by magnetic forces. The results can be extrapolated to other systems described by this equation. Also, In the case of a lattice of finite length, where standing waves are formed, we report the observation of subharmonics of the driving wave. In chapter (3), we studied the propagation of intense acoustic waves in a multilayer crystal. The medium consists in a structured fluid, formed by a periodic array of fluid layerswith alternating linear acoustic properties and quadratic nonlinearity coefficient. We presents the results for different mathematicalmodels (NonlinearWave Equation,Westervelt Equation and Constitutive equations). We show that the interplay between strong dispersion and nonlinearity leads to new scenarios of wave propagation. The classical waveform distortion process typical of intense acoustic waves in homogeneous media can be strongly altered when nonlinearly generated harmonics lie inside or close to band gaps. This allows the possibility of engineer a medium in order to get a particular waveform. Examples of this include the design of media with effective (e.g. cubic) nonlinearities, or extremely linear media. In chapter (4), the oscillatory behavior of a microbubble is investigated through an acousto-mechanical analogy based on a ring-shaped chain of coupled pendula. Observation of parametric vibration modes of the pendula ring excited at frequencies between 1 and 5 Hz is considered. Simulations have been carried out and show spatial mode, mixing and localization phenomena. The relevance of the analogy between a microbubble and the macroscopic acousto-mechanical setup is discussed and suggested as an alternative way to investigate the complexity of microbubble dynamics. / La dinámica natural no es ideal ni lineal. Para entender su comportamiento complejo, necesitamos estudiar la dinámica no lineal en modelos más simples. Esta tesis consta de dos configuraciones principales. Ambas configuraciones son modelos simplificados de el comportamiento que se produce en los sistemas complejos. Estudiamos en ambos sistemas la misma dinámica no lineal como son la generación de armónicos superiores, los sub-armónicos, las ondas solitarias, etc. En elCapítulo (2), se estudia, tanto teórica comoexperimentalmente, la propagación de ondas no lineales en sistemas periodicos de partículas acopladas mediante fuerzas repulsivas. Se propone una configuración experimental simple, que consiste en una matriz de dipolos magnéticos acoplados. Inyectando armónicamente la señal en un extremo, excitamos ondas de propagación y demostramos diferentes regímenes de conversión de modos en armónicos, fuertemente influenciados por la dispersión. También se predice y se discute el fenómeno de dilatación acústica de la cadena. Los resultados se comparan con las predicciones teóricas de la ecuación FPU, describiendo una cadena de masas conectadas por muelles cuadráticos no lineales. Los resultados pueden ser extrapolados a otros sistemas descritos por esta ecuación. Estudiamos también teórica y experimentalmente la generación y propagación de kinks. Excitamos pulsos en la frontera del sistema y demostramos la existencia de kinks cuyas propiedades están en muy buen acuerdo con las predicciones teóricas, es decir, con la ecuación que aproxima bajo las condiciones de nuestros experimentos la correspondiente al modelo completo que describe un cadena de masas conectadas por fuerzas magnéticas. Los resultados pueden ser extrapolados a otros sistemas descritos por esta ecuación. Además, en el caso de una red finita, donde se forman ondas estacionarias, describimos la observación de subarmónicos del armónico principal. En el capítulo (3), estudiamos la propagación de ondas acústicas intensas en un cristal multicapa. El medio consiste en un fluido estructurado, formado por un conjunto periódico de capas fluidas con propiedades acústicas lineales alternas y coeficiente de no linealidad cuadrática. Presentamos los resultados de diferentes modelos matemáticos (ecuación de ondas no lineal, ecuación de Westervelt y ecuaciones constitutivas). Mostramos que la interacción entre la fuerte dispersión y la no linealidad conduce a nuevos escenarios de propagaciónde ondas. El proceso de distorsión de la onda clásica, típico de las ondas acústicas intensas en medios homogéneos, puede ser alterado de forma importante cuando los armónicos generados no linealmente se encuentran dentro o cerca del gap. Esto permite la posibilidad de diseñar un medio con el fin de obtener una forma de onda en particular. Ejemplos de esto incluyen el diseño demedios con no linealidad efectiva (por ejemplo, cúbica) o medios extremadamente lineales. En el capítulo (4), el comportamiento oscilatorio de una microburbuja se investiga a través de una analogía acusto-mecánica basada en una cadena en forma de anillo de péndulos acoplados. Se estudian los modos de vibración paramétrica del anillo pendular excitado a frecuencias entre 1 y 5 Hz. Se han llevado a cabo simulaciones que muestran la presencia de modos espaciales, mixtos y fenómenos de localización. Se discute la relevancia de la analogía entre una microburbuja y la configuración macroscópica acústico-mecánica y se sugiere como una vía alternativa para investigar la complejidad de la dinàmica de microburbujas. / La dinàmica natural no és ideal ni tampoc lineal. Per entendre el seu comportament complex, es necessita estudiar la dinàmica no lineal dels models més simples. Aquesta tesi consisteix en l'estudi de dues configuracions principals, que són models simplificats del comportament que es produeix en els sistemes complexos. Estudiem en ambdós sistemes la mateixa dinàmica no lineal, com és la generació d'harmònics superiors, sub-harmònics, ones solitàries, etc. En el capítol (2), estudiem, tant teòrica com experimentalment, la propagació de les ones no lineals en sistemes periòdics de partícules acoblades mitjançant forces repulsives. Es proposa una configuració experimental simple, que consisteixen en una matriu de dipols magnètics acoblats. En conduint harmònicament la xarxa en un límit, excitemla propagació de les ones i demostrem diferents règims de conversió de modes en harmònics més alts, força influenciada per la dispersió. El fenomen de la dilatació acústica de la cadena també es prediu i es discuteix. Els resultats es comparen amb les prediccions teòriques que descriu una cadena de masses conectades per molls quadràtics no lineals. Els resultats es poden extrapolar a altres sistemes descrits per aquesta equació. Hem estudiat teòrica i experimentalment la generació i propagació de Kinks. Excitem polsos a la frontera del sistema i demostrem l'existència d'Kinks, les propietats desl quals estan en molt bon acord amb les prediccions teòriques, és a dir, de l'equació que aproxima sota les condicions dels nostres experiments la corresponent al model complet que descriu un cadena demasses connectades per forcesmagnètiques. Els resultats es poden extrapolar a altres sistemes descrits per aquesta equació. A més, en el cas d'una xarxa finita, on es formen ones estacionàries, descrivim l'observació de subarmónicos de l'harmònic principal. En el capítol (3), s'estudia la propagació d'ones acústiques intenses en un medi multicapa. El medi consisteix en un fluid estructurat, format per una matriu periòdica de capes de fluid amb l'alternança de propietats acústiques lineals i coeficient de no linealitat de segon grau. Es presenten els resultats per a diferents models matemàtics no lineals (equació d'ones no lineal, equació de Westervelt i les equacions constitutives). Es demostra que la interacciò entre la forta dispersió i no linealitat condueix a nous escenaris de propagació de l'ona. El procés de distorsió en formad'ona clàssica, típica de les ones acústiques intenses en medis homogenis, es pot alterar de manera significativa quan els harmònics generats de forma no lineal es troben dins o a prop del gap. Això obri la possibilitat de dissenyar unmedi per tal d'obtenir una forma d'ona particular. Exemples d'això inclouen el disseny delsmedis amb una no linealitat efectiva (per exemple cúbica), o medis extremadament lineals. En el capítol (4), el comportament oscilatori d'una micro-bombolla és investigat a través d' una analogia acústica-mecànica basada en una cadena en forma d'anell de pèndols acoblats. Es considera l'observació dels modes de vibració paramètriques de l'anell pendular excitat amb freqüències entre 1 i 5 Hz. S'han dut a terme simulacions que mostren la presència de moes espacilas, mixtes i fenòmens de localització. Es discuteix la relevància de l'analogia entre les microbambolles i la configuració macroscòpica acústica-mecànica i es suggereix una formaalternativa per a investigar la complexitat de la dinàmica demicrobombolles. / Mehrem Issa Mohamed Mehrem, A. (2017). Nonlinear acoustics in periodic media: from fundamental effects to applications [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/80289 / TESIS

This thesis deals mainly with perfusion modeling in optical coherence tomography (OCT). The introductory part deals with basic theory of the OCT, including a description of its basic applications. Part of the work was the testing of selected contrasting materials suitable for the OCT and the design and implementation of phantoms, which were subsequently used in the main part of the thesis. In the practical part, attention is paid to the perfusion analysis in the OCT, first the application of the dilution theory in the OCT for flow estimation, then a study testing the basic theory of perfusion on OCT by means of tissue phantom. Another part of the thesis is devoted to the method of speckle variance analysis for flow visualization.

This work deals with preparation of microbubble suspension from a mixture of phospholipids, palmitic acid and polyethylene glycol. Properties of prepared systems were studied using bubble tensiometry and dynamic light scattering method and were compared with commercial contrast agent SonoVue®. Suspensions were prepared in various conditions including different atmosphere and increased temperature in some steps of preparation and different solution. Effect of polyethylene glycol addition on surface activity of the system was studied. Surface activity of phospholipids was insignificant. Surface tension decreased with increasing concentration and molecular weight of polyethylene glycol in the system. Effect of different atmosphere and increased temperature showed no substantial trend. It emerged that dynamic light scattering is not suitable for this type of samples because of high polydispersity and phase separation of the system.

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.