Ce travail de thèse a pour but l’étude de l’influence du nanoconfinement sur le comportement du radical phénoxyle. Une nouvelle méthodologie de génération des radicaux phénoxyle à l’état solide a été mise au point. Elle fait intervenir la fragmentation de motifs diazène et ne nécessite ni solvant ni co-réactif. Une étude de spin-trapping a permis de valider cette approche. Ainsi a été synthétisée une grande variété de matériaux hybrides organique-inorganiques, de type silice mésoporeuse (SBA 15, MCM-41) et de type polysilsesquioxane lamellaire ou poreux, fonctionnalisés par différents précurseurs de radicaux phénoxyle. Les propriétés spectroscopiques du radical phénoxyle confiné dans ces matériaux ont été étudiées par RPE en onde continue ou pulsée. Ces matériaux permettent d’augmenter de manière remarquable la durée de vie des radicaux phénoxyle. Dans ces conditions, ces derniers peuvent être qualifiés de persistants et dans certains cas de stables. L’influence du confinement a également pu être mis en évidence sur les propriétés de relaxation du radical. Enfin, une application de ces matériaux en tant que photo-initiateurs de polymérisation radicalaire a été développée. / Abstract : The aim of this study is to explore the influence of nanoconfinement on the phenoxyl radical behavior. A new methodology allowing the traceless solid state generation of phenoxyl radical was developed. It relies on the fragmentation of a diazene moieties and no solvent nor co-reagent are needed. A spin-trapping study was used to validate this approach. A wide variety of organic-inorganic hybrid materials, like mesoporous silica (SBA-15, MCM-41) and lamellar or porous polysilsesquioxane, functionalized with various phenoxyl radical precursors was synthesized. The spectroscopic properties of the phenoxyl radical contained in these materials were studied by EPR. These materials enable an amazing increase of the phenoxyl radical lifetime, they transform transient phenoxyl radical into persistent and even stable ones. The influence of the confinement has also been observed on the radical relaxation properties. Finally, an application of these materials as polymerization photo-initiator was successfully developed.

Abstract Osteoarthritis (OA) is a common chronic condition that reduces the quality of life of millions of individuals worldwilde. In OA, the progressive degradation of articular cartilage (AC) and bone can cause joint pain and disability. Currently there is no effective treatment available for OA besides gross joint replacement surgery. This is largely due to the lack of accurate biomarkers to test potential drugs and treatments that could stop or reverse the disease progression. The primary tools in use for OA diagnostics are inadequate in the early stage of the disease and merely allow its late manifestations to be visualized. Quantitative MRI (qMRI) has demonstrated the ability to distinguish degenerated from intact AC prior to radiographic changes. Moreover, so-colled rotating frame relaxation time parameters are sensitive to the slow molecular motion domain, relevant for clinical applications. T1ρ and T2ρ relaxation time measurements using adiabatic spin-lock pulses (AdT1ρ and AdT2ρ) have shown superior sensitivity to cartilage degeneration in vitro over conventional qMRI parameters. This thesis aimed to compare the differences that exist between established qMRI methods for AC against arthroscopic evaluation as well as optimize and validate AdT1ρ and AdT2ρ mapping of cartilage in vivo. The findings showed that T1 and T2 relaxation time and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) were able to discriminate among different arthroscopic grades of cartilage lesions. However, arthroscopic findings and qMRI parameters were not correlated, supporting the viewpoint that qMRI may be able to elicit more comprehensive information on the quality of remaining cartilage tissue as compared to diagnostic arthroscopy, which detects cartilage loss. AdT1ρ and AdT2ρ mapping of cartilage in vivo were successfully implemented and validated on a clinical MRI system. AdT1ρ and AdT2ρ were able to overcome limitations of the existing methods (continuous wave spin-lock approach), which are challenging to implement on clinical settings for their susceptibility to field inhomogeneity and relatively high power deposition in tissue. The association of AdT1ρ and AdT2ρ with cartilage and bone marrow lesions and osteophytes was demonstrated. The findings indicate the utility of AdT1ρ and AdT2ρ mapping as potential biomarkers for evaluation of early cartilage degeneration in OA research and clinical applications. / Tiivistelmä Nivelrikko on tavallinen krooninen sairaus, joka huonontaa miljoonien ihmisten elämänlaatua ympäri maailman. Nivelrikossa nivelruston ja luun asteittain etenevä rappeuma voi aiheuttaa nivelkipua ja liikuntakyvyttömyyttä. Tällä hetkellä nivelrikkoon ei ole muuta tehokasta hoitokeinoa kuin tekonivelleikkaus. Tämä johtuu suuremmaksi osaksi tarkkojen biomarkkereiden puutteesta, joiden avulla voitaisiin kokeilla mahdollisia nivelrikon pysäyttäviä tai tautia parantavia lääkkeitä tai hoitokeinoja. Nykyisin nivelrikon diagnostiikassa käytetyimmät menetelmät ovat riittämättömiä sairauden alkuvaiheessa, ja ne tunnistavat vain sairauden loppuvaiheet. Kvantitatiivisilla magneettikuvausmenetelmillä pystytään erottamaan rappeutunut ja ehjä nivelrusto toisistaan ennen röntgenkuvissa havaittavia muutoksia. Nk. pyörivän koordinaatiston relaksaatioaikaparametrit ovat herkkiä havaitsemaan hidasta molekyyliliikettä, jolla on merkitystä kliinisissä sovelluksissa. Kokeellisissa olosuhteissa T1ρ- ja T2ρ-relaksaatioaikojen mittaaminen käyttäen adiabaattisia spin-lukkopulsseja (AdT1ρ ja AdT2ρ) on osoittautunut erityisen tarkaksi nivelruston rappeutumisen toteamiseksi verrattuna perinteisiin kvantitatiivisiin magneettikuvausmenetelmiin. Tämän väitöskirjan tavoitteena oli vertailla vakiintuneita nivelrikon kvantitatiivisia magneettikuvausmenetelmiä sekä optimoida ja validoida AdT1ρ- ja AdT2ρ-menetelmien käyttöä ihmisen ruston tutkimisessa. Tulokset osoittivat, että T1- ja T2-relaksaatioajat sekä varjoainetehosteinen nivelruston magneettikuvaus pystyivät erottelemaan niveltähystyksessä määritettyjä nivelrikon eri asteita. Kuitenkaan niveltähystyslöydökset ja kvantitatiiviset magneettikuvausparametrit eivät korreloineet viitaten kvantitatiivisen magneettikuvauksen kykyyn osoittaa tarkemmin jäljellä olevan ruston laatua verrattuna niveltähystykseen, jossa arvioidaan ruston puutosta. Nivelruston AdT1ρ- ja AdT2ρ-relaksaatioaikamittaukset onnistuttiin suorittamaan ja validoimaan vapaaehtoisilla koehenkilöillä kliinisellä magneettikuvauslaitteella. AdT1ρ ja AdT2ρ eivät kärsineet samoista puutteista kuin tavanomaiset jatkuva-aaltoiset spin-lukkomenetelmät, joka ovat herkkiä kenttäepähomogeenisuuksille ja aiheuttavat suuremman radiotaajuusaltistuksen. Tutkimuksessa osoitettiin AdT1ρ- ja AdT2ρ-mittausten ja luuödeemin sekä osteofyyttien välinen yhteys. Tulokset osoittivat, että AdT1ρ- ja AdT2ρ-mittaukset ovat potentiaalisia biomarkkereita varhaisen nivelruston rappeuman havaitsemiseksi tutkimus- ja kliinisessä käytössä.

Abstract Osteoarthritis is a common joint disease in the adult population characterized by degeneration and limited repair capability of articular cartilage. Cartilage degeneration is also associated with remodeling and sclerosis of the subchondral bone. The relative contributions of these processes are not fully understood partly because of a lack of proper biomarkers for the diagnosis and follow-up of the disease progress. Current diagnostic methods are too insensitive or subjective for reliable and early diagnosis of osteoarthritis. Novel magnetic resonance imaging (MRI) techniques can be used for indirect assessment of cartilage constituents. In addition, the imaging of the subchondral bone and osteochondral junction has become feasible, which has been very difficult with conventional MRI methods due to the very fast signal (T2) decay in those tissues. Quantitative MRI of cartilage involves measurement of relaxation time parameters (T1, T2, T1ρ, T2ρ, TRAFF, T1sat) and investigation of how the parameters reflect the properties of the cartilage. SWIFT (Sweep imaging with Fourier transform) is an MRI technique capable of imaging short T2 structures, enabling assessment of the osteochondral junction as well as the subchondral bone. The aim of this work was to investigate osteoarthritic changes occurring in articular cartilage and subchondral bone in experimental animal models of osteoarthritis and degenerated human specimens with quantitative MRI measurements and SWIFT imaging at 9.4 T. Moreover, the feasibility of the different quantitative MRI techniques in the assessment of osteoarthritic changes was studied. For reference, biomechanical, quantitative and qualitative histology, biochemical and micro-computed tomography measurements were conducted. Novel adiabatic T1ρ and T2ρ relaxation time parameters were more sensitive than conventional methods (T1, T2) or continuous wave T1ρ to both early degenerative changes in a rabbit model of cartilage degeneration and to spontaneous degeneration of human cartilage. SWIFT enabled assessment of the structural properties of the subchondral bone. Moreover, signal changes related to the degree of osteoarthritis were detected at the cartilage–bone interface with SWIFT. These methods may provide new tools for improving the diagnosis of early osteoarthritis. Further studies are needed to investigate the clinical feasibility of these MRI techniques. / Tiivistelmä Nivelrikko on yleinen nivelsairaus, johon ei tällä hetkellä ole parannuskeinoa. Nivelrikossa nivelrusto rappeutuu asteittain aiheuttaen lopulta kudoksen tuhoutumisen; samanaikaisesti myös rustonalaisessa luussa sekä rusto–luurajapinnassa tapahtuu muutoksia. Nivelrustokudoksen uusiutumiskyky on erittäin heikko, joten vauriot olisi hyvä havaita varhaisessa vaiheessa. Nivelrikon syntymekanismeja ei kuitenkaan vielä täysin ymmärretä, koska nykyiset seurantamenetelmät eivät ole riittävän tarkkoja taudin etenemisen tarkkailemiseksi. Magneettikuvausteknologian kehitys mahdollistaa kuitenkin nivelruston koostumuksen tarkastelun nivelen ulkopuolelta. Kvantitatiivisen magneettikuvauksen avulla (T1, T2, T1ρ, T2ρ, TRAFF, T1sat relaksaatioaikaparametrit) voidaan mitata epäsuorasti nivelruston koostumusta ja rakennetta. SWIFT (Sweep Imaging with Fourier Transform) on uusi lyhyen kaikuajan magneettikuvausmenetelmä, joka mahdollistaa myös erittäin lyhyen T2-relaksaatioajan omaavien kudosten, kuten rusto–luurajapinnan sekä rustonalaisen luun kuvaamisen. Työssä tutkittiin nivelrikossa syntyviä muutoksia nivelrustossa, rusto–luurajapinnassa ja rustonalaisessa luussa erilaisissa eläinmalleissa sekä ihmiskudoksessa. Lisäksi työssä tarkasteltiin eri magneettikuvaustekniikoiden herkkyyttä havaita muutokset näissä kudoksissa. Nivelruston ja rustonalaisen luun ominaisuuksien määrittelemiseen käytettiin verrokkimenetelminä biomekaanisia, histologisia sekä biokemiallisia mittauksia ja tietokonetomografiakuvauksia. Kvantitatiivisista magneettikuvausparametreista adiabaattinen T1ρ sekä adiabaattinen T2ρ osoittautuivat herkimmiksi havaitsemaan muutoksia varhaisen nivelrikon eläinmallissa sekä ihmiskudosnäytteissä. SWIFT-magneettikuvaustekniikka puolestaan mahdollisti sekä rustonalaisen luukudoksen tilan arvioinnin että nivelrikossa tapahtuvien muutosten havainnoinnin rusto–luurajapinnassa. Nämä menetelmät voivat mahdollistaa nivelrikon diagnosoinnin taudin varhaisessa vaiheessa, mutta lisätutkimuksia vaaditaan menetelmien soveltuvuudesta kliiniseen käyttöön.

Ce travail de thèse concerne les verres bioactifs purs et dopés pour des applications en tant que biomatériaux en site osseux. Ils sont synthétisés par fusion dans le système SiO₂-CaO-Na₂O-P₂O₅. Quatre éléments métalliques (Zn, Ti, Cu et Ag), présentant des caractéristiques chimiques et physiologiques intéressantes, ont été introduits dans la matrice vitreuse. Leur réactivité chimique et leur cytotoxicité ont été évalués lors de tests in vitro. L'introduction de ces éléments métalliques influe sur les caractéristiques thermiques des verres ainsi que sur la dissolution de la matrice vitreuse, la cinétique et la cristallisation de la couche d'hydroxyapatite. Une bonne prolifération cellulaire a été mise en évidence. En parallèle, une méthode de synthèse d'une vitrocéramique, présentant une microporosité, a été développée par réaction entre TiN et ZnO. Des essais in vitro ont montré un caractère bioactif après 60 jours d'immersion et une absence de cytotoxicité. Ce biomatériau a ensuite été implanté au niveau de la diaphyse fémorale de lapins. Différentes études structurales ont montré la résorption progressive du biomatériau jusqu'à 6 mois d'implantation. Des scaffolds chitosan / verre bioactif ont également été synthétisés et obtenus par lyophilisation. Ils ont été étudiés lors d'essais in vitro. Ils ont servi de support pour la vectorisation de gentamicine. Les résultats obtenus montrent que les teneurs en chitosan et en verre bioactif ont une influence sur la cristallisation de l'hydroxyapatite et le relargage du médicament. Les modèles mathématiques établis montrent que le temps de relaxation des scaffolds dépend de la concentration de départ en gentamicine. / This research work focuses on the pure and doped bioactive glasses for use as bone biomaterial. They are synthesized by the melting method in the system SiO₂-CaO-Na₂O-P₂O₅. Four metallic elements, presenting interesting chemical and physiological properties, have been introduced in the amorphous matrix. Their chemical reactivity and their cytotoxicity have been evaluated during in vitro assays in simulated body fluid and cell culture media. The introduction of these metallic elements influences their thermal characteristics, the glass matrix dissolution, the kinetic and the crystallization of the hydroxyapatite layer. A good cells proliferation have been showed. In parallel, a method of synthesis of a glass-ceramic, having a microporosity, have been developed by reaction between TiN and ZnO. In vitro assays have showed a bioactive character after 60 days of immersion and a non-cytotoxicity. This biomaterial was implanted in the femoral dyaphisis of rabbits. Different structural studies have showed the gradual resorption of the biomaterial up to 6 months of implantation. Finally, scaffolds chitosan/bioactive glass, obtained by freeze-drying, have also been studied during in vitro assays. They were used as support for the vectorization of gentamicin. The obtained results show that the content of chitosan and bioactive glass have an impact on the crystallization of hydroxyapatite et the release of drug. Mathematic models show that the relaxation time depend on the starting concentration of gentamicin.

This study investigates relaxation polarization in some dielectric components of tester UNISPOT S40 developed by company UNITES Systems a.s. Relaxation polarization in the PCB substrates and in tester’s cable insulation causes undesirable deceleration of some test steps. Relaxation polarization in selected PCB substrates and various cables are examined by method of dielectric relaxation spectroscopy in the frequency domain and by measurement of polarization or depolarization current.

The task of this thesis is to study the subject of perfusion analysis based on dynamic imaging with T2/T2* contrast. The focus was on the acquisition commonly used for DSC-MRI and especially in the acquisition pulse sequences that use images with different echo time, so called Multi-echo sequence. Principles of dynamic measurement by magnetic resonance imaging, the role of contrast agents and their influence on the relaxation times are described. It also describes the problems perfusion analysis, measurement and mathematical modeling parameters entering to the convolution dependency for getting perfusion parametersIn the experimental part is developed automatic algorithm to gain curves relaxation time T2 *. Next, the synthetic data are created and tested robustness estimate perfusion parameters against noise. In the next phase of work there are compared real scanned objects with using a conversion with T2 * and free of T2*. In the last phase of work is compared influence of length of used echo times on concentration curves and after perfusion analysis influence on resulting perfusion parameters.

Temperature-sensitive polymers or "smart" polymers are materials that undergo phase separation initiated by temperature change. Some of these polymers possess phase separation temperatures close to human body temperature (37 C), thus offering a wide range of potential applications in controlled drug release or gene delivery systems, bioseparations, tissue engineering, etc. Of the polymers with a phase separation temperature close to 37 C, poly(N- isopropylacrylamide) (PNIPAM) and poly(vinyl methyl ether) (PVME) are perhaps the most important and were selected as the subjects of this study. In this work, these two polymers have been examined in the presence of low molecular weight additives, and their colloidal stability evaluated using 1 H NMR (nuclear magnetic resonance) and time-resolved 1 H NMR spin-spin relaxation time T2 experiments. An improved model of the two exchangeable states was applied for a more detailed characterization of the phase separation process. The main focus of this study was to determine the influence of additives on the phase separation behavior of the polymers (phase separation temperature, width of transition, maximum number of polymer chains participating in phase separation), reversibility of the phase separation, dynamics of solvent molecules (water and additive),...

Gadolinium-based contrast agents (GBCAs) are in widespread use to enhance magnetic resonance angiography images for evaluating vascular pathology. However, there are safety concerns and limitations regarding the use of GBCAs. It has been shown that the magnetic resonance imaging (MRI) signal intensity (T1-weighted images) in some of the brain's tissues is higher for patients who had multiple exposures to GBCAs compared to patients who had never had exposure to GBCAs. This implies that GBCAs are not sufficiently removed from body such that GBCAs may potentially have long-term effects on the human body. These potential safety concerns have led to an increased interest in alternative contrast agents. Methemoglobin (metHb) and oxygen-free hemoglobin (HHb) are two forms of hemoglobin with paramagnetic properties. It has been shown that the T1-weighted signal intensity of blood is changed during MRI scans for metHb and HHb, leading to enhanced contrast of MRI images. The ability of metHb and HHb to change the signal intensity has led to the idea that they can be used as effective contrast agents. MetHb can be made by exposing oxyhemoglobin (oxyHb) to nitric oxide (NO) and HHb can be made by removing the oxygen from hemoglobin using nitrogen (N2). In this study, a new gas delivery system was developed to make metHb and HHb. The new gas delivery system was developed to have greater experimental control compared to the PermSelect hollow-fiber module that was used in preliminary studies to make metHb. The same system can be used to make HHb. Initial experiments showed significant amounts of undesired nitrite (NO2-) formation during metHb formation due to the presence of contaminants in the NO gas source. To minimize this problem, flow of NO from the gas source was bubbled in a sodium hydroxide solution in order to reduce the NO2- concentration. Following metHb formation, continuous delivery of NO also led to the formation of ferrous nitrosyl hemoglobin (HbIINO). MRI studies showed that HbIINO can also increase the signal intensity of an MRI image. It is unknown as to whether metHb, HHb, or HbIINO would be a stronger and more appropriate contrast agent and to what extent the T1-weighted signal is affected by the concentration. This study evaluated T1-weighted images of blood samples over a range of metHb and HHb concentrations, as well as HbIINO concentrations. Comparison of T1 values showed that metHb is the strongest contrast agent and that HHb is a relatively weak contrast agent. This study showed for the first time that HbIINO can provide a contrast effect, although not as strong as metHb but stronger than HHb. With metHb providing a viable contrast between 10-20%, metHb has the potential to be a safe and effective contrast agent since it can be naturally converted back to hemoglobin.

Kadmium telurid je velmi důležitý materiál jak základního, tak i aplikovaného výzkumu. Je to dáno zejména jeho výhodnými elektronickými, optickými a strukturními vlastnostmi, které ho předurčují pro náročné technické aplikace. Dnes se hlavně používá pro jeho vysoké rozlišení k detekci a X-záření. Hlavní výhodou detektorů na bázi CdTe je, že nepotřebují chlazení a mohou spolehlivě fungovat i při pokojové teplotě. To způsobuje efektivnější interakce fotonů než je tomu u Si nebo jiných polovodičových materiálů. Obsahem této práce byla analýza a interpretace výsledků získaných studiem šumových a transportních charakteristik CdTe vzorků. Měření ukázaly že odpor homogenní části CdTe krystalů mírně klesá při připojení elektrického pole na vzorku. Při změně teploty navíc dochází k odlišné reakci u CdTe typu p a n. Právě těmto efektům je v práci věnována pozornost. Pomocí šumové spektroskopie bylo zjištěno, že při nízkých frekvencích je u vzorků dominantní šum typu 1/f, zatímco při vyšších frekvencích je sledován generačně-rekombinační šum a tepelný šum. Všechny měřené vzorky vykazovaly mnohem vyšší hodnotu šumu na nízkých frekvencích než udává Hoogeova rovnice. Byly nalezeny a popsány zdroje nadbytečného šumu.

Es werden ab-initio Rechnungen des Supermagnetwiderstands-Effektes von Fe/Cr-Multilagen vorgestellt. Die Elektronenstruktur wurde im Rahmen einer LCAO-Superzellen-Rechnung bestimmt. Als Störung der idealen Schichtstruktur wurden Cr-Defekte in Fe angenommen, die durch spinabhängige Relaxationszeiten beschrieben werden. Die elektrischen Transportkoeffizienten wurden durch Lösung der linearisierten Boltzmann-Gleichung in Relaxationszeitnäherung unter Verwendung des Mott-schen Zweistrommodells berechnet. Bei den betrachteten Systemen variierte die Dicke der Fe-Schicht zwischen 3 und 9 Monolagen, die der Cr-Schicht zwischen 1 und 13 Monolagen. In Abhängigkeit von der Fe- bzw. Cr-Schichtdicke ergeben sich in Übereinstimmung mit den Experimenten charakteristische Oszillationen des Supermagnetwiderstandes. Es wird der Einfluß der Spinanisotropie der Streuung auf den Effekt untersucht. Insbesondere kann gezeigt werden, daß der Effekt auch für spinunabhängige Streuung existiert. / Ab-initio calculations of the Giant Magnetoresistance (GMR) for Fe/Cr multilayers are presented. The electronic structure of the Fe/Cr superlattice is calculated within an optimized LCAO scheme using the local spin density approximation. The scattering of the electrons by Cr impurities in an Fe environment is taken into account by spin dependent relaxation times. The transport is described quasiclassically by solving the linearized Boltzmann equation in relaxation time approximation. In agreement with experiments characteristic oscillations of the GMR are obtained in dependence on the Cr and Fe layer thickness. It can be shown, that the GMR can be reduced or increased by the spin anisotropy of the scattering, but the phenomenon still exists for spin-independent scattering.