Current quantitative nuclear magnetic resonance (NMR) technics offer biomarkers that allow performing non-invasive longitudinal studies for the follow up of therapeutic trials in neuromuscular disorders (NMD). In contrast to fat degeneration, the mechanisms of inflammation/oedema/necrosis and fibrosis are characteristic signs of disease activity, which makes their quantification a promising source of crucial biomarkers for longitudinal studies. This thesis work consisted on the implementation of more precise quantitative NMR methods adapted to the clinical study of skeletal muscle (SKM) for : (i) detection and quantification of sites of disease activity by T2-mapping of muscle water ; (ii) investigation of the different pathophysiological mechanisms underlying T2 alterations ; and (iii) Detection and quantification of muscle fibrosis. We implemented two methods for T2 mapping of muscle water. The first one is based on a multi-spin-echo sequence du type CPMG. In this method the 1H-NMR signals from water and lipids are acquired simultaneously. The acquired data are fitted to a tri-exponential model, in which water and fat signals are separated by exploring the T2 difference between water and fat. This method allows extraction of muscle water T2-value in the presence of fat infiltration. The second method is based on a " partially spoiled steady state free precession " (pSSFP) sequence. In contrast to the first method, which demands a sophisticated post-treatment of images acquired at 17 different echo-times, with the pSSFP a T2-mapping is extracted from two 3D data sets. 3D acquisition is compatible with spectrally selective water excitation, which eliminates signal contribution from lipids. Both methods were validated experimentally on patients and healthy subjects. The results demonstrated their capacity to detect and quantify disease activity sites. This 2 works have been published in two international journals : Azzabou, de Sousa, Araujo, & Carlier, 2014. Journal of Magnetic Resonance Imaging. DOI 10.1002/jmri.24613 (in press); et de Sousa, Vignaud, Araujo, & Carlier . 2012. Magnetic Resonance in Medicine. 67:1379-1390. Although it was shown to reveal disease activity, mono-exponential T2 of muscle water is non-specific to what concerns the mechanisms underlying its alterations. It has been long known that T2 relaxation in SKM tissue is multi-exponential. This is currently accepted to reveal anatomical compartmentation of myowater. We implemented a method for localized spectroscopic CPMG acquisition. CPMG data respect echo-time sampling and signal to noise ration limits for allowing robust multiexponential analysis. This work allowed us to establish a compartmentation model that perfectly explains the multi-exponential T2 relaxation observed in SKM tissue. This work was published in the " Biophysical Journal " (Araujo, Fromes & Carlier 2014. New Insights on skeletal muscle tissue compartments revealed by T2 NMR relaxometry. (In press)). Pilot studies performed in patients show promising results and suggest potential application of the method in clinical studies. Fibrosis starts with an excessive accumulation of intramuscular connective tissue (IMCT). We have explored the " Ultrashort time to echo " (UTE) method with the aim to detect and characterize the signal from IMCT. In a first study we characterized in vivo a short T2 component (~500 µs) in SKM, and we collected evidences suggesting that this component might reflect IMCT. Then we implemented a methodology that allowed imaging this short component in SKM tissue for the first time.

Este trabalho tem como objetivo o estudo da influência do boro na fase αNb5Si3 (Fase T2) a baixas temperaturas analisando suas propriedades elétricas e magnéticas. Para o estudo deste tema as amostras foram preparadas, seguindo a estequiometria Nb5Si3-xBx, via metalurgia do pó e também por fusão a arco, com x dentro do intervalo limitado por 0  X  1,0. Estas amostras foram analisadas através de difratometria de raios x, microscopia eletrônica de varredura, magnetização, transporte elétrico e medidas calorimétricas em baixa temperatura. As medidas das propriedades elétricas e magnéticas destas fases mostram que a substituição de boro por silício induz supercondutividade na fase T2. O caráter volumétrico da transição supercondutora é confirmado pela medida de capacidade calorífica. Assim, este trabalho é o primeiro a mostrar uma nova família de materiais supercondutores que cristalizam na estrutura protótipo Cr5B3. / This work to study the influence of boron during low temperature αNb5Si3 (T2 phase) analyzing their electrical and magnetic properties. For the study of this subject the samples were prepared, following the stoichiometry Nb5Si3-xBx via powder metallurgy and also by arc melting process, with x within the range limited by 0X1.0. These samples were analyzed by X-ray diffraction, scanning electron microscopy, magnetization, electrical transport and calorimetric measurements of low temperature. Measurements of electrical and magnetic properties of these phases show that the substitution of boron by silicon induces superconductivity at the T2 phase. The bulk nature of superconducting transition is confirmed by heat capacity measurement. This study is the first to show a new family of superconducting materials that crystallize in the Cr5B3 prototype structure.

A tecnologia dos semicondutores inorgânicos tem dominado a indústria eletrônica por muitos anos. No entanto, com a descoberta dos polímeros condutores um esforço considerável tem sido dedicado ao estudo e às aplicações tecnológicas desses materiais em dispositivos eletrônicos, dando início a um novo ramo da eletrônica: a Eletrônica Orgânica (EO). Uma das grandes vantagens da EO reside nos métodos de processamento. Os materiais orgânicos são facilmente processados em solução, portanto permite o uso de diversas técnicas de deposição, como por exemplo, as técnicas de impressão. Dentre as técnicas de impressão, a jato de tinta é a que mostra ser mais adequada à impressão de circuitos. Ela permite depositar volumes de soluções (ou suspensões) da ordem de picolitros em cada gota mantendo padrões bem definidos. Além disso, elimina o uso de máscaras, ocasionando diminuição nos custos e desperdício de material e, por ser um método de deposição tipo não-contato, minimiza possíveis contaminações. Esta tese dedicou-se, dentro desse contexto, ao domínio da técnica de jato de tinta para a confecção de transistores de efeito de campo orgânico (OFETs) tipo p e tipo n, e com aplicação em um inversor lógico unipolar. Os OFETs impressos usaram a arquitetura top gate/bottom contact (TG/BC. Os filmes semicondutores foram formados por várias linhas impressas sobre a região dos eletrodos fonte e dreno. Para os OFETs tipo p foi utilizado o semicondutor Poli(3-hexiltiofeno) régio-regular (rr-P3HT). Foram fabricados OFETs tipo p com a impressão de linhas utilizando os quatro diferentes padrões de deposição da impressora Autodrop. OFETs tipo p com mobilidade em torno de 3x10-3 cm2/V.s e razões Ion/Ioff da ordem de 103 foram obtidos utilizando um padrão de deposição paralelo e outro perpendicular a fonte e dreno. Para os OFETs tipo n o semicondutor usado foi o Poli{[N,N\'-bis(2-octildodecil)-naftaleno-1,4,5,8-bis(dicarboximida)-2,6-diil]-alt-5,5\'-(2,2\'-bitiofeno)]} (P(NDI2OD-T2)). Dentre os OFETs tipo n impressos os melhores apresentaram mobilidades em torno de 10-2 cm2/V.s e razões Ion/Ioff de aproximadamente 5x102. Ambos os OFETs impressos foram aplicados em inversores lógicos digitais unipolares com ganhos maiores que 1. / The technology of inorganic semiconductors has dominated the industry of electronics for many years. However, since the discovery of conductive polymers considerable effort has been devoted to studies and technological applications of these materials in electronic devices, starting a new branch of electronics: Organic Electronics (OE). One of the great advantages of OE lies in the processing methods. The organic materials are easily handled in solution, thus allows the use of various deposition techniques, as for example the printing techniques. Among the techniques of printing, inkjet is showing to be more suitable for printing circuits. It allows you to deposit solutions (or suspensions) volumes on the order of picoliters in each drop, performing well-defined patterns. Furthermore, it eliminates the use of masks, resulting in reduced costs and material waste. This thesis is dedicated to the field of inkjet technique, specifically for the fabrication of organic field-effect transistors (OFETs), p-type and n-type, and application in a unipolar logic inverter. Printed OFETs used architecture top gate/bottom contact (TG/BC). The semiconductor films were formed by several printed lines on the region of the source and drain electrodes. For p-type OFETs we used poly (3-hexylthiophene ) regio-regular (rr-P3HT) as semiconducting material. The p-type OFETs were fabricated using the four different patterns of deposition of the printer Autodrop. These OFETs showed mobility around 3x10-3 cm2/V.s and Ion/Ioff ratio of the order of 103 for the deposition pattern parallel and perpendicular to source and drain. For the n-type OFETs the semiconductor used was Poly{[N,N\'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5\'-(2,2\'-bithiophene)]} (P(NDI2OD-T2)). Among the printed n-type OFETs the best showed mobility around of 10-2 cm2/V.s and Ion/Ioff ratio of the order of 5x102. Both printed OFETs were applied in unipolar digital logic inverters, with gains greater than 1.

Este trabalho tem como objetivo o estudo da influência do boro na fase αNb5Si3 (Fase T2) a baixas temperaturas analisando suas propriedades elétricas e magnéticas. Para o estudo deste tema as amostras foram preparadas, seguindo a estequiometria Nb5Si3-xBx, via metalurgia do pó e também por fusão a arco, com x dentro do intervalo limitado por 0  X  1,0. Estas amostras foram analisadas através de difratometria de raios x, microscopia eletrônica de varredura, magnetização, transporte elétrico e medidas calorimétricas em baixa temperatura. As medidas das propriedades elétricas e magnéticas destas fases mostram que a substituição de boro por silício induz supercondutividade na fase T2. O caráter volumétrico da transição supercondutora é confirmado pela medida de capacidade calorífica. Assim, este trabalho é o primeiro a mostrar uma nova família de materiais supercondutores que cristalizam na estrutura protótipo Cr5B3. / This work to study the influence of boron during low temperature αNb5Si3 (T2 phase) analyzing their electrical and magnetic properties. For the study of this subject the samples were prepared, following the stoichiometry Nb5Si3-xBx via powder metallurgy and also by arc melting process, with x within the range limited by 0X1.0. These samples were analyzed by X-ray diffraction, scanning electron microscopy, magnetization, electrical transport and calorimetric measurements of low temperature. Measurements of electrical and magnetic properties of these phases show that the substitution of boron by silicon induces superconductivity at the T2 phase. The bulk nature of superconducting transition is confirmed by heat capacity measurement. This study is the first to show a new family of superconducting materials that crystallize in the Cr5B3 prototype structure.

Magnetic Resonance Imaging (MRI) is an important diagnostic tool for imaging soft tissue without the use of ionizing radiation. Moreover, through advanced signal processing, MRI can provide more than just anatomical information, such as estimates of tissue-specific physical properties. Signal processing lies at the very core of the MRI process, which involves input design, information encoding, image reconstruction, and advanced filtering. Based on signal modeling and estimation, it is possible to further improve the images, reduce artifacts, mitigate noise, and obtain quantitative tissue information. In quantitative MRI, different physical quantities are estimated from a set of collected images. The optimization problems solved are typically nonlinear, and require intelligent and application-specific algorithms to avoid suboptimal local minima. This thesis presents several methods for efficiently solving different parameter estimation problems in MRI, such as multi-component T2 relaxometry, temporal phase correction of complex-valued data, and minimizing banding artifacts due to field inhomogeneity. The performance of the proposed algorithms is evaluated using both simulation and in-vivo data. The results show improvements over previous approaches, while maintaining a relatively low computational complexity. Using new and improved estimation methods enables better tissue characterization and diagnosis. Furthermore, a sequence design problem is treated, where the radio-frequency excitation is optimized to minimize image artifacts when using amplifiers of limited quality. In turn, obtaining higher fidelity images enables improved diagnosis, and can increase the estimation accuracy in quantitative MRI.

Title: Biomechanical response of the knee meniscus to the axial loads Work Title: The quantification of the structural changes in deep layer of the knee meniscus using the standardized axial loading Purpose: Due to the internal structure of the knee joint, the ability to characterize and quantify the dynamic response of the meniscal tissue directly in vivo is highly problematic. The main purpose of this study was to investigate the behavior of the meniscus under loading conditions, using parametric MR imaging. Methods: Subjects with no history of knee pain or meniscal problems were included in the study (mean age 27.8 ± 1.3 years). To obtain values of relaxation times T2* in the meniscus, the vTE sequence was used with 10 echoes ranging from 0.8 to 10.1 ms. This has resulted in minimizing the echo time, which is an advantage when differentiating meniscal tissue from surrounding components. First of all, an unloaded limb was scanned and immediately after, the limb loaded half of the person's weight was measured repeatedly in 4 consecutive scans. A custom - made diamagnetic apparatus was developed to simulate stress conditions on the lower limb in a conventional MR scanner. At each 6:10 min measurement, the knee joint was scanned in 64 sections, each image displaying a 1.3 mm section.The two -...

L’IRM est de plus en plus utilisée pour diagnostiquer et évaluer un très grand nombre de pathologies. Cette technique présente cependant deux inconvénients majeurs. En effet, les examens restent encore très longs (notamment en imagerie 3D) et la quantification est très difficile par rapport à d’autres modalités comme la tomographie par émission de positons. L’objectif de ce travail de thèse a été de diminuer significativement les temps d’acquisition nécessaires pour l’imagerie volumique et de développer des techniques quantitatives robustes, permettant d’effectuer des suivis longitudinaux.Pour cela, des méthodes innovantes ont été développées à très haut champ magnétique (7T) et validées sur des modèles murins sains et pathologiques. Trois développements majeurs sont ressortis de cette thèse. Tout d’abord, une mesure rapide des temps de relaxation longitudinale (T1) a été développée.Cette méthode basée sur une approche Look-Locker a été couplée avec un échantillonnage en empilement de spirales et a permis d’obtenir au niveau cardiaque des cartes T1 en 3D sur des souris saines et des modèles d’infarctus du myocarde en moins de 15 minutes. Ensuite, une approche dite« spiral-in » a été couplée avec une méthode de multi-échos de spin afin d’accélérer la mesure des temps de relaxation transversale (T2). Cette méthode a permis d’obtenir des cartes T2 en 3D sur des cerveaux de souris saines et métastatiques en moins de 20 minutes. Enfin, une approche hybride couplant les avantages de l’acquisition spiralée et ceux de l’échantillonnage radial a été développée.Cette méthode a été couplée avec une technique de Golden-Angle pour échantillonner aléatoirement l’espace de Fourier et a permis pour la première fois de visualiser une angiographie 3D d’un foie de souris en respiration libre en moins de 12 minutes. Toutes les méthodes développées dans ce travail ont été validées au niveau de leur robustesse et démontrent que l’IRM peut être une technique à la fois rapide et quantitative. Ces développements pourront être transférés vers la clinique dans de futurs travaux. / MRI is more and more used to diagnose and assess a wide range of pathologies. However, this technique is still limited by two disadvantages. Indeed, the acquisition times are too long(especially in 3D) and the quantification is still difficult compared to other techniques like positron emission tomography. The aim of this PhD project was to significantly reduce acquisition times required for 3D imaging and to develop robust quantitative techniques allowing longitudinal studies.To these ends, innovative methods have been developed at very high magnetic field (7T) and validated on healthy and diseased mouse models. Three major developments arose from this work. Firstly, a fast measurement of the longitudinal relaxation time (T1) has been developed. This method based on a Look-Locker approach was coupled with a sampling using stack-of-spirals and allowed to get T1 mapsin 3D in healthy and myocardial infarction models in less than 15 minutes. Then, a "spiral-in" approach was coupled with a multi spin echoes acquisition to accelerate the measurement of the transverse relaxation time (T2). This method allowed to get T2 maps in 3D of healthy and metastatic mouse brains in less than 20 minutes. Finally, a hybrid approach combining the advantages of the spiral acquisition with those of the radial sampling has been developed. This method has been coupled with a Golden-Angle technique for randomly sampling the k-space and allowed for the first time to display a 3Dangiography of a mouse liver in free breathing in less than 12 minutes. All the protocols developed inthis PhD project were validated in terms of robustness and showed that MRI can be a technique both rapid and quantitative. These developments will be transferred to the clinic in future works.

Brassica napus est une des cultures oléagineuse majeure dans le monde. En raison de sa faible efficacité d’utilisation de l’azote (NUE) comparée aux autres grandes cultures, la gestion de cette ressource présente un objectif écologique et économique majeur pour cette culture. La remobilisation des nutriments des organes sources vers les organes puits est une composante de la NUE qui se déroule durant la sénescence et qui est associée aux processus de recyclages métaboliques et à des modifications de la structure foliaire. L’objectif de cette thèse était de comprendre et de quantifier ces modifications structurales afin d’évaluer à travers ces processus les capacités de remobilisation du colza en fonction de son génotype et de son statut nutritionnel (eau et azote). La structure foliaire a été étudiée grâce à la relaxométrie RMN qui donne accès au statut et à la distribution de l’eau au niveau cellulaire. Ces travaux de thèse ont mis en évidence que la distribution des temps de relaxation transversale (T2) dépend non seulement de la structure cellulaire, mais aussi de l’organisation tissulaire. Cette étude a aussi mis en évidence le processus d’élargissement cellulaire et d’hydratation pendant la sénescence, spécifiquement dans le parenchyme palissadique. Il a été également démontré que le signal RMN reflète la déstructuration progressive se déroulant durant la sénescence au niveau subcellulaire et est un marqueur de sénescence précis permettant de suivre le développement de la feuille. De plus, le statut nutritionnel de la plante modifié par les carences azotées ou le stress hydrique, impacte grandement la sénescence séquentielle et les conséquences en termes d’efficacité de la remobilisation peuvent être suivies par RMN. Ce travail a permis de renforcer les connaissances sur la structure et le fonctionnement de la feuille au niveau tissulaire et cellulaire. De plus, il a été démontré que le signal de relaxométrie RMN donne accès à des informations sur la structure foliaire inaccessible par des méthodes courantes. Une des principales applications de ce travail serait le phénotypage, particulièrement la sélection de génotypes caractérisés par une forte efficacité de remobilisation en particulier en cas de carence azoté ou de stress hydrique. / Brassica napus is one of the major oil crops of the world. Due to its low NUE (Nitrogen Use Efficiency) compared to other species, Nitrogen management presents a major economic and environmental goal for improvement of that crop production. As a component of NUE, nutrient remobilization from source to sink tissues takes place mainly during the leaf senescence and is associated to metabolic recycling processes and modification of the cellular organization and structure. The aim of this work was therefore to understand and estimate the amplitude of these structural modifications with the objective to appreciate through these processes remobilization performance according to oilseed rape genotypes and nutritional status in terms of nitrogen and water supply. The leaf structure was investigated through NMR relaxometry, providing access to cellular water status and distribution. The present work demonstrated that the transverse relaxation time (T2) distribution depends on both leaf tissue structure and cellular compartmentalization. The study revealed a process of cell enlargement and hydration during leaf senescence, specifically in the palisade parenchyma and showed that the T2 relaxation time was able to discriminate parenchyma tissues at an early phase of senescence induction. Moreover, the NMR relaxometry signal was shown to reflect specific chronological loss of sub-cellular structuring all along the senescence process progression and was demonstrated to be an accurate non-invasive monitoring method of leaf development. Finally, plant nutrition status experienced through nitrogen and water availability limitation has been demonstrated to strongly affect regular sequential leaf senescence. Consequences on remobilization efficiency by stress conditions have been also assessed through the NMR signal. This work has improved the understanding of leaf structure and functioning at the cell and tissue levels after the onset and during the progression of senescence. Moreover, it was demonstrated that NMR relaxometry provides access to leaf structural information that are not accessible with currently used techniques for plant structural investigations. One of the main applications would be for plant phenotyping, especially for selecting genotypes with higher nutrient remobilization efficiency especially under environmental stresses like nitrogen and water limitations for sustainable oil and protein production.

A tecnologia dos semicondutores inorgânicos tem dominado a indústria eletrônica por muitos anos. No entanto, com a descoberta dos polímeros condutores um esforço considerável tem sido dedicado ao estudo e às aplicações tecnológicas desses materiais em dispositivos eletrônicos, dando início a um novo ramo da eletrônica: a Eletrônica Orgânica (EO). Uma das grandes vantagens da EO reside nos métodos de processamento. Os materiais orgânicos são facilmente processados em solução, portanto permite o uso de diversas técnicas de deposição, como por exemplo, as técnicas de impressão. Dentre as técnicas de impressão, a jato de tinta é a que mostra ser mais adequada à impressão de circuitos. Ela permite depositar volumes de soluções (ou suspensões) da ordem de picolitros em cada gota mantendo padrões bem definidos. Além disso, elimina o uso de máscaras, ocasionando diminuição nos custos e desperdício de material e, por ser um método de deposição tipo não-contato, minimiza possíveis contaminações. Esta tese dedicou-se, dentro desse contexto, ao domínio da técnica de jato de tinta para a confecção de transistores de efeito de campo orgânico (OFETs) tipo p e tipo n, e com aplicação em um inversor lógico unipolar. Os OFETs impressos usaram a arquitetura top gate/bottom contact (TG/BC. Os filmes semicondutores foram formados por várias linhas impressas sobre a região dos eletrodos fonte e dreno. Para os OFETs tipo p foi utilizado o semicondutor Poli(3-hexiltiofeno) régio-regular (rr-P3HT). Foram fabricados OFETs tipo p com a impressão de linhas utilizando os quatro diferentes padrões de deposição da impressora Autodrop. OFETs tipo p com mobilidade em torno de 3x10-3 cm2/V.s e razões Ion/Ioff da ordem de 103 foram obtidos utilizando um padrão de deposição paralelo e outro perpendicular a fonte e dreno. Para os OFETs tipo n o semicondutor usado foi o Poli{[N,N\'-bis(2-octildodecil)-naftaleno-1,4,5,8-bis(dicarboximida)-2,6-diil]-alt-5,5\'-(2,2\'-bitiofeno)]} (P(NDI2OD-T2)). Dentre os OFETs tipo n impressos os melhores apresentaram mobilidades em torno de 10-2 cm2/V.s e razões Ion/Ioff de aproximadamente 5x102. Ambos os OFETs impressos foram aplicados em inversores lógicos digitais unipolares com ganhos maiores que 1. / The technology of inorganic semiconductors has dominated the industry of electronics for many years. However, since the discovery of conductive polymers considerable effort has been devoted to studies and technological applications of these materials in electronic devices, starting a new branch of electronics: Organic Electronics (OE). One of the great advantages of OE lies in the processing methods. The organic materials are easily handled in solution, thus allows the use of various deposition techniques, as for example the printing techniques. Among the techniques of printing, inkjet is showing to be more suitable for printing circuits. It allows you to deposit solutions (or suspensions) volumes on the order of picoliters in each drop, performing well-defined patterns. Furthermore, it eliminates the use of masks, resulting in reduced costs and material waste. This thesis is dedicated to the field of inkjet technique, specifically for the fabrication of organic field-effect transistors (OFETs), p-type and n-type, and application in a unipolar logic inverter. Printed OFETs used architecture top gate/bottom contact (TG/BC). The semiconductor films were formed by several printed lines on the region of the source and drain electrodes. For p-type OFETs we used poly (3-hexylthiophene ) regio-regular (rr-P3HT) as semiconducting material. The p-type OFETs were fabricated using the four different patterns of deposition of the printer Autodrop. These OFETs showed mobility around 3x10-3 cm2/V.s and Ion/Ioff ratio of the order of 103 for the deposition pattern parallel and perpendicular to source and drain. For the n-type OFETs the semiconductor used was Poly{[N,N\'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5\'-(2,2\'-bithiophene)]} (P(NDI2OD-T2)). Among the printed n-type OFETs the best showed mobility around of 10-2 cm2/V.s and Ion/Ioff ratio of the order of 5x102. Both printed OFETs were applied in unipolar digital logic inverters, with gains greater than 1.

Diploma thesis explores the possibility of using diffusion-weighted images in medicine. The paper is a brief physical principle of operation of the magnetic resonance as a tool for non-destructive imaging of the internal structure of substances, the principle of the display contrast as T1, T2 and diffusion weighted images, the course of the sequence for obtaining images with different contrast. Medicine is faced with the problem of classification of pathological tissue in the brain. Contrast diffusion-weighted images does not visually determine the shape of pathological tissue in the form of a tumor or edema. With the T1 and T2 weighted images were calculated mask corresponding tumor and edema, that have been applied to the diffusion-weighted images. Images of the tumor and edema have been subjected diffusivity measurements and statistical evaluation for the purpose of classifying the type of tumor. Investigations were seven findings glioma and metastatic five awards. The research was focused on classifying pathological tissue.