Dans ce travail, les s´séquences Imagerie par Résonance Magnétique (IRM) radiales à temps d’écho ultra-court (UTE) sont analysées pour évaluer leur potentiel dans l’étude non-invasive de différents modèles expérimentaux de maladies pulmonaires chez la souris. Chez le petit animal, les séquences radiales UTE peuvent efficacement limiter l’impact négatif sur la qualité de l’image dû au déphasage rapide des spins causé par les nombreuses interfaces air/tissu. En plus, les séquences radiales UTE sont moins sensibles aux artefacts de mouvement par rapport aux séquences Cartésiennes classiques. En conséquence, chez le petit animal, les séquences radiales UTE peuvent permettre d’obtenir des images du poumon avec une résolution bien inférieure au millimètre avec des rapports signal/bruit importants dans le parenchyme pulmonaire, tout en travaillant en conditions physiologiques (animaux en respiration spontanée). Dans cette thèse, il sera démontré que les séquences d’IRM protonique UTE sont outils efficaces dans l’étude quantitative et non-invasive de différents marqueurs distinctifs de certaines pathologies pulmonaires d’intérêt général. Les protocoles développés serontsimples, rapides et non-invasifs, faciles à implémenter, avec une interférence minimale sur la pathologie pulmonaire étudiée et, en définitive, potentiellement applicables chez l’homme. Il sera ainsi démontré que l’emploi des agents de contraste, administrés via les voies aériennes, permet d’augmenter la sensibilité des protocoles développés. Parallèlement, dans cette thèse des protocoles suffisamment flexibles seront implémentés afin de permettre l’étude d’un agent de contraste paramagnétique générique pour des applications aux poumons. / In this work, ultra-short echo time (UTE) Magnetic Resonance Imaging (MRI) sequences are investigated as flexible tools for the noninvasive study of experimental models of lung diseases in mice. In small animals radial UTE sequences can indeed efficiently limit the negative impact on lung image quality due to the fast spin dephasing caused by the multiple air/tissue interfaces. In addition, radial UTE sequences are less sensitive to motion artifacts compared to standard Cartesian acquisitions. As a result, radial UTE acquisitions can provide lung images in small animals at sub-millimetric resolution with significant signal to noise ratio in the lung parenchyma, while working with physiological conditions (freely-breathing animals). In this thesis, UTE proton MRI sequences were shown to be efficient instruments to quantitatively investigate a number of hallmarks in longitudinal models of relevant lung diseases with minimal interference with the lung pathophysiology, employing easilyimplementable fast protocols. The synergic use of positive contrast agents, along with anadvantageous administration modality, was shown to be a valuable help in the increase of sensitivity of UTE MRI. At the same time, UTE MRI was shown to be an extremely useful and efficacious sequence for studying positive contrast agents in lungs

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.

Actuellement, des méthodes quantitatives de résonance magnétique nucléaire (RMN) offrent des biomarqueurs qui permettent la réalisation d’études longitudinales pour le suivi de l’évolution des maladies neuromusculaires et des essais thérapeutiques de manière non-invasive. A la différence de la dégénérescence graisseuse, les processus d’inflammation/œdème/nécrose et fibrose sont des signes d’activité des maladies et leurs quantifications constitueraient ainsi de biomarqueurs parfaitement adaptés pour le suivi thérapeutique. Ce travail de thèse a consisté à mettre en place des méthodologies quantitatives plus précises et adaptées à l’étude clinique du muscle pour : (i) détecter et quantifier des sites d’activité de maladies par la cartographie T2 de l’eau ; (ii) identifier les différents processus pathophysiologiques qui sont à l’origine des altérations du T2 ; et (iii) détecter et quantifier la fibrose musculaire. Nous avons implémenté deux méthodes pour la quantification du T2 de l’eau dans le muscle. La première est basée sur une séquence d’écho de spin du type CPMG, où les signaux provenant des protons des lipides et de l’eau sont acquis simultanément et séparés à postériori par un traitement tri-exponentiel qui exploite la différence entre les T2 qui caractérisent les signaux de l’eau et de la graisse. La deuxième technique est basée sur une séquence de « partially spoiled steady state free precession (pSSFP) ». Différemment de la première technique qui nécessite un traitement assez élaboré sur des images acquises à 17 temps d’écho différents, dans la pSSFP la cartographie T2 est extraite à partir de deux séries de données 3D. L’acquisition 3D est compatible avec des techniques de sélection spectrale de l’eau, ce qui évite la contamination par les signaux des lipides. Les deux méthodes ont été validées expérimentalement chez des malades et des sujets sains et ont démontré leur capacité à détecter et quantifier des sites d’activité de maladies. Ces deux travaux font l’objet de deux publications dans des journaux scientifiques internationaux : 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. Malgré le fait de permettre la détection des sites d’activité de maladies, la mesure mono-exponentielle du T2 de l’eau par imagerie reste non-spécifique vis-à-vis des processus physiologiques à l’origine de l’augmentation du T2. Il est connu que la relaxation T2 du muscle squelettique n’est pas mono-exponentielle. Cela est interprété comme une conséquence de la compartimentation anatomique de l’eau tissulaire. Nous avons mis au point une méthode pour l’acquisition localisée de données CPMG. Cette technique permet l’acquisition des données dans des conditions nécessaires pour la réalisation de traitements multi-exponentiels précis. Ce travail nous a permis d’établir un modèle de compartimentation qui explique parfaitement la relaxation T2 dans le muscle. Il a fait l’objet d’un article publié dans le « Biophysical Journal » (Araujo, Fromes & Carlier 2014. New Insights on skeletal muscle tissue compartments revealed by T2 NMR relaxometry. (In press)). Les essais réalisés chez des sujets malades suggèrent un grand potentiel pour l’application de la méthode dans des études cliniques. La formation de la fibrose commence avec une accumulation excessive de tissu conjonctif intramusculaire (TCIM). Nous avons exploité la technique « Ultrashort Time-to-Echo » (UTE) pour essayer de détecter et caractériser le signal du TCIM. Dans une première étude, nous avons caractérisé in vivo une composante à T2 court (~500 µs) dans le muscle, et nous avons trouvé des indices qui suggèrent qu’elle représente le TCIM. Dans une deuxième étude, nous avons mis au point une méthodologie qui a permis d’imager cette composante à T2 court dans le muscle pour la première fois. / 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.

In the light of growing concerns regarding the quality of higher education after a period of rapid expansion, in 2003, the Chinese government launched the Undergraduate Teaching Evaluation (UTE), the first nation-wide evaluation of universities. In 2008, the UTE was replaced by the Quality Project, which signalled a change in its quality assurance approach, with a move from evaluations to the issuing of awards. In order to investigate the impact of the two national quality assurance policies, along with the impact of two long-standing internal quality assurance mechanisms employed by universities - class observation and student evaluation of teachers - on teaching, the researcher adopted policy analysis and a case study approach. Three different universities in the same region were selected as cases. Semi-structured interviews with 56 heads of department and teachers across three departments at each university were conducted. National and university policy documents, as well as interview data, were analysed thematically in the light of concepts derived from the political sciences, namely Knoepfel et al.'s (2007; 2011) framework for policy analysis and Schneider and Ingram's (1990) classification of policy tools. University policies and interview data revealed the patterns of impact of these two quality assurance policies. Faced with the UTE inspection, universities shifted their focus from assuring the quality of teaching to achieving good results in the exercise and therefore engaging in 'game-playing'. In order to ensure good UTE results, universities even resorted to the manipulation of data. University policies resulting from the UTE required teachers to produce standardised documents and to follow particular procedures. The majority of interviewed teachers regarded the impact of the UTE with cynicism, seeing it as a waste of time and effort, an interference with academic freedom, and believing it had the effect of undermining ethics. However, some teachers reported as positive impact of the fact that the UTE helped to keep teachers disciplined, and that it provided an impetus for ensuring teaching quality. Interview data showed that the Quality Project awards only had an impact on the award winners, who perceived the incentives on offer to be substantial. These award winners considered the acknowledgement given by the awards and the information obtained through reflection and good examples as valuable impacts. However, the Quality Project awards did not have impact on non-award winners, i.e. the majority of teachers. This study revealed that in order to have impact the institutional practices of class observation and the student evaluation of teachers relied on a number of conditions being in place. These practices had impact when the stakes were high or when university teachers received valid and reliable feedback. Whilst high stakes were found to lead to mixed impact, valid and reliable feedback contributed to the improvement of teaching. This study contributes to the understanding of the impact of quality assurance policies and mechanisms on teaching in Chinese higher education, an area that has not yet been the subject of significant empirical research. Covering the two major quality assurance policies in recent years, and also the institutional mechanisms teachers face, this research was able to capture the interdependence between these policies. No such research has previously been conducted in the context of Chinese higher education. In regard to the theoretical aspect of the research, the empirical evidence that was collected and a comprehensive review of other empirical research enabled the development of an Impact Framework. The Impact Framework identified patterns in the impact of various quality assurance policy tools and revealed their inherent strengths and weaknesses. Hence, the Impact Framework can serve in the future as an important reference for policy-makers who are seeking to design and implement effective quality assurance policy tools.

This thesis deals with the cartilage imaging using magnetic resonance. At first, there is mentioned physical principle of the magnetic resonance phenomenon and the most commonly used excitation sequences, followed by the description of the 9.4 T MR imaging system Bruker BioSpec 94/30 USR, which was used for measurement in the practical part. The next part is dedicated to the composition of cartilages and describes the temporomandibular joint, due to its suitability as an object for cartilage imaging. The series of MR scans of temporomandibular joint were taken with different acquisition parameters and evaluated by program designed through the MATLAB software. The program can be used for viewing scanned images, evaluating their contrast and determining the T1 relaxation time of the tissues by creating T1 maps.