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L’Imagerie par Résonance Magnétique (IRM) est une belle application de la physique et constitue sans aucun doute l’une des techniques les plus performantes d’imagerie médicale. Basée sur le phénomène de la Résonance Magnétique Nucléaire (RMN) du proton contenu dans les molécules d’eau, l’IRM permet d’investiguer en coupes les tissus mous du corps, sur base de contrastes différents. La méthode est non-invasive et n’utilise pas de radiations ionisantes. En plus des données morphologiques, l’IRM permet également d’obtenir des informations fonctionnelles et physiologiques. De nos jours, plus de 10 000 unités IRM existent dans le monde et des millions d’examens sont réalisés chaque année. La technique est en constant développement et le domaine de recherches est multidisciplinaire. Il concerne aussi bien les développements méthodologiques (imagerie rapide, imagerie de diffusion, etc.) que technologiques (imagerie à haut champ, systèmes de gradients à commutation rapide, etc.), le point central des recherches étant l’amélioration de la qualité des images et la diminution du temps d’acquisition. Ceci implique l'optimisation des différentes séquences IRM (séries d'impulsions radiofréquence et de gradients de champ magnétique) tenant compte des contraintes imposées par le matériel, ainsi que le développement et l'optimisation du matériel lui-même. Cette thèse est consacrée au design avancé des séquences d’impulsions et contribue donc à l'optimisation des schémas d’acquisition en IRM. En particulier, le présent travail est focalisé sur la compréhension et l’amélioration d’un certain type de séquences rapides, employant des échos de gradients : les séquences Steady-State Free Precession (SSFP) et plus précisément les séquences dites balanced-SSFP. Dans ce genre de schéma d’acquisition, le système est excité rapidement et périodiquement, conduisant à l’établissement d’un état stationnaire de l’aimantation. La première partie de la thèse est consacrée à une analyse approfondie des propriétés du signal dans une séquence balanced-SSFP, à la fois à l’état stationnaire et à l’état transitoire. Ensuite, de nouveaux schémas d’acquisition sont développés sur base de calculs analytiques et de simulations numériques et sont ensuite testés expérimentalement. D’une part, une manipulation de l’état stationnaire est présentée en vue de supprimer le signal de la graisse sur les images (qui peut être gênant pour le diagnostic de certaines lésions ou maladies). D’autre part, l’application d’une phase de préparation en vue d’obtenir un contraste basé sur le degré de diffusion des molécules d’eau dans les tissus est analysée en détails, afin d’améliorer la qualité d’image produite par des séquences de diffusion existantes. La présente thèse constitue donc un travail de recherches théoriques et expérimentales, allant de la conception de nouveaux schémas d’acquisition à leur expérimentation sur volontaires, en passant par leur implémentation sur un imageur IRM. Ce travail a été réalisé au sein de l’Unité d’IRM – Radiologie de l’Hôpital Erasme, sous la direction de Thierry Metens, Docteur en Sciences et Physicien IRM.

Heart failure is a complex clinical syndrome in which the heart cannot pump sufficient blood and nutrients to the organs in the body. Increasingly, alterations in cardiac energetics are being implicated as playing an important role in the pathogenesis of heart failure. An understanding of specific metabolic switches which occur during the development of heart failure in patients would be greatly beneficial as a new diagnostic method and for the development of new therapies for patients with failing hearts. This thesis deals with the non-invasive assessment of metabolism in the heart. New magnetic resonance imaging (MRI) methods for metabolic characterization of the heart using hyperpolarized carbon-13 MRI are presented. Spatially resolved images of hyperpolarized 13C substrates and their downstream products can provide insight into real-time metabolic processes occurring in vivo, within minutes of injection of a pre-polarized 13C-labeled substrate. Conventional 3D spectroscopic acquisitions require in excess of 100 excitations, making it challenging to acquire full cardiac and respiratory-gated, whole-heart metabolic volumes. Each of the developments described in this thesis is intended to advance cardiac hyperpolarized 13C metabolic imaging towards a routine, clinical exam which can be used for prognosis and treatment optimization in patients with cardiovascular disease. The major technical development is a new interleaved-frequency, time-resolved MRI pulse sequence that can provide robust and reliable measurements of cardiac metabolic signals. The technique was applied to several realistic pre-clinical models of cardiac disease and the work presented will hopefully lead towards significant improvement in the management of patients with heart failure.

Heart failure is a complex clinical syndrome in which the heart cannot pump sufficient blood and nutrients to the organs in the body. Increasingly, alterations in cardiac energetics are being implicated as playing an important role in the pathogenesis of heart failure. An understanding of specific metabolic switches which occur during the development of heart failure in patients would be greatly beneficial as a new diagnostic method and for the development of new therapies for patients with failing hearts. This thesis deals with the non-invasive assessment of metabolism in the heart. New magnetic resonance imaging (MRI) methods for metabolic characterization of the heart using hyperpolarized carbon-13 MRI are presented. Spatially resolved images of hyperpolarized 13C substrates and their downstream products can provide insight into real-time metabolic processes occurring in vivo, within minutes of injection of a pre-polarized 13C-labeled substrate. Conventional 3D spectroscopic acquisitions require in excess of 100 excitations, making it challenging to acquire full cardiac and respiratory-gated, whole-heart metabolic volumes. Each of the developments described in this thesis is intended to advance cardiac hyperpolarized 13C metabolic imaging towards a routine, clinical exam which can be used for prognosis and treatment optimization in patients with cardiovascular disease. The major technical development is a new interleaved-frequency, time-resolved MRI pulse sequence that can provide robust and reliable measurements of cardiac metabolic signals. The technique was applied to several realistic pre-clinical models of cardiac disease and the work presented will hopefully lead towards significant improvement in the management of patients with heart failure.

In recent years, the use of magnetic resonance technology has grown with advances in hardware, delivering accessible and small-size equipment and devices that open a range of new applications. Innovation in this field requires versatility and flexibility of both hardware and software. Despite the technological advances in the magnetic resonance hardware, the software still the most notable problem currently. This stagnation, delays progress that could reduce production costs and deliver faster development. Researchers in this field are unsatisfied with currently available options. In this panorama, we seek the enhancement of our specific framework for programming magnetic resonance systems, employing concepts from the areas of computing, engineering, and physics. This setup allows the software to merge different perceptions, causing it to be flexible and robust. We converged to Python and object-oriented programming to offer the Python Magnetic Resonance framework - PyMR. The PyMR includes graphical interfaces from templates that can be filled with data, requiring no programming. Our framework comprises other programming tools such as our plugin for the Spyder IDE, which creates the perfect environment to create systems and the pulse sequences. Also, a user-friendly magnetic resonance simulator MR SPRINT, derived from the PyMR structure, addresses educational use, exposing the whole experiment construction, setup, and visualization. Including, PyMR has been contributing to new challenging magnetic resonance systems, introducing modern concepts to change the actual scenario the researchers are facing when developing new magnetic resonance systems. / Nos últimos anos, o uso da tecnologia de ressonância magnética cresceu com os avanços em hardware, fornecendo equipamentos e dispositivos acessíveis e de pequeno porte que abrem uma série de novas aplicações. Inovações neste campo requerem versatilidade e flexibilidade de hardware e software. Apesar dos avanços tecnológicos no hardware de ressonância magnética, o software ainda é um dos maiores problemas atualmente. Essa estagnação atrasa o progresso que poderia reduzir os custos de produção e proporcionar um desenvolvimento mais rápido. Além disso, pesquisadores neste campo estão insatisfeitos com as opções atualmente disponíveis. Com este panorama, buscamos o aprimoramento de nosso framework para programação de sistemas de ressonância magnética, empregando conceitos das áreas de computação, engenharia e física. Essa configuração permite que o software mescle visões de diferentes meios, fazendo com que a estrutura seja flexível e robusta. Nós convergimos, então, para a linguagem Python e programação orientada a objetos para oferecer o framework Python Magnetic Resonance - PyMR. O PyMR inclui interfaces gráficas a partir de modelos que podem ser preenchidos com dados, sem a necessidade de programação. Nossa estrutura compreende outras ferramentas de programação, como o nosso plugin para o Spyder IDE, que cria o ambiente perfeito para criar novos sistemas e sequências de pulsos. Além disso, um simulador de ressonância magnética de fácil utilização, MR SPRINT, derivado da estrutura PyMR, aborda o uso educacional, expondo toda a construção, configuração e visualização do experimento. O PyMR vem contribuindo para novos e desafiadores sistemas de ressonância magnética, introduzindo conceitos modernos para mudar o cenário atual que os pesquisadores estão enfrentando.

Orientador: Claudio Francisco Tormena / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-14T14:30:02Z (GMT). No. of bitstreams: 1 Santos_FranciscoPaulodos_D.pdf: 15350887 bytes, checksum: 67e192401b6f5d14d6d2568ea89baff1 (MD5) Previous issue date: 2009 / Resumo: A tese está estruturada da seguinte forma. Primeiro uma parte introdutória relatando o efeito das interações hiperconjugativas na constante de acoplamento JXY e uma discussao sobre a as principais metodologias para a determinação de constantes de acoplamento a JXY a longa distância. Nesta primeira parte o leitor e introduzido nos tópicos básicos desta tese. Seguindo o corpo da tese contém os resultados e discussão. Primeiro apresentamos as metodologias para determinação das constantes de acoplamento JCH com enfase para o experimento de HSQMBC e para os experimentos de estado de spin seletivo (HSQC-TOCSY-IPAP e HSQC-TOCSY-IPAP-triplamente editado). Posteriormente apresentamos uma racionalização para a diferença entre os acoplamentos JC4H1 e JC1H4 da 3-exo-2-norbornanona (X = Cl, Br, SCH3). Mostramos que ambos os acoplamentos JC1H e JC4H14 deveriam apresentar uma redução de seus valores, devido as interações hiperconjugativas sC1-C7p*C2=O e sC1-C7s*C2=O que retiram densidade eletrônica do caminho a três ligações.Entretanto, observamos que a existência de uma terceira interação sC3-C4s*C2-O recupera parte da densidade eletrônica do acoplamento JC4H1 através de um caminho adicional a quatro ligações fazendo com que o acoplamento JC4H1 seja maior. Este caminho a quatro ligações é similar ao observado em sistemas homoalílicos, sendo que a principal diferença é a natureza do orbital antiligante, que para nossos sistemas é um orbital do tipo s, enquanto para os homoalílicos é do tipo p. / Abstract: In the introduction, it is presented a discussion about the effect of hyperconjugative interactions on coupling constants and a discussion about some methodologies for the measurement of long range heteronuclear coupling constants. JCH, with special emphasis on HSQMBC experiments and the spin state selective methodologies (HSQC-TOCSY-IPAP and HSQC-TOCSY-IPAP-triple editing). After that, a rationalization of the known difference between the JC4H1 and JC1H4 coupling constant transmitted mainly through the 7-bridge in norbornanone is presented in terms of the effects of hyperconjugative interactions involving the carbonyl group. Theoretical and experimental JC4H couplings were carried out for 3-endo- and 3-exo-X-2-norbornanone (X = Cl, Br, SCH3) and for exo- and endo-2- norbornanes derivatives. The hyperconjugative interactions were studied with the Natural Bond Orbital (NBO) analyses. It was observed that interactions involving the carbonyl p*C2=O and s*C2=O antibonding orbitals produce a decrease of threebond contribution for o both JC4H1 and JC1H4 couplings.However, the latter antibonding orbital also undergoes a strong sC3-C4s*C2=O interaction, which defines an additional coupling pathway for JC4H1 but not for JC1H4 .This pathway is similar to that known for homoallylic couplings, being the only difference the nature of the intermediate antibonding orbital, i.e. for JC4H1 is of s-type, while in homoallylic couplings is of p-type. / Doutorado / Quimica Organica / Doutor em Ciências

Magnetic Resonance Elastography is a method of imaging the elasticity of soft tissues through measurement of small motions induced into a sample. It shows great promise in the detection of a wide variety of pathologies, especially tumours. An imaging protocol was developed to acquire MR elastography data for use in a clinical setting. A 3D gradient echo sequence was modified to allow for the detection of harmonic motion and tested on silicone phantoms and ex-vivo muscle and brain samples. The time for acquiring a high resolution, quantitative dataset of 3D motions was about 45 minutes. Our imaging method included motion encoding along all three coordinate axes and at several time points along the motion cycle. This time could be easily be reduced by more than half for future clinical use, while still retaining full quantitative data. A modified EPI sequence shows promise for even faster acquisition. The ability to detect the mechanical anisotropy of brain and muscle tissue in ex-vivo samples was also investigated. Initial results from the muscle data indicate a change in shear wavelength is observed for actuation along orthogonal axes. This is a strong indicator of anisotropy detection. Further work needs to be done to improve results from the brain sample as preliminary results are inconclusive.

Diffusion magnetic resonance imaging (dMRI) has made a significant breakthrough in neurological disorders and brain research thanks to its exquisite sensitivity to tissue cytoarchitecture. However, as the water diffusion process in neuronal tissues is a complex biophysical phenomena at molecular scale, it is difficult to infer tissue microscopic characteristics on a voxel scale from dMRI data. The major methodological contribution of this thesis is the development of an integrated and generic Monte Carlo simulation framework, 'Diffusion Microscopist Simulator' (DMS), which has the capacity to create 3D biological tissue models of various shapes and properties, as well as to synthesize dMRI data for a large variety of MRI methods, pulse sequence design and parameters. DMS aims at bridging the gap between the elementary diffusion processes occurring at a micrometric scale and the resulting diffusion signal measured at millimetric scale, providing better insights into the features observed in dMRI, as well as offering ground-truth information for optimization and validation of dMRI acquisition protocols for different applications.We have verified the performance and validity of DMS through various benchmark experiments, and applied to address particular research topics in dMRI. Based on DMS, there are two major application contributions in this thesis. First, we use DMS to investigate the impact of finite diffusion gradient pulse duration (delta) on fibre orientation estimation in dMRI. We propose that current practice of using long delta, which is enforced by the hardware limitation of clinical MRI scanners, is actually beneficial for mapping fibre orientations, even though it violates the underlying assumption made in q-space theory. Second, we employ DMS to investigate the feasibility of estimating axon radius using a clinical MRI system. The results suggest that the algorithm for mapping the direct microstructures is applicable to dMRI data acquired from standard MRI scanners.

Magnetic Resonance Elastography is a method of imaging the elasticity of soft tissues through measurement of small motions induced into a sample. It shows great promise in the detection of a wide variety of pathologies, especially tumours. An imaging protocol was developed to acquire MR elastography data for use in a clinical setting. A 3D gradient echo sequence was modified to allow for the detection of harmonic motion and tested on silicone phantoms and ex-vivo muscle and brain samples. The time for acquiring a high resolution, quantitative dataset of 3D motions was about 45 minutes. Our imaging method included motion encoding along all three coordinate axes and at several time points along the motion cycle. This time could be easily be reduced by more than half for future clinical use, while still retaining full quantitative data. A modified EPI sequence shows promise for even faster acquisition. The ability to detect the mechanical anisotropy of brain and muscle tissue in ex-vivo samples was also investigated. Initial results from the muscle data indicate a change in shear wavelength is observed for actuation along orthogonal axes. This is a strong indicator of anisotropy detection. Further work needs to be done to improve results from the brain sample as preliminary results are inconclusive.

T1 mapping of myocardial tissue is important for diagnostics of myocardial fibrosis. Cardiac magnetic resonance imaging of small animals is challenging due to high heart and respiratory rates. Pulse sequences for T1 mapping are proposed in this thesis based on inversion recovery FLASH and Intragate FLASH. The sequence IR FLASH was compared to the reference sequence RARE on a static phantom. Both sequences were applied for measuring the myocardium of a rat. For T1 quantification a software in Matlab was developed. Using this software, T1 maps of rat myocardium were calculated.