PURPOSE: To assess the variability of incidental magnetization transfer effect (MT) by the number of slices and the magnetic field strength. METHODS: Various magnetic resonance images (MRI) were obtained with a phantom containing a series of solutions of gadolinium (Gd) and sucrose in distilled water, agarose gel and two vials with olive oil and distilled water. A diffusion weighted image (DWI) sequence was acquired to determine diffusion coefficient for each component of the phantom. Several inversion recovery (IR) sequences having different TI values were run for single-slice and used to calculate T1 relaxation time with maximum precision and minimizing magnetization transfer effect. The T1 relaxation value resulting from processing IR sequences was used as reference value. The mixed-TSE sequences were used to calculate T1, T2 and PD values and to assess MT effect for single-slice as for multi-slice acquisition. All the DICOM MR images were processed using various algorithms programmed in Mathcad (version 2001i, PTC Needham, MA) by Dr. Hernan Jara. According with the potential of each sequences the programs generated the qMRI maps and values of T1, T2, PD were obtained for all the components of the phantom. Values resulted from Mathcad calculation were used for analysis. All the acquisitions, calculations and measurements were performed for 1.5T and 3T field strength.

Neste trabalho analisou-se por ressonância magnética nuclear em baixa (RMN-BR) e em alta resolução (RMN-AR), compostos de coordenação contendo íons paramagnéticos em solução. Demonstrou-se que estas são importantes ferramentas para o estudo destas espécies em meio aquoso, visando aplicações tanto em química analítica quanto em química inorgânica e bioinorgânica. Os estudos iniciais foram realizados com o ligante EDTA (Y4-), clássico agente quelante, e seus complexos com os íons Cu2+, Fe3+ e Mn2+. Os resultados demonstraram que a RMN-BR (20 MHz para o 1H) torna-se uma eficiente alternativa à espectrofotometria, principalmente para o estudo de complexos que não absorvem radiação no visível, como por exemplo, o quelato [Mn-Y]2-. A relaxometria por RMN-BR também foi usada para estudar soluções de quitosana (Chi) e seus complexos com os mesmos íons paramagnéticos previamente abordados para o EDTA. Os resultados demonstraram a eficiência da relaxometria tanto para os estudos de agregação polimérica em função do pH quanto para os estudos de complexação.<a name=\"_Hlk488851348\"> Foram também abordados complexos de sorbitol com íons Cu2+ tanto por relaxometria quanto por RMN-AR (600 MHz para o 1H). Neste caso, os resultados apresentaram uma alta complementariedade, permitindo inferir tanto acerca da troca de ligantes em solução e do pH ótimo para a complexação, quanto do surgimento de espécies macromoleculares com baixos coeficientes de autodifusão (D &asymp; 1,58 x10-10 mm2.s-1) em meio alcalino (pH &asymp; 12). Além do mais, foram avaliados novos complexos de Gd3+ com relevância biológica (agentes de contrastes), derivados do ligante AAZTA (6-amino-6-metilperhidro-1,4-diazepina). Os resultados demonstraram que as relaxividades paramagnéticas (r1p) foram de 7,44 mM-1.s-1 e 9,41 mM-1.s-1 para os derivados funcionalizados lateralmente com os ácidos propanoico e pentanoico, respectivamente, em comparação ao ligante precursor, 7,10 mM-1.s-1. Os estudos relaxométricos in vitro mostraram que estes novos derivados são menos susceptíveis à transmetalação com íons endógenos (Zn2+ e Ca2+), quando comparado ao AAZTA, possibilitando projetar o seu uso como agentes de contraste em tomografia por ressonância magnética (MRI). Aplicações relaxométricas in vivo foram realizadas utilizando o derivado contendo o ácido pentanoico conjugado ao peptídeo FibPep, apto a se ligar à proteína fibrina (presente em células tumorais). Os resultados demonstraram uma alta habilidade deste complexo para o assinalamento precoce e inequívoco do câncer de próstata (linhagem tumoral PC-3) em camundongos. / Low-resolution (LR) and high-resolution (HR) nuclear magnetic resonance (NMR) was used in this work for study coordination compounds containing paramagnetic ions in solution. It was demonstrated that these spectroscopies are important tools for the study of these species in aqueous medium, aiming applications in both, analytical chemistry and inorganic and bioinorganic chemistry. The initial studies were conducted using the EDTA (Y4-) ligand, classical complexant, and its chelate with the paramagnetic ions, among them Cu2+, Fe3+ and Mn2+. The results demonstrated that LR-NMR (20 MHz to 1H) becomes an efficient alternative to spectrophotometry, mainly for the study of complexes that do not absorb visible radiation, such as [Mn-Y]2- chelate. The LR-NMR relaxometry was also used to study chitosan (Chi) solutions and their complexes with the same paramagnetic ions previously discussed for EDTA. The results demonstrated the efficiency of the relaxometry for studies involving complexation and polymer aggregation as a function of the pH. Complexes of sorbitol with cupric ions were also addressed by relaxometry and HR-NMR (600 MHz to 1H). In this case, the results showed a high complementarity, allowing to infer about the ligand exchange and the optimum pH for the complexation reaction occurs. Besides, this study showed the appearance of species with low auto diffusion coefficients (D &asymp; 1.58 x10-10 mm2.s-1) in alkaline mediums (pH &asymp; 12), as consequence of the macromolecular character of this complex in this environment. In addition, new biologically relevant Gd3+ complexes (contrast agents) derived from AAZTA (6-amino-6-methylperhydro-1,4-diazepine) ligand were evaluated. The results demonstrated that the paramagnetic relaxivities (r1p) were 7.44 mM-1.s-1 and 9.41 mM-1.s-1 for derivatives laterally functionalized with propanoic and pentanoic acids, respectively, in comparison to precursor ligand, 7.10 mM-1.s-1. In vitro relaxometric studies demonstrated that these new derivatives are less susceptible to transmetallation reactions towards to endogenous ions (Zn2+ and Ca2+), in comparison to AAZTA (precursor ligand), becoming possible to design their use as contrast agents in magnetic resonance imaging (MRI) tomography applications. In vivo studies were conducted using the pentanoic acid derivative conjugated to FibPep peptide, able to bind to fibrin protein (present in tumor cells). The results for this study demonstrated a high ability of this complex for the early and unequivocal signaling for prostate cancer (PC-3 tumoral cell line) in mice.

Neste trabalho analisou-se por ressonância magnética nuclear em baixa (RMN-BR) e em alta resolução (RMN-AR), compostos de coordenação contendo íons paramagnéticos em solução. Demonstrou-se que estas são importantes ferramentas para o estudo destas espécies em meio aquoso, visando aplicações tanto em química analítica quanto em química inorgânica e bioinorgânica. Os estudos iniciais foram realizados com o ligante EDTA (Y4-), clássico agente quelante, e seus complexos com os íons Cu2+, Fe3+ e Mn2+. Os resultados demonstraram que a RMN-BR (20 MHz para o 1H) torna-se uma eficiente alternativa à espectrofotometria, principalmente para o estudo de complexos que não absorvem radiação no visível, como por exemplo, o quelato [Mn-Y]2-. A relaxometria por RMN-BR também foi usada para estudar soluções de quitosana (Chi) e seus complexos com os mesmos íons paramagnéticos previamente abordados para o EDTA. Os resultados demonstraram a eficiência da relaxometria tanto para os estudos de agregação polimérica em função do pH quanto para os estudos de complexação.<a name=\"_Hlk488851348\"> Foram também abordados complexos de sorbitol com íons Cu2+ tanto por relaxometria quanto por RMN-AR (600 MHz para o 1H). Neste caso, os resultados apresentaram uma alta complementariedade, permitindo inferir tanto acerca da troca de ligantes em solução e do pH ótimo para a complexação, quanto do surgimento de espécies macromoleculares com baixos coeficientes de autodifusão (D &asymp; 1,58 x10-10 mm2.s-1) em meio alcalino (pH &asymp; 12). Além do mais, foram avaliados novos complexos de Gd3+ com relevância biológica (agentes de contrastes), derivados do ligante AAZTA (6-amino-6-metilperhidro-1,4-diazepina). Os resultados demonstraram que as relaxividades paramagnéticas (r1p) foram de 7,44 mM-1.s-1 e 9,41 mM-1.s-1 para os derivados funcionalizados lateralmente com os ácidos propanoico e pentanoico, respectivamente, em comparação ao ligante precursor, 7,10 mM-1.s-1. Os estudos relaxométricos in vitro mostraram que estes novos derivados são menos susceptíveis à transmetalação com íons endógenos (Zn2+ e Ca2+), quando comparado ao AAZTA, possibilitando projetar o seu uso como agentes de contraste em tomografia por ressonância magnética (MRI). Aplicações relaxométricas in vivo foram realizadas utilizando o derivado contendo o ácido pentanoico conjugado ao peptídeo FibPep, apto a se ligar à proteína fibrina (presente em células tumorais). Os resultados demonstraram uma alta habilidade deste complexo para o assinalamento precoce e inequívoco do câncer de próstata (linhagem tumoral PC-3) em camundongos. / Low-resolution (LR) and high-resolution (HR) nuclear magnetic resonance (NMR) was used in this work for study coordination compounds containing paramagnetic ions in solution. It was demonstrated that these spectroscopies are important tools for the study of these species in aqueous medium, aiming applications in both, analytical chemistry and inorganic and bioinorganic chemistry. The initial studies were conducted using the EDTA (Y4-) ligand, classical complexant, and its chelate with the paramagnetic ions, among them Cu2+, Fe3+ and Mn2+. The results demonstrated that LR-NMR (20 MHz to 1H) becomes an efficient alternative to spectrophotometry, mainly for the study of complexes that do not absorb visible radiation, such as [Mn-Y]2- chelate. The LR-NMR relaxometry was also used to study chitosan (Chi) solutions and their complexes with the same paramagnetic ions previously discussed for EDTA. The results demonstrated the efficiency of the relaxometry for studies involving complexation and polymer aggregation as a function of the pH. Complexes of sorbitol with cupric ions were also addressed by relaxometry and HR-NMR (600 MHz to 1H). In this case, the results showed a high complementarity, allowing to infer about the ligand exchange and the optimum pH for the complexation reaction occurs. Besides, this study showed the appearance of species with low auto diffusion coefficients (D &asymp; 1.58 x10-10 mm2.s-1) in alkaline mediums (pH &asymp; 12), as consequence of the macromolecular character of this complex in this environment. In addition, new biologically relevant Gd3+ complexes (contrast agents) derived from AAZTA (6-amino-6-methylperhydro-1,4-diazepine) ligand were evaluated. The results demonstrated that the paramagnetic relaxivities (r1p) were 7.44 mM-1.s-1 and 9.41 mM-1.s-1 for derivatives laterally functionalized with propanoic and pentanoic acids, respectively, in comparison to precursor ligand, 7.10 mM-1.s-1. In vitro relaxometric studies demonstrated that these new derivatives are less susceptible to transmetallation reactions towards to endogenous ions (Zn2+ and Ca2+), in comparison to AAZTA (precursor ligand), becoming possible to design their use as contrast agents in magnetic resonance imaging (MRI) tomography applications. In vivo studies were conducted using the pentanoic acid derivative conjugated to FibPep peptide, able to bind to fibrin protein (present in tumor cells). The results for this study demonstrated a high ability of this complex for the early and unequivocal signaling for prostate cancer (PC-3 tumoral cell line) in mice.

As técnicas de ressonância magnética nuclear (RM), por não serem invasivas ou destrutivas, apresentam um papel importante em diversas áreas do conhecimento como, por exemplo, medicina, química, física, setor rural, setor petrolífero, etc. Entretanto os custos de aquisição, manutenção e atualização dos equipamentos comerciais são muito altos e países em desenvolvimento, como é o caso do Brasil, sofrem com os impactos em função deste fator, principalmente nos setores ligados à pesquisa, em especial, nas áreas de concepção de novos métodos de RM. Além disso, o cenário nacional de desenvolvimento tecnológico desta área é escasso e os equipamentos comerciais fornecidos pelas empresas nem sempre oferecem a flexibilidade desejada. Baseado no uso de tecnologias inovadoras, como é o caso dos hardwares reconfiguráveis e uso de linguagem, compilador, bibliotecas e editores próprios para desenvolvimento de métodos de sequência de pulsos de RM, o Centro de Imagens e Espectroscopia in vivo por Ressonância Magnética (CIERMag) propõe uma solução alternativa através do desenvolvimento de um espectrômetro completamente digital de RM, flexível o suficiente para operar como um tomógrafo. O objetivo deste trabalho é idealizar e desenvolver a camada de software responsável pela aquisição, organização, visualização e armazenamento dos dados provenientes do espectrômetro através do subsistema ToRM Console, levando em consideração a flexibilidade proposta. Além disso, um arcabouço de ferramentas para automatização de pós-processamento, o ToRM Processing API, foi desenvolvido. Ambos os sistemas foram implementados em linguagem Python, com auxílio das principais bibliotecas de propósito científico (Numpy, Scipy, Matplotlib, etc). A realização de um experimento para estudo do comportamento do tempo de relaxação transversal de soluções de sulfato de cobre em função da variação da concentração é mostrada através do uso do método Carr-Purcell-Meiboom-Gill (CPMG). Outras aplicações do espectrômetro são mostradas através da obtenção de dados gerados por meio de sintetizadores de sinais acoplados ao espectrômetro. Os resultados mostram que o espectrômetro atualmente pode operar como um relaxômetro de RM de fácil operação. Os sistemas desenvolvidos neste trabalho mostram-se suficientemente flexíveis e preparados para operação em experimentos de Imagens e Espectroscopia de Alta Resolução, que são futuras etapas de desenvolvimento no CIERMag, tendo em vista as ferramentas desenvolvidas e testadas através do uso de dados sintetizados. / The Nuclear Magnetic Resonance (NMR) techniques, which are neither invasive nor destructive, play an important role on several areas of knowledge, such as Medicine, Chemistry, Physics, Agriculture, Oil industry, among others. However, the costs associated with acquisition, maintenance and upgrade are very high, which have impacted on developing countries, as Brazil. Furthermore, the national scenario of technological development in this area is scarce and the commercial equipment provided by the companies does not always offer the desired flexibility. Based on the use of innovative technologies, which is the case of reconfigurable hardware and the use of proprietary language, compiler, libraries and editors for the development of NMR sequence pulses methods, the Magnetic Resonance Imaging and in vivo Spectroscopy Center (CIERMag) have proposed an alternative solution through the development of a completely digital NMR spectrometer, flexible enough to operate as an MRI Scanner. This dissertation reports the design and development of a software layer responsible for the acquisition, organization, visualization and storage of the data provided by the spectrometer through the ToRM Console subsystem, taking into account the proposed flexibility. A framework for post-processing automation, the ToRM Processing API, is also described. Both systems were developed in Python programming language, with the help of the main scientific purpose libraries (Numpy, Scipy, Matplotlib, etc.). Carr-Purcell-Meiboom-Gill (CPMG) method was used for the evaluation of the transverse relaxation time dependency on variable concentrations of copper sulfate solution. Other spectrometer applications are shown through the acquisition of synthesized data from simulation devices coupled to the spectrometer. The results show that the spectrometer can currently operate as an easy-to-use NMR Relaxometer. The systems described in the present work proved to be sufficiently flexible and prepared for the operation as MRI Scanners or Analytical Spectrometers, which are the future stages of development at CIERMag, considering the tools developed and tested through the use of synthesized data.

As técnicas de ressonância magnética nuclear (RM), por não serem invasivas ou destrutivas, apresentam um papel importante em diversas áreas do conhecimento como, por exemplo, medicina, química, física, setor rural, setor petrolífero, etc. Entretanto os custos de aquisição, manutenção e atualização dos equipamentos comerciais são muito altos e países em desenvolvimento, como é o caso do Brasil, sofrem com os impactos em função deste fator, principalmente nos setores ligados à pesquisa, em especial, nas áreas de concepção de novos métodos de RM. Além disso, o cenário nacional de desenvolvimento tecnológico desta área é escasso e os equipamentos comerciais fornecidos pelas empresas nem sempre oferecem a flexibilidade desejada. Baseado no uso de tecnologias inovadoras, como é o caso dos hardwares reconfiguráveis e uso de linguagem, compilador, bibliotecas e editores próprios para desenvolvimento de métodos de sequência de pulsos de RM, o Centro de Imagens e Espectroscopia in vivo por Ressonância Magnética (CIERMag) propõe uma solução alternativa através do desenvolvimento de um espectrômetro completamente digital de RM, flexível o suficiente para operar como um tomógrafo. O objetivo deste trabalho é idealizar e desenvolver a camada de software responsável pela aquisição, organização, visualização e armazenamento dos dados provenientes do espectrômetro através do subsistema ToRM Console, levando em consideração a flexibilidade proposta. Além disso, um arcabouço de ferramentas para automatização de pós-processamento, o ToRM Processing API, foi desenvolvido. Ambos os sistemas foram implementados em linguagem Python, com auxílio das principais bibliotecas de propósito científico (Numpy, Scipy, Matplotlib, etc). A realização de um experimento para estudo do comportamento do tempo de relaxação transversal de soluções de sulfato de cobre em função da variação da concentração é mostrada através do uso do método Carr-Purcell-Meiboom-Gill (CPMG). Outras aplicações do espectrômetro são mostradas através da obtenção de dados gerados por meio de sintetizadores de sinais acoplados ao espectrômetro. Os resultados mostram que o espectrômetro atualmente pode operar como um relaxômetro de RM de fácil operação. Os sistemas desenvolvidos neste trabalho mostram-se suficientemente flexíveis e preparados para operação em experimentos de Imagens e Espectroscopia de Alta Resolução, que são futuras etapas de desenvolvimento no CIERMag, tendo em vista as ferramentas desenvolvidas e testadas através do uso de dados sintetizados. / The Nuclear Magnetic Resonance (NMR) techniques, which are neither invasive nor destructive, play an important role on several areas of knowledge, such as Medicine, Chemistry, Physics, Agriculture, Oil industry, among others. However, the costs associated with acquisition, maintenance and upgrade are very high, which have impacted on developing countries, as Brazil. Furthermore, the national scenario of technological development in this area is scarce and the commercial equipment provided by the companies does not always offer the desired flexibility. Based on the use of innovative technologies, which is the case of reconfigurable hardware and the use of proprietary language, compiler, libraries and editors for the development of NMR sequence pulses methods, the Magnetic Resonance Imaging and in vivo Spectroscopy Center (CIERMag) have proposed an alternative solution through the development of a completely digital NMR spectrometer, flexible enough to operate as an MRI Scanner. This dissertation reports the design and development of a software layer responsible for the acquisition, organization, visualization and storage of the data provided by the spectrometer through the ToRM Console subsystem, taking into account the proposed flexibility. A framework for post-processing automation, the ToRM Processing API, is also described. Both systems were developed in Python programming language, with the help of the main scientific purpose libraries (Numpy, Scipy, Matplotlib, etc.). Carr-Purcell-Meiboom-Gill (CPMG) method was used for the evaluation of the transverse relaxation time dependency on variable concentrations of copper sulfate solution. Other spectrometer applications are shown through the acquisition of synthesized data from simulation devices coupled to the spectrometer. The results show that the spectrometer can currently operate as an easy-to-use NMR Relaxometer. The systems described in the present work proved to be sufficiently flexible and prepared for the operation as MRI Scanners or Analytical Spectrometers, which are the future stages of development at CIERMag, considering the tools developed and tested through the use of synthesized data.

The work presented in this dissertation involves the development of parametric magnetic resonance imaging (MRI) techniques that can be used in a clinical set up. In the first chapter an introduction of basic magnetic resonance physics is given. The introduction covers the source to tissue magnetization, the origin of the detectable signal, the relaxation mechanisms, and the imaging principles. In the second chapter T₂ estimation - the main parametric MRI technique addressed in this work - is introduced and the problem associated with T₂ estimation from highly undersampled fast spin-echo (FSE) data is presented. In Chapter 3, a novel model-based algorithm with linearization by principal component analysis (REPCOM) is described. Based on simulations, physical phantom and in vivo data, the proposed algorithm is shown to produce accurate and stable T₂ estimates. In Chapter 4, the concept of indirect echoes associated with the acquisition of FSE data is introduced. Indirect echo correction using the extended phase graph approach is then studied for standard sampled data. A novel reconstruction algorithm (SERENADE) is presented for the reconstruction of decay curves with indirect echoes from highly undersampled data. The technique is evaluated using simulations, physical phantom and in vivo data; decay curves with indirect echoes are shown to be accurately recovered by this technique. Chapter 5 is dedicated to correcting the partial volume effect (PVE) in T₂ estimation. For the case of small lesions within a background tissue, PVE affects T₂ estimation which in turn affects lesion classification. A novel joint fitting algorithm is proposed and compared to conventional fitting algorithms using fully sampled spin-echo (SE) images. It is shown that the proposed algorithm is more accurate, robust, and insensitive to region of interest drawing than the conventional fitting algorithms. Because the acquisition of fully sampled SE images is long, the technique is combined with a thick refocusing slice approach in order to be able to use undersampled FSE data and reduce the acquisition time to a breath hold (~ 20 s). The final chapter summarizes the results presented in the dissertations and discusses areas for future work.

Dans cette thèse, nous avons proposé deux modèles multi-compartiments en IRM de relaxométrie T2 (MCT2) fournissant des informations sur la microstructure des tissus cérébraux. Trois compartiments de relaxométrie T2 ont été considérés dans chaque voxel représentant des tissus avec des temps de relaxation T2 courts, T2 moyens et T2 élevés. La complexité associée à l'estimation des paramètres de tels modèles paramétriques a ensuite été explorée. Le premier modèle MCT2 que nous avons proposé a estimé la représentation fractionnelle de compartiments T2 prédéfinis. Dans le second modèle, les représentations fractionnaires et le paramètre de relaxation moyenne ont été estimés pour le compartiment T2 moyen. Dans les deux modèles, le choix de l'approche était justifié par une analyse de la fonction de coût et un cadre d’estimation a été proposé. Le modèle MCT2 a été utilisé pour deux applications. Dans la première application, l’évolution des biomarqueurs de MCT2 a été étudiée dans les lésions de sclérose en plaques (SEP) présentant une prise de contraste gadolinium (Gd) ou non chez 10 patients présentant un syndrome cliniquement isolé. La seconde application a démontré le potentiel de combinaison des biomarqueurs MCT2 avec les informations de microstructure dérivées de l'IRM de diffusion pour identifier les régions présentant une prise de contraste Gd dans les lésions de SEP. Les résultats montrent que les biomarqueurs MCT2 proposés peuvent constituer des outils efficaces pour étudier l’état et l’évolution de la microstructure tissulaire dans le cerveau. La combinaison des biomarqueurs MCT2 avec les informations de microstructure dMRI nous a permis de progresser vers la résolution d’un problème critique et délicat consistant à limiter l'utilisation de gadolinium dans la détection de régions de lésion améliorantes dans les lésions de SEP. / In this thesis, we propose two multi-compartment T2 relaxometry (MCT2) models which provide information on brain tissue microstructure. Three T2 relaxometry compartments were considered in each voxel representing tissues with short T2, medium T2 and high T2 relaxation times. The complexity associated with the estimation of the parameters for such parametric models has then been explored. The first MCT2 model we propose computes the fractional representation of pre-defined T2 pools. In the next MCT2 model the fractional representations as well as T2 pool parameter were estimated for the medium T2 compartment. For both models the choice of approach was justified using a cost function analysis and a dedicated estimation framework was proposed.Our MCT2 model was used for two applications. In the first application the evolution of MCT2 biomarkers was studied in gadolinium (Gd) enhancing and nonenhancing regions of multiple sclerosis (MS) lesions in 10 patients with clinically isolated syndrome. The potential of combining the MCT2 biomarkers with diffusion MRI (dMRI) derived microstructure information to identify Gd enhancing regions in MS lesions was then demonstrated in the second application. The results show that the proposed MCT2 biomarkers can be effective tools to study the condition and evolution of tissue microstructures in the brain. Combining the MCT2 biomarkers with dMRI microstructure information enabled us to address a critical and challenging problem of limiting the use of gadolinium usage in detecting enhancing lesion regions in MS patients.

A espectroscopia de Ressonância Magnética Nuclear (RMN) em baixo campo tem demonstrado ser um método rápido e confiável para se avaliar a qualidade da carne. A predição desta, especialmente a carne de porco, tem sido avaliada usando o tempo de relaxação transversal (T2). As medidas foram feitas com a seqüência de pulsos CPMG (Carr-Purcell-Meibom-Gill) que correlaciona os parâmetros da qualidade da carne de suínos, tais como, a capacidade de retenção de água (CRA), o pH e perda de água por cocção (PPC), com tempo de relaxação T2. Neste trabalho, analisou-se a qualidade da carne bovina pela seqüência de pulsos CPMG, que é dependente do tempo relaxação transversal (T2), e pela técnica de precessão livre de onda continua (CWFP), que depende de T2 e da relaxação longitudinal (T1). Foram analisadas amostras do contra-filé do tipo músculo- longissimus lumborum, retiradas da região da 12ª e da 6ª costela de bovinos, de três grupos genéticos de bovinos; adaptados ou não às condições tropicais, sendo dois deles de 3/4 e um de 9/16 de sangue europeu. Os dados de CPMG foram analisados utilizando-se os processamentos de análise multiexponencial discreta, análise multiexponencial contínua, baseada na transformada inversa de Laplace (ILT) e com métodos quimiométricos como análises de componentes principais (PCA), análises de agrupamentos hierárquicos (HCA) e regressão por mínimos quadrados parciais (PLS). Os dados de CWFP por serem mais complexos do que os do CPMG foram analisados principalmente por métodos quimiométricos. Conclui-se que não há diferença significativa entre o corte realizado na 12ª costela com o da 6ª costela e que a técnica CWFP é mais eficaz na separação entre o sexo e grupo genético dos animais, do que a técnica CPMG / Low resolution Nuclear magnetic resonance spectroscopy (NMR) is shown to be a fast and accurate method for evaluating meat quality. The prediction of meat quality, especially in pork, has been performed using transverse relaxation time (T2). The measurements have been made with CPMG (Carr-Purcell-Meibom-Gill) pulse sequence which correlate the pork quality parameters such as water-holdcapacity (WHC), pH, and cooking loss (CL) with T2. In this work, the beef quality has been analyzed evaluated by transverse relaxation time (T2) measured by CPMG pulse sequence and by the T2, and, longitudinal relaxation time (T1), measured by CWFP (Continuous Wave Free Precession) technique The samples were collected from Longissimus lumborium muscle, from the 12th and 6th ribs region. The animals from three genetic groups, (two were ¾ and one was 9/16 european) were used in the experiments. The CPMG data were processed by multiexponential fitting, inverse Laplace transformation and chemometrics methods such as principal component analysis, hierarchic cluster analysis and partial least square regression. The CPMG data were not able to distinguish between the genetic group sex and the meat cut. The CWFP data analyzed by chemometrics methods show difference between Canchin males and females and between Canchin and Angus males. The results show almost no difference between the samples collected from the 12th and 6th rib.

A capacidade do ferro, presente no corpo humano, em aceitar e doar elétrons o torna essencial para homeostase celular e várias reações biológicas. Contudo, o excesso deste metal no cérebro pode gerar efeitos deletérios através da produção de espécies reativas de oxigênio que causam o estresse oxidativo. Este estresse aparece como possível causa de doenças neurodegenerativas, caracterizadas por um aumento significativo da concentração de ferro em certas regiões do cérebro. Detectar e quantificar a deposição de ferro in vivo no cérebro torna-se de extrema relevância para entender diversas doenças neurodegenerativas. Neste estudo avaliamos a sensibilidade e a especificidade das principais técnicas de Ressonância Magnética in vivo para estimar o conteúdo de ferro depositado no cérebro. Foram estudados um grupo de 16 sujeitos saudáveis e outro de 14 pacientes com doença de Parkinson. Mapas de relaxometria (R2 e R2*) e susceptibilidade (QSM) foram estimados a partir de imagens adquiridas numa maquina de RM de 3.0T. Embora todos os mapas tenham apresentado correlação linear (r2 = 0; 7) com o acumulo de ferro reportado in vitro nas regiões do núcleo da base, apenas os mapas R2 e QSM apresentaram estatisticamente aumento significativo (p<0,05) para certas regiões do cérebro parkinsoniano (substância negra, núcleo rubro e globo pálido). O mapa QSM apresentou maior sensibilidade e especificidade para diferenciar pacientes com a doença quando comparados a sujeitos saudáveis por meio da análise da curva ROC. Concluímos que os mapas de relaxometria e susceptibilidade magnética podem estimar de forma indireta o conteúdo de ferro no cérebro, apesar de apresentarem dependências diferentes com a concentração deste metal. Observamos também que os valores de sususceptibilidade magnética obtidos com imagens de baixa resolução (1,0x1,0x2,0mm) não apresentaram mudanças significativas em relação aos obtidos com imagens de alta resolução (0,5x0,5x2,0mm). Logo, sugerimos a aquisição de imagens com baixa resolução para o processamento do mapa QSM. A analise de múltiplos valores de tempo de relaxação T2 determinou apenas um valor para cada região do núcleo da base para ambos os grupos, este resultado foi aparentemente afetado pela relação sinal ruído. / The capacity of the iron present in the human body to accept and donate electrons makes it essential for cellular homeostasis and various biological reactions. However, an excess of the metal in the brain can produce deleterious effects through the production of reactive oxygen species that cause oxidative stress. This stress can be the possible cause of neurodegenerative diseases which present a significant increase in iron concentration in certain brain regions. To detect and quantify iron deposition in the brain in vivo has high potential for understanding neurodegenerative diseases. In this study we evaluated the sensitivity and specificity of the main Magnetic Resonance technique in vivo to estimate the content of iron deposited in the brain. Were studied a group of 16 controls and 14 patient with Parkinson disease. Relaxometry map (R2 and R2*) and magnetic susceptibility map QSM were estimated by images obtained of scanner of Magnetic Resonance of 3T. Although all maps have presented linear correlation (r2=0.7) with the accumulation of iron reported in vitro regions of basal ganglia, only the R2 and QSM maps showed significant increase (p < 0.05) for certain regions of the parkinsonian brain (substantia nigra, red nucleus, and globus pallidus). The QSM map showed higher sensitivity and especificity for differentiate patients with the disease when compared with controls by the analysis of curve ROC. We conclude that magnetic susceptibility and relaxometry maps may estimate indirect the content of brain iron, although having different dependencies with the concentration of this metal. We also observed that the values of magnetic sususceptibility obtained with low resolution images (1,0 x1, 0x2, 0mm) showed no significant change compared to those obtained with high-resolution images (0,5 x0, 5x2,0mm). So, we suggest the acquisition of images with low resolution to process QSM map. The analysis of multiple relaxation time T2 determined just one value for basal ganglia in both groups, these results were apparently affected by rate noise signal.

Cette thèse est consacrée à la cartographie de la microstructure du cerveau humain par IRM quantitative et de diffusion. L'imagerie quantitative T1/T2 repose sur des séquences dédiées à la cartographie des temps de relaxation T1 et T2. Leurs variations au sein du tissu sont liées aux différents compartiments d'eau issus d'organisations spécifiques à l'échelle cellulaire. Mesurer ces paramètres quantitatifs permet donc de mieux caractériser la microstructure du tissu cérébral. L'IRMd étudie le mouvement brownien des molécules d'eau dans le tissu cérébral dans lequel leur mouvement est contraint par des barrières naturelles, telles que les membranes cellulaires. Ainsi, les informations sur leurs déplacements contenues dans le signal de diffusion permettent de révéler la cytoarchitecture sous-jacente. La combinaison de ces deux modalités donne donc une unique possibilité de mieux sonder la microstructure du tissu cérébral. Ce travail vise à mettre en place la méthodologie permettant d’étudier chez l'homme, in vivo, la microstructure de la matière blanche cérébrale. La première partie inclut l'acquisition d'une base IRM unique de 79 sujets sains (base Archi/CONNECT) incluant des données anatomiques à haute résolution spatiale, des données de relaxométrie, des données de diffusion à haute résolution angulaire, et fonctionnelles. Ces données ont permis dans un premier temps de construire le premier atlas de la connectivité anatomique du sujet sain grâce à la segmentation automatique des grands faisceaux de la substance blanche de tous les sujets. Cet atlas fournit un repère anatomique au sein de la substance blanche pour ensuite étudier pour chaque faisceau les paramètres quantitatifs caractérisant son organisation microstructurelle. L'accent a d’abord été mis sur la construction du premier atlas des profils des temps de relaxation T1/T2 le long des grandes voies de la matière blanche. Ces profils ont ensuite été corrélés avec les profils quantitatifs issus de l'imagerie de diffusion (fraction d'anisotropie, diffusivités radiales et longitudinales, coefficient de diffusion apparent) pour mieux comprendre leurs relations et d'expliquer la variabilité le long des faisceaux et les asymétries interhémisphériques. La deuxième partie de cette thèse fut centrée sur la modélisation du tissu cérébral à l'échelle cellulaire pour extraire des paramètres quantitatifs caractérisant la microstructure, tel que le diamètre et la densité des axones. Une séquence d’IRMd a été développée sur les imageurs 3T et 7T cliniques de NeuroSpin, permettant de jouer n'importe quelle forme de gradients et ainsi de s'inscrire dans une démarche où cette forme résulte d'une optimisation sous l'hypothèse d'un modèle géométrique du tissu et sous contraintes matérielles et temporelles liées aux applications cliniques. Cette séquence a été utilisée pour scanner 14 sujets sains afin de construire le premier atlas du diamètre et de la densité locale des axones. Nous avons également proposé un nouveau modèle géométrique de l'axone, divisant le compartiment axonal, habituellement modélisé par un simple cylindre en deux compartiments: le premier correspondant aux molécules d’eau à diffusivité lente, entourant la membrane de l'axone et le second correspondant aux molécules plus loin des membranes à plus forte diffusivité, moins restreinte. Nous avons mené une étude théorique montrant que sous des conditions cliniques, utiliser ce nouveau modèle pourrait aider à limiter la surestimation des petits axones que l’on observe dans les études actuelles. Pour aller plus loin dans la physiopathologie de l'autisme, nous avons rajouté au protocole d'imagerie à 3T déjà en place la séquence que nous avons développée afin de cartographier le diamètre et la densité des axones et ainsi mieux comprendre les atrophies au sein du corps calleux, initialement observées via des paramètres moins spécifiques tels que la fraction d'anisotropie. D'autres applications cliniques sont à venir. / This thesis is focused on the human brain microstructure mapping using quantitative and diffusion MRI. The T1/T2 quantitative imaging relies on sequences dedicated to the mapping of T1 and T2 relaxation times. Their variations within the tissue are linked to the presence of different water compartments defined by a specific organization of the tissue at the cell scale. Measuring these parameters can help, therefore, to better characterize the brain microstructure. The dMRI, on the other hand, explores the brownian motion of water molecules in the brain tissue, where the water molecules’ movement is constrained by natural barriers, such as cell membranes. Thus, the information on their displacement carried by the dMRI signal gives access to the underlying cytoarchitecture. Combination of these two modalities is, therefore, a promising way to probe the brain tissue microstructure. The main goal of the present thesis is to set up the methodology to study the microstructure of the white matter of the human brain in vivo. The first part includes the acquisition of a unique MRI database of 79 healthy subjects (the Archi/CONNECT), which includes anatomical high resolution data, relaxometry data, diffusion-weighted data at high spatio-angular resolution and functional data. This database has allowed us to build the first atlas of the anatomical connectivity of the healthy brain through the automatic segmentation of the major white matter bundles, providing an appropriate anatomical reference for the white matter to study individually the quantitative parameters along each fascicle, characterizing its microstructure organization. Emphasis was placed on the construction of the first atlas of the T1/T2 profiles along the major white matter pathways. The profiles of the T1 and T2 relaxation times were then correlated to the quantitative profiles computed from the diffusion MRI data (fractional anisotropy, radial and longitudinal diffusivities, apparent diffusion coefficient), in order to better understand their relations and to explain the observed variability along the fascicles and the interhemispheric asymmetries. The second part was focused on the brain tissue modeling at the cell scale to extract the quantitative parameters characterizing the geometry of the cellular membranes, such as the axonal diameter and the axonal density. A diffusion MRI sequence was developed on the 3 Teslas and 7 Teslas Siemens clinical systems of NeuroSpin which is able to apply any kind of gradient waveforms to fall within an approach where the gradient waveform results from an optimization under the hypothesis of a geometrical tissue model, hardware and time constraints induced by clinical applications. This sequence was applied in the study of fourteen healthy subjects in order to build the first quantitative atlas of the axonal diameter and the local axonal density at 7T. We also proposed a new geometrical model to model the axon, dividing the axonal compartment, usually modelled using a simple cylinder, into two compartments: one being near the membranes with low diffusivity and one farer from the membranes, less restricted and with higher diffusivity. We conducted a theoretical study showing that under clinical conditions, this new model allows, in part, to overcome the bias induced by the simple cylindrical model leading to a systematic overestimation of the smallest diameters. Finally, in the aim of going further in the physiopathology of the autism, we added to the current 3T imaging protocol the dMRI sequence developed in the framework of this thesis in order to map the axonal diameter and density. This study is ongoing and should validate shortly the contribution of these new quantitative measures of the microstructure in the comprehension of the atrophies of the corpus callosum, initially observed using less specific diffusion parameters such as the generalized fractional anisotropy. There will be other clinical applications in the future.