This diploma thesis deals with the DCE – MRI method (Dynamic contrast enhanced magnetic resonance imaging). Basic principle of magnetic resonance and pulse sequence is described. The diploma thesis focuses on the DCE method, especially on the description of the processing procedure by this method. Description of selected pharmacokinetic models is the part of this diploma thesis as well. Furthermore, description and realization of batch processing by PerfLab system is presented. For verifying purposes of the batch processing functionality real data were measured using created acquisition protocol, which is also part of the diploma thesis.

Neste trabalho serão discutidas novas ferramentas para a construção de um espectrômetro de Ressonância Magnética (RM) totalmente digital. A motivação parte das dificuldades encontradas pelos pesquisadores no momento de programar um equipamento de RM, incluindo a falta de ferramentas para desenvolvimento de metodologias, as quais não são oferecidas pelos softwares atuais. Em particular tratamos do desenvolvimento de uma biblioteca, a PyMR (Python Magnetic Resonance), de uma API (Application Program Interface) e de um IDE (Integrated Development Environment). Nesta estrutura, a biblioteca PyMR é o front-end para programação e setup dos equipamentos de RM enquanto a API constitui o back-end. O IDE, por sua vez, é uma ferramenta de auxílio especializado para criação e gerenciamento das metodologias e protocolos de RM de forma funcional e amigável. O desenvolvimento baseado no estado-da-arte das tecnologias de Computação e Ressonância Magnética garante a qualidade, robustez, adaptabilidade e ainda assim, a simplicidade para uso dos menos experientes. Para a validação do sistema, além de métricas de software, foi montada uma sequência de pulsos conhecida como CPMG (Carr-Purcell-Meiboom-Gill) executada no espectrômetro local sobre uma amostra de CuSO4 em solução, o qual mostrou valores de T2 compatíveis com os valores esperados. Os resultados do novo sistema mostram sua capacidade de atender as principais exigências dos usuários e desenvolvedores de metodologias de RM, oferecendo um amplo conjunto de ferramentas. Em suma, este projeto provê a estrutura básica e funcional de uma nova forma de se programar e utilizar equipamentos de RM, gerando um poderoso instrumento para a pesquisa na área. / In this study we discuss new tools for the building of a fully digital Magnetic Resonance (MR) spectrometer. The research was motivated by several difficulties experienced by researchers in programming MR machines, which include the lack of tools for the development of methodologies that are not currently offered by companies. In particular, we treat the development of a library, PyMR (Python Magnetic Resonance), an API (Application Program Interface) and an IDE (Integrated Development Environment). In this structure, the PyMR library acts as a front-end for MR equipment programming and setup while the API is a back-end. Finally, the IDE is a user-friendly tool that helps the developer to create and manage methodologies and protocols. The state-of-the-art of Computer Sciences and Magnetic Resonance technologies adopted here has ensured the quality, robustness and adaptability keeping simplicity for non-experienced users. For the validation of the system, besides software metrics, a pulse sequence known as CPMG (Carr-Purcell-Meiboom-Gill) was assembled and performed on an onsite spectrometer, using a solution of CuSO4 as a sample, which exhibited compatible T2 values. The results show that the system can meet the main requirements of both users and developers and offer a large set of tools. This project provides a basic and functional structure of a new way to program and use the MR equipment and a powerful tool for researchers in this area.

L'imagerie par résonance magnétique de diffusion (IRMd) a fait une percée significative dans les troubles neurologiques et les recherches sur le cerveau grâce à son extraordinaire sensibilité à la cytoarchitecture des tissus. Cependant, comme le processus de diffusion de l'eau dans les tissus neuronaux est un phénomène biophysique complexe à l'échelle moléculaire, il est difficile d'en déduire les caractéristiques microscopiques des tissus à l'échelle du voxel, à partir des données d'IRMd. La contribution méthodologique majeure de cette thèse est le développement d'un cadre de simulation de type Monte Carlo intégré et générique, appelé `Diffusion Microscopist Simulator' (DMS), qui permet d'élaborer des modèles de tissus biologiques tridimensionnels aux géométries et propriétés variées et qui permet de synthétiser des données d'IRMd correspondantes pour une grande variété d'IRM, de séquences d'impulsions et de paramètres. L'outil DMS vise à combler le fossé entre les processus de diffusion élémentaires, qui se produisent à une échelle micrométrique, et le signal de diffusion résultant, mesuré à l'échelle millimétrique, qui offre un meilleur aperçu des caractéristiques observées dans l'IRMd, tout en offrant une information vérité terrain pour l'optimisation et la validation des protocoles d'acquisition de l'IRMd pour différentes applications.Nous avons vérifié les performances et la validité du simulateur à travers différents tests, et appliqué cet outil pour aborder des thèmes de recherche particuliers à l'IRMd. Il y a deux contributions majeures dans cette thèse. Tout d'abord, nous avons utilisé l'outil DMS pour étudier l'impact de la durée d'impulsions de gradient de diffusion finies (delta) sur l'estimation de l'orientation des fibres par l'IRMd. Nous avons démontré que la pratique actuelle qui utilise un delta long, imposée par la limitation physique des scanners d'IRM cliniques, est en fait bénéfique pour la cartographie des orientations des fibres, même si elle viole l'hypothèse sous-jacente faite dans la théorie de l'espace q. Deuxièmement, nous avons employé le simulateur pour étudier la possibilité d'estimer le rayon des axones en utilisant un système d'IRM clinique. Les résultats suggèrent que la technique d'inférence de la taille des axones reposant sur un modèle analytique de la réponse IRM d'un axone au processus de diffusion est applicable aux données d'IRMd acquises avec des scanners IRM standards. / 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.

Evolution of vulnerable carotid plaques are crucial reason for cerebral ischemic strokes and identifying them in the early stage can become very important in avoiding the risk of stroke. In order to improve the identification and quantification accuracy of infancy plaques better visualization techniques are needed. Improving the visualization and quantification of neovascularization in carotid plaque using contrast enhanced ultrasound imaging still remains a challenging task. In this thesis work, three optimization techniques are proposed, which showed an improvement in the sensitivity of contrast agents when compared to the conventional clinical settings and insonation strategies. They are as follows:1) Insonation at harmonic specific (2nd harmonic) resonance frequency instead of resonance frequency based on maximum energy absorption provides enhanced nonlinear contribution.2) At high frequency ultrasound imaging, shorter pulse length will provide improved harmonic signal content when compared to longer pulse lengths. Applying this concept to multi- pulse sequencing (Pulse Inversion and Cadence contrast pulse sequencing) resulted in increased magnitude of the remaining harmonic signal after pulse summations.3) Peak negative pressure optimization of Pulse Inversion and Cadence contrast pulse sequencing was showed to further enhance the nonlinear content of the backscattered signal from contrast microbubbles without increasing the safety limits, defined by the mechanical index.The results presented in this thesis are based on computational modeling (Bubblesim software) and as a future continuation we plan to verify the simulation results with vitro studies.

Neste trabalho serão discutidas novas ferramentas para a construção de um espectrômetro de Ressonância Magnética (RM) totalmente digital. A motivação parte das dificuldades encontradas pelos pesquisadores no momento de programar um equipamento de RM, incluindo a falta de ferramentas para desenvolvimento de metodologias, as quais não são oferecidas pelos softwares atuais. Em particular tratamos do desenvolvimento de uma biblioteca, a PyMR (Python Magnetic Resonance), de uma API (Application Program Interface) e de um IDE (Integrated Development Environment). Nesta estrutura, a biblioteca PyMR é o front-end para programação e setup dos equipamentos de RM enquanto a API constitui o back-end. O IDE, por sua vez, é uma ferramenta de auxílio especializado para criação e gerenciamento das metodologias e protocolos de RM de forma funcional e amigável. O desenvolvimento baseado no estado-da-arte das tecnologias de Computação e Ressonância Magnética garante a qualidade, robustez, adaptabilidade e ainda assim, a simplicidade para uso dos menos experientes. Para a validação do sistema, além de métricas de software, foi montada uma sequência de pulsos conhecida como CPMG (Carr-Purcell-Meiboom-Gill) executada no espectrômetro local sobre uma amostra de CuSO4 em solução, o qual mostrou valores de T2 compatíveis com os valores esperados. Os resultados do novo sistema mostram sua capacidade de atender as principais exigências dos usuários e desenvolvedores de metodologias de RM, oferecendo um amplo conjunto de ferramentas. Em suma, este projeto provê a estrutura básica e funcional de uma nova forma de se programar e utilizar equipamentos de RM, gerando um poderoso instrumento para a pesquisa na área. / In this study we discuss new tools for the building of a fully digital Magnetic Resonance (MR) spectrometer. The research was motivated by several difficulties experienced by researchers in programming MR machines, which include the lack of tools for the development of methodologies that are not currently offered by companies. In particular, we treat the development of a library, PyMR (Python Magnetic Resonance), an API (Application Program Interface) and an IDE (Integrated Development Environment). In this structure, the PyMR library acts as a front-end for MR equipment programming and setup while the API is a back-end. Finally, the IDE is a user-friendly tool that helps the developer to create and manage methodologies and protocols. The state-of-the-art of Computer Sciences and Magnetic Resonance technologies adopted here has ensured the quality, robustness and adaptability keeping simplicity for non-experienced users. For the validation of the system, besides software metrics, a pulse sequence known as CPMG (Carr-Purcell-Meiboom-Gill) was assembled and performed on an onsite spectrometer, using a solution of CuSO4 as a sample, which exhibited compatible T2 values. The results show that the system can meet the main requirements of both users and developers and offer a large set of tools. This project provides a basic and functional structure of a new way to program and use the MR equipment and a powerful tool for researchers in this area.

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.<p>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.<p>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. <p>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.<p>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.<p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

L’imagerie par résonance magnétique (IRM) est un outil important pour l’investigation qualitative et quantitative de la physiologie du cerveau. L’investigation de l’activité neuronale à l’aide de cette modalité est possible grâce à la détection de changements hémodynamiques qui surviennent de manière concomitante aux activités de signalisation des neurones, tels l’augmentation régionale du débit sanguin cérébral (CBF) ou encore la variation de la concentration de désoxyhémoglobine dans les vaisseaux veineux. Pour étudier la formation de contrastes fonctionnels qui découlent de ces phénomènes, deux séquences de pulses ont été développées en vue d’expériences en IRM fonctionnelle (IRMf) visant l’imagerie du signal oxygéno-dépendant BOLD ainsi que de la perfusion. Le premier objectif de cette thèse fut le développement d’une séquence de type écho-planar (EPI) permettant l’acquisition entrelacée d’images en mode échos de gradient (GRE-EPI) ainsi qu’en mode échos de spins (SE-EPI) pour l’évaluation de la performance de ces deux méthodes d’imagerie au cours d’une expérience en IRMf BOLD impliquant l’utilisation d’un stimulus visuel chez 4 sujets adultes sains. Le deuxième objectif principal de cette thèse fut le développement d’une séquence de marquage de spins artériels employant un module de marquage fonctionnant en mode pseudo-continu (pCASL) pour la quantification du CBF au repos. Cette séquence fut testée chez 3 sujets adultes en bonne santé et sa performance fut comparée à celle d’une séquence similaire développée par un groupe de recherche extérieur. Les résultats de l’expérience portant sur le contraste BOLD indiquent une supériorité de la performance du mode GRE-EPI vis-à-vis celle du mode SE-EPI en termes des valeurs moyennes du pourcentage de l’ampleur d’effet et du score t associés à l’activité neuronale en réponse au stimulus. L’expérience visant la quantification du CBF démontra la capacité de la séquence pCASL développée au cours de ce projet de calculer des valeurs de la perfusion de la matière grise ainsi que du cerveau entier se retrouvant dans une plage de valeurs qui sont physiologiquement acceptables, mais qui demeurent inférieures à celles obtenues par la séquence pCASL développée par le groupe de recherche extérieur. Des expériences futures seront effectuées pour optimiser le fonctionnement des séquences présentées dans ce mémoire en plus de quantifier l’efficacité d’inversion de la séquence pCASL. / Magnetic resonance imaging (MRI) is an important tool for the qualitative and quantitative investigation of brain physiology. The investigation of neuronal activation using this modality is made possible by the detection of concomitantly-arising hemodynamic changes in the brain’s vasculature, such as localized increases of the cerebral blood flow (CBF) or the variation of the concentration of paramagnetic deoxyhemoglobin in venous vessels. To study the formation of functional contrasts that stem from these changes in MRI, two pulse sequences were developed in this thesis to carry out experiments in blood oxygenation level dependent (BOLD) and perfusion functional MRI (fMRI). The first objective laid out in this work was the development of an echo planar imaging (EPI) sequence permitting the interleaved acquisition of images using gradient-echo EPI and spin-echo EPI to assess the performances of these imaging techniques in a BOLD fMRI experiment involving a visual stimulation paradigm in 4 healthy adult subjects. The second main objective of this thesis was the development of a pseudo-continuous arterial spin labelling (pCASL) sequence for the quantification of cerebral blood flow (CBF) at rest. This sequence was tested on 3 healthy adult subjects and compared to an externally-developed pCASL sequence to assess its performance. The results of the BOLD fMRI experiment indicated that the performance of GRE-EPI was superior to that of SE-EPI in terms of the average percent effect size and t-score associated with stimulus-driven neuronal activation. The CBF quantification experiment demonstrated the ability of the in-house pCASL sequence to compute values of CBF that are within a range of physiologically-acceptable values while remaining inferior to those computed using the externally-developed pCASL sequence. Future experiments will focus on the optimization of the sequences presented in this thesis as well as on the quantification of the pCASL sequence’s labelling efficiency.

Collateral blood flow is the compensatory flow of blood to the tissue through secondary channels when the primary channel is compromised. It is of vital importance in cerebrovascular disease where collateral flow can maintain large regions of brain tissue which would otherwise have suffered ischaemic damage. Traditional x-ray based techniques for visualising collateral flow are invasive and carry risks to the patient. In this thesis novel magnetic resonance imaging techniques for performing vessel-selective labelling of brain feeding arteries are explored and developed to reveal the source and extent of collateral flow in the brain non-invasively and without the use of contrast agents. Vessel-encoded pseudo-continuous arterial spin labelling (VEPCASL) allows the selective labelling of blood water in different combinations of brain feeding arteries that can be combined in post-processing to yield vascular territory maps. The mechanism of VEPCASL was elucidated and optimised through simulations of the Bloch equations and phantom experiments, including its sensitivity to sequence parameters, blood velocity and off-resonance effects. An implementation of the VEPCASL pulse sequence using an echo-planar imaging (EPI) readout was applied in healthy volunteers to enable optimisation of the post-labelling delay and choice of labelling plane position. Improvements to the signal-to-noise ratio (SNR) and motion-sensitivity were made through the addition of background suppression pulses and a partial-Fourier scheme. Experiments using a three-dimensional gradient and spin echo (3D-GRASE) readout were somewhat compromised by significant blurring in the slice direction, but showed potential for future work with a high SNR and reduced dropout artefacts. The VEPCASL preparation was also applied to a dynamic 2D angiographic readout, allowing direct visualisation of collateral blood flow in the brain as well as a morphological and functional assessment of the major cerebral arteries. The application of a balanced steady-state free precession (bSSFP) readout significantly increased the acquisition efficiency, allowing the generation of dynamic 3D vessel-selective angiograms. A theoretical model of the dynamic angiographic signal was also derived, allowing quantification of blood flow through specified vessels, providing a significant advantage over qualitative x-ray based methods. Finally, these methods were applied to a number of patient groups, including those with vertebro-basilar disease, carotid stenosis and arteriovenous malformation. These preliminary studies demonstrate that useful clinical information regarding collateral blood flow can be obtained with these techniques.

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