This research has investigated proton-coupled electron transfer (PCET) of quinone/hydroquinone and other simple organic PCET species for the purpose of furthering the knowledge of the thermodynamic and kinetic effects due to reduction and oxidation of such systems. Each of these systems were studied involving the addition of various acid/base chemistries to influence the thermodynamics and kinetics upon electron transfer. It is the expectation that the advancement of the knowledge of acid/base catalysis in electrochemistry gleaned from these studies might be applied in fuel cell research, chemical synthesis, the study of enzymes within biological systems or to simply advance the knowledge of acid/base catalysis in electrochemistry. Furthermore, it was the intention of this work to evaluate a system that involved concerted-proton electron transfer (CPET), because this is the process by which enzymes are believed to catalyze PCET reactions. However, none of the investigated systems were found to transfer an electron and proton by concerted means. Another goal of this work was to investigate a system where hydrogen bond formation could be controlled or studied via electrochemical methods, in order to understand the kinetic and thermodynamic effects complexation has on PCET systems. This goal was met, which allowed for the establishment of in situ studies of hydrogen bonding via 1H-NMR methods, a prospect that is virtually unknown in the study of PCET systems in electrochemistry, yet widely used in fields such as supramolecular chemistry. Initial studies involved the addition of Brønsted bases (amines and carboxylates) to hydroquinones (QH2’s). The addition of the conjugate acids to quinone solutions were used to assist in the determination of the oxidation processes involved between the Brønsted bases and QH2’s. Later work involved the study of systems that were initially believed to be less intricate in their oxidation/reduction than the quinone/hydroquinone system. The addition of amines (pyridine, triethylamine and diisopropylethylamine) to QH2’s in acetonitrile involved a thermodynamic shift of the voltammetric peaks of QH2 to more negative oxidation potentials. This effect equates to the oxidation of QH2 being thermodynamically more facile in the presence of amines. Conjugate acids were also added to quinone, which resulted in a shift of the reduction peaks to more positive potentials. To assist in the determination of the oxidation process, the six pKa’s of the quinone nine-membered square scheme were determined. 1H-NMR spectra and diffusion measurements also assisted in determining that none of the added species hydrogen bond with the hydroquinones or quinone. The observed oxidation process of the amines with the QH2’s was determined to be a CEEC process. While the observed reduction process, due to the addition of the conjugate acids to quinone were found to proceed via an ECEC process without the influence of a hydrogen bond interaction between the conjugate acid and quinone. Addition of carboxylates (trifluoroacetate, benzoate and acetate) to QH2’s in acetonitrile resulted in a similar thermodynamic shift to that found with addition of the amines. However, depending on the concentration of the added acetate and the QH2 being oxidized, either two or one oxidation peak(s) was found. Two acetate concentrations were studied, 10.0 mM and 30.0 mM acetate. From 1H-NMR spectra and diffusion measurements, addition of acetates to QH2 solutions causes the phenolic proton peak to shift from 6.35 ppm to as great as ~11 ppm, while the measured diffusion coefficient decreases by as much as 40 %, relative to the QH2 alone in deuterated acetonitrile (ACN-d3). From the phenolic proton peak shift caused by the titration of each of the acetates, either a 1:1 or 1:2 binding equation could be applied and the association constants could be determined. The oxidation process involved in the voltammetry of the QH2’s with the acetates at both 10.0 and 30.0 mM was determined via voltammetric simulations. The oxidation process at 10.0 mM acetate concentrations involves a mixed process involving both oxidation of QH2 complexes and proton transfer from an intermediate radical species. However, at 30.0 mM acetate concentrations, the oxidation of QH2-acetate complexes was observed to involve an ECEC process. While on the reverse scan, or reduction, the process was determined to be an CECE process. Furthermore, the observed voltammetry was compared to that of the QH2’s with amines. From this comparison it was determined that the presence of hydrogen bonds imparts a thermodynamic influence on the oxidation of QH2, where oxidation via a hydrogen bond mechanism is slightly easier. In order to understand the proton transfer process observed at 10.0 mM concentrations of acetate with 1,4-QH2 and also the transition from a hydrogen bond dominated oxidation to a proton transfer dominated oxidation, conjugate acids were added directly to QH2 and acetate solutions. Two different acetate/conjugate acid ratios were focused on for this study, one at 10.0 mM/25.0 mM and another at 30.0 mM/50.0 mM. The results of voltammetric and 1H-NMR studies were that addition of the conjugate acids effects a transition from a hydrogen bond oxidation to a proton transfer oxidation. The predominant oxidation species and proton acceptor under these conditions is the uncomplexed QH2 and the homoconjugate of the particular acetate being studied, respectively. Furthermore, voltammetry of QH2 in these solutions resembles that measured with the QH2’s and added amines, as determined by scan rate analysis. In an attempt to understand a less intricate redox-active system under aqueous conditions, two viologen-like molecules were studied. These molecules, which involve a six-membered fence scheme reduction, were studied under buffered and unbuffered conditions. One of these molecules, N-methyl-4,4’-bipyridyl chloride (NMBC+), was observed to be reduced reversibly, while the other, 1-(4-pyridyl)pyridinium chloride (PPC+), involved irreversible reduction. The study of these molecules was accompanied by the study of a hypothetical four-membered square scheme redox system studied via digital simulations. In unbuffered solutions each species, both experimental and hypothetical, were observed to be reduced at either less negative (low pH) or more negative (high pH), depending on the formal potentials, pKa’s of the particular species and solution pH. The presence of buffer components causes the voltammetric peaks to thermodynamically shift from a less negative potential (low pH buffer) to a more negative potential (high pH buffer). Both of these observations have been previously noted in the literature, however, there has been no mention, to our knowledge, of kinetic effects. In unbuffered solutions the reduction peaks were found to separate near the pKa,1. While in buffered solutions, there was a noted peak separation throughout the pH region defined by pKa’s 1 and 2 (pKa,1 and pKa,2) of the species under study. The cause for this kinetic influence was the transition from a CE reduction at low pH to an EC reduction process at high pH in both buffered and unbuffered systems. This effect was further amplified via the study of the hypothetical species by decreasing the rate of proton transfer. In an effort to further this work, some preliminary work involving the attachment of acid/base species at the electrode surface and electromediated oxidation of phenol-acetate complexes has also been studied. The attachment of acid/base species at the surface is believed to assist in the observation of heterogeneous acid/base catalysis, similar to that observed in homogeneous acid/base additions to quinone/hydroquinone systems. Furthermore, our efforts to visualize a concerted mechanism are advanced in our future experiments involving electromediated oxidation of phenol-acetate complexes by inorganic species. It may be possible to interrogate the various intermediates more efficiently via homogeneous electron-proton transfer rather than heterogeneous electron transfer/homogeneous proton transfer.

No description available.

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.

In this thesis, optimum current injection strategy for Magnetic Resonance Electrical Impedance Tomography (MREIT) is studied. Distinguishability measure based on magnetic flux density is defined for MREIT. Limit of distinguishability is analytically derived for an infinitely long cylinder with concentric and eccentric inhomogeneities. When distinguishability limits of MREIT and Electrical Impedance Tomography (EIT) are compared, it is found that MREIT is capable of detecting smaller perturbations than EIT. When conductivities of inhomogeneity and background object are equal to 0.8S and 1S respectively, MREIT provides improvement of %74 in detection capacity. Optimum current injection pattern is found based on the distinguishability definition. For 2-D cylindrical body with concentric and eccentric inhomogeneities, opposite drive provides best result. As for the 3-D case, a sphere with azimuthal symmetry is considered. Distinguishability limit expression is obtained and optimum current injection pattern is again opposite drive. Based these results, optimum current injection principles are provided and Regional Image Reconstruction (RIR) using optimum currents is proposed. It states that conductivity distribution should be reconstructed for a region rather than for the whole body. Applying current injection principles and RIR provides reasonable improvement in image quality when there is noise in the measurement data. For the square geometry, when SNR is 13dB, RIR provides decrement of nearly %50 in conductivity error rate of small inhomogeneity. Pulse sequence optimization is done for Gradient Echo (GE) and it is compared with Spin Echo (SE) in terms of their capabilities for MREIT.

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.

The task of this thesis is to study methods for the acquisition perfusní imaging based on dynamic MR imaging with T1 contrast. It describes methods of measurement of T1 relaxation time and the possibility of evaluating the results. It further describes the phantoms and their use. And it is here mentioned for the dynamic acquisition protocol perfusní imaging. There is also described in detail created a program for automatic control of the NMR system. In the experimental measurements are performed on static and dynamic phantom, are also evaluated perfusion parameters from the Flash sequence.

Discrete and Continuous spatial encoding methods are described with details of understanding principles and practical implications. Step by step experimental op- timization procedure of these methods to achieve slice selection are also discussed. In the subsequent chapters we use these methods for different applications. Spin-lattice relaxation parameters of NMR active nuclei provide valuable infor- mation on molecular dynamics. Single scan selective excitation methods of mea- surement of T1 result in significant reduction of time compared to the standard inversion recovery method and are attractive tools of applications in `Real time' NMR investigations of biological and chemical processes. It is shown here that the addition of the gradient echo following the selective excitation not only significantly improves the S/N ratio, but also makes GESSIR a versatile pulse sequence. Using this sequence, T1 values ranging from 2 s to 56 s have been measured with accuracy comparable to the standard IR experiment. This indicates that it is possible to utilize GESSIR for a wide range of molecules containing protons and hetero nuclei with medium to long T1 relaxation times as a routine NMR technique. The utility of the technique for studying other relaxation parameters has also been demonstrated. It may be mentioned that for measurement of relaxation parameters routinely, a few well-chosen points are enough. A fine selection of large number of experimental points could be useful when high accuracy is required or Chapter 3. GESSIR 91 for applications where certain property of the system investigated is changing in a continuous manner spatially and requires large number of slices to be selected as discussed in the next chapter. The long duration of time-honored two dimensional experiments is reduced to fraction of seconds by employing the ultrafast encoding experiments. Main com- plications in making the UF experiments available for routine use were the limited spectral widths and resolution in both UF and conventional dimensions. Various developments have been made in the path of improvements in increasing the spectral width in UF dimension. Of these, two experimental methods that are already proposed, namely the folding of peaks into the observable spectral window and the interleaved acquisition which doubles the spectral widths in both dimensions. The integration of covariance processing with ultrafast technique yields better correlated spectrum with considerable improvement in resolution. The effectiveness of the new processing is demonstrated for UF COSY experiments which can be easily extended to other ultrafast homonuclear experiments like TOCSY, NOESY as well as multi dimensions. The proposed processing method is an initial step to work on improving resolutions of UF data and making the ease of applicability of ultrafast spectroscopy as a routine multidimensional NMR. At the same time of this work W. Qui et.al [268] proposed a processing method based on covariance and pattern recognition for improving resolutions of spatially encoded data. They used pattern recognition algorithm also for avoiding the artifacts due to very low resolution data available with the UF experiment. They implemented the method UF TOCSY spectra and shown resolution improvement with the covariance pro- cessing for relatively more number of detection gradients which is many times hardware limited. Our method of covariance data processing is essentially same as that of Qui, less number of acquisition gradients were used in our processing, linear prediction and apodization concepts were utilized and the artifacts arise due mismatch of datas with positive and negative acquisition gradients are minimized by shifting one the data. In conclusion new methods of processing/the combination of various processing methods of the ultrafast data have the scope of improving the quality of ultrafast NMR spectra.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20564号 / 医博第4249号 / 新制||医||1022(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 妹尾 浩, 教授 鈴木 実 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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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.