Typescript Includes 1 report by the author Includes bibliographical references The scope of the Reformatsky reaction of imines with a_-bromoesters and zinc has been investigated. The stereochemistry 2-azetidinones (β_-lactams) formed has been determined by nuclear magnetic resonace spectroscopy.

Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1966. / Typescript. Includes 1 report by the author. Includes bibliographical references.

Cardiovascular magnetic resonance imaging (MRI) is a well established technique in clinical cardiology. Different MRI sequences are routinely used to assess cardiac anatomy, function, viability and other parameters that aid diagnosing cardiac disease. Conversely, cardiac magnetic resonance spectroscopy (MRS), the only available method for a non-invasive study of human cardiac metabolism, has not evolved into a clinical tool yet. The combination of both techniques holds great potential to gain insight into the causality of cardiomyopathy diseases or other medical conditions with high cardiovascular risk profile, like diabetes or obesity and improve the clinical management of cardiac diseases. Nowadays, high field clinical MR systems have the great potential of improving the low spatial and temporal resolution and reproducibility of MRS. The aim of this thesis was to develop and implement a cardiac 1H-MRS method at 3 T that can be applied in clinical routine for the assessment of creatine and lipid levels in the human myocardium. The methodological developments to advance cardiac MRS are presented first. A robust 1H-MRS method comprising an optimized single-voxel technique, phased-array coil combination routine, optimized water suppression, breath-hold averaging and post-processing methods were developed. First, reproducibility and feasibility of the method were validated in vivo by acquiring 1H-MRS of the liver in almost one hundred healthy subjects. Subsequently, myocardial lipids levels were obtained in healthy volunteers by single breath-hold 1H-MRS triggered to mid-diastole, showing good reproducibility in an acquisition time less than 12 s. The good spectral resolution achieved using this method was demonstrated by the ability to differentiate for the first time two pools of myocardial lipids in spectra from the septum of patients with suspected myocardial lipid excess. Finally, creatine levels for healthy volunteers were investigated using multiple breath-hold acquisitions. Thus, this study shows the practicality and feasibility to incorporate this rapid cardiac 1H-MRS method into clinical studies of the human myocardium.

One-color resonance two-photo ionization (R2PI) spectra of mixed clusters of styrene molecule (S) with polar molecules [water (W), methanol (M), ethanol (E), and trifuoroethanol (T)] were measured through the S1←S0 transition of the styrene molecule. The spectra reveal a rapid increase in complexity with the number of polar molecules in the cluster, associated with van der Waal modes and isomeric forms. The spectral shifts of the cluster origins from the S1-S0 transition of the bare styrene molecule reflect the nature of the intermolecular interactions within the binary clusters. The obtained R2PI spectra xv were compared with the spectra of the analogous benzene containing clusters. The styrene-water and the styrene-methanol complexes exhibited very different spectral shifts and structures as compared to the benzene-water and benzene-methanol complexes, respectively. The favorable interactions of polar molecules with the olefin group of styrene may explain the strong inhibition effects of exerted by small concentrations of water and alcohols on the cationic polymerization of styrene. Size-specified intracluster proton transfer reactions were observed for mixed clusters of styrene dimer with water, methanol and ethanol molecules. It was proposed that the polar molecules tend to aggregate around the olefin center, which promotes the transfer of the charge from the propagating chain to the hydrogen-bonded polar molecules subcluster. The minimum number of polar molecules required for a proton transfer to take place exothermically depends on the proton affinity of the polar molecules subcluster. The estimated upper limit value for the proton affinity of styrene dimer radical was evaluated based on the energetic of the proton transfer reaction to be ≤ 220.4 kcal/mol. No intracluster reaction was observed for styrene-trifluoroethanol (STn) system. In order to provide a comparison between the styrene and benzene systems, the benzene-ethanol (BEn) and benzene-trifluoroethanol (BTn) clusters were studied by using the R2PI technique via the 6¹0 transition of the benzene molecule. Both dissociative electron transfer and dissociative proton transfer reactions were observed within the BEn clusters, where n = 2 and 3, respectively. Proton transfer reactions were observed following dissociative electron transfer reactions within the (BTn) clusters, where n = 4, to generate the protonated clusters (H+Tn).

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

L’imagerie et la spectroscopie par résonance magnétique nucléaire (IRM et SRM) sont des méthodes non-invasives qui ont le potentiel d’estimer in vivo la quantité et la qualité des adiposités abdominales. Le contexte scientifique et clinique de ce manuscrit s’articule autour de l’étude de surnutrition « Poly-Nut » dont l’un des objectifs est d’analyser les évolutions des tissus adipeux (TA) dans une phase rapide de prise de poids. L’originalité et la complexité de cette thèse résident dans le développement, l’adaptation et la comparaison de plusieurs méthodes quantitatives d’IRM et de SRM, pour l’étude du signal lipidique dans un contexte clinique à 3T. La fiabilité et la validation des mesures obtenues in vivo par ces techniques font ici l’objet d’une étude approfondie. Pour l’analyse quantitative du signal de spectroscopie, différentes méthodes existantes ont été comparées à celle développée spécifiquement pour notre étude clinique. L’estimation paramétrique par moindres carrés non linéaires appliquée aux spectres RMN des lipides peut conduire, selon la fonction modèle utilisée, à un problème non linéaire mal posé. Nous montrons alors que l’utilisation d’un modèle simplifié se fondant sur la structure d’une chaine de triglycéride, comme utilisé récemment en imagerie quantitative, constitue une solution valide au regard de l’état de l’art. Ensuite différentes méthodes (IRM, SRM, Dual Energy X-ray absorptiometry, chromatographie en phase gazeuse) ont été utilisées pour caractériser les TA sous-cutanés et viscéraux. Le suivi par IRM du contenu lipidique du foie ainsi que du volume et de la composition en acide gras des TA à partir d’une unique acquisition en multi-écho de gradient est démontré. Enfin des développements expérimentaux menés parallèlement à l’étude clinique sur un imageur préclinique à 4,7T, comparent différentes stratégies d’encodage du déplacement chimique par imagerie et caractérisent des méthodes SRM pour estimer in vivo la proportion d’omégas-3 dans les chaînes d’acides gras. / Magnetic resonance imaging and spectroscopy (MRI and MRS) are non-invasive methods that have the potential to estimate in vivo the quantity and the quality of abdominal adipose tissues (AT). The scientific and clinical context of this thesis is based on an overfeeding study entitled "Poly-Nut". One of the main objectives of this study is to analyze changes in adipose tissues in a rapid phase of weight gain. The originality and complexity of this thesis rely in the development, adaptation and comparison of several quantitative methods of MRI and MRS, for the study of lipid signal, in a clinical context, at 3T. The reliability and the validation of the measurements obtained in vivo using these techniques are the main subject of this PhD thesis. For the quantitative analysis of the spectroscopy signal, different existing methods have been compared to those developed specifically for our clinical study. According to the model function used, the nonlinear-least-squares parametric estimation applied to the lipid spectra can lead to an ill-posed nonlinear problem. We demonstrated that the use of a simplified model based on the structure of a triglyceride chain, as recently used in quantitative imaging, was a valid solution regarding the state of the art. Then different methods (MRI, MRS, Dual Energy X-ray absorptiometry, gas chromatography) were used to characterize the subcutaneous and visceral AT. We demonstrated the feasibility of MRI to follow the lipid content in the liver as well as the volume and the fatty acid composition of AT using a single multiple gradient-echo acquisition. Finally, experimental developments were carried out in parallel with the clinical study, on a 4.7T preclinical system, first, to compare different strategies for encoding the chemical shift using imaging and, secondly, to characterize MRS methods for in vivo estimation of the relative proportion of omega-3 among all fatty acids.