Phosphorus (³¹P) metabolites are emerging liver disease biomarkers. This work aims to develop a quantification protocol for human hepatic ³¹P magnetic resonance spectroscopy (MRS) at 7 tesla (T). It should have high SNR, deliver robust measurements of metabolite concentrations with high reproducibility, and be feasible to use in clinical studies. This will allow detailed characterization of liver metabolism in diseases such as cirrhosis, increasing the utility of ³¹P-MRS as a clinical tool. A 3D chemical shift imaging method using a 16 channel ³¹P array at 7 T is chosen to give high SNR ³¹P spectra from the human liver in vivo, while also providing good spatial localization and spectral resolution. The Oxford Spectroscopy Analysis (OXSA) toolbox, our MATLAB-based processing software package, is introduced and adaptations for analysis of liver spectra are described. Five volunteers were scanned to determine T₁s for the ten visible ³¹P metabolites. Simulations were used to determine design criteria for calibration phantoms at 1.5, 3 and 7 T. I compare three candidate approaches to give "absolute" concentrations in mmol/L wet tissue using a 10 cm loop coil, and then extend these approaches to data acquired using the 16 element receive array. The final protocol was applied to data acquired in ten healthy volunteers and eleven patients with cirrhosis to determine reproducibility and the differences between healthy and diseased livers. This protocol allows distinction between healthy and cirrhotic livers with 90% specificity and sensitivity, using cut-offs in either Î3-adenosine triphosphate or inorganic phosphate concentrations. This ³¹P-MRS absolute quantification protocol is an important first step in fully utilising the increased SNR afforded by the 7 T scanner, offering valuable insight into liver metabolism, and paving the way for other novel ³¹P-MRS methods to be developed in the liver at 7 T.

Magnetic resonance imaging (MRI) is a valuable research and clinical imaging modality for the non-invasive detection and characterization of cerebral ischemia. Specifically, diffusion-weighted imaging (DWI), which derives image contrast based on the diffusion of endogenous water molecules, is sensitive to cerebral ischemia within minutes of the onset of stroke. In combination with perfusion-weighted imaging (PWI) and T2-weighted imaging (T2WI), DWI can be used to characterize the temporal and spatial evolution of cerebral ischemia. The primary role of this dissertation is to outline several studies that investigate DWI, PWI, and T2WI changes in a rat stroke model of transient cerebral ischemia. Secondarily, this dissertation will introduce the method and results of an experiment designed to elucidate the relative roles of the intracellular (IC) or extracellular (EC) spaces to the water diffusion coefficient changes that occur as a result of cerebral ischemia. The use of MRI to detect cerebral ischemia is well established; however, the ability to distinguish between reversibly and irreversibly damaged tissues is limited. It has been shown in temporary focal ischemia models that the DWI abnormality (manifested as an image hyperintensity in the DWI) can be resolved if reperfusion is performed soon after the onset of the stroke. Initial studies suggested that the renormalization of water diffusion was associated with permanent restoration of cellular function (i.e., infarction was prevented). However, subsequent studies demonstrated that the disappearance of the acute ischemic lesion following reperfusion is not necessarily permanent and is related to the duration of the transient insult. Following short occlusions [e.g., 10 minutes in a rat middle cerebral artery occlusion (MCAO) model], there is complete tissue renormalization and restoration of normal neurological function. In contrast, following long periods of occlusion (e.g., 90 minutes), there are areas of the brain that do not recover and progress to infarction without delay. Intermediate durations of occlusion (e.g., 30 minutes) exhibit complete renormalization in all regions of ischemia; however, following several hours there is a gradual, secondary decline of the water diffusion coefficient values within the regions initially defined as abnormal. In this dissertation, the significant temporal and spatial heterogeneity in the secondary diffusion changes will be described and evaluated. Ultimately, MR techniques may provide valuable information regarding the response of tissue to transient ischemia as well as potential avenues for therapeutic intervention, which would have major clinical benefit. The significant changes in the apparent diffusion coefficient (ADC) of water that occur in ischemic brain are still not well understood. The leading hypothesis suggests that cellular swelling associated with the failure of the ionic gradient across the cell membrane results in an increase in EC tortuosity of the diffusion paths. Another theory suggests that the influx of fast-diffusing EC water, that occurs during cellular swelling, increases the proportion of water in the IC space, which is more restricted and viscous than the EC space. The final experiment presented herein demonstrates that significant cellular swelling remains in the regions of renormalized of ischemic ADC values that occur following reperfusion in transient ischemia. In short, the changes in the ADC values are not only the result of cellular swelling. Since conventional MR data contains the combined signals from the IC and EC spaces, it is difficult to determine the separate roles of these two compartments to the overall changes in water ADC. First, using a yeast-cell model, a method for separating the NMR signals is introduced. This method utilizes differences in the compartmental relaxation properties to isolate the MR signals from IC and EC spaces, and then secondarily the diffusion coefficients can be calculated. Using a modified version of this method, the experiment was performed in normal and ischemic rat brain. Intracerebroventricular (ICV) infusion of an MR contrast reagent (CR) was used to isolate IC T1, T2, and ADC values in vivo in normal and middle cerebral artery occluded (MCAO) rats using volume-localized, diffusion-weighted inversion-recovery spin-echo (DW-IRSE) spectroscopy and diffusion-weighted echo-planar imaging (DW-EPI). The presence of the EC contrast reagent (CR) selectively enhances the relaxation of water in the EC space and allows the IC and EC signal contributions to be separated based on T1-relaxation time differences between the two compartments. The results presented in this dissertation suggest that the IC ADC value is the major determinant of the overall ADC value measured in the normal rat brain. Further, the data suggests that the ADC decline experienced during acute ischemia is dictated largely by changes in the IC ADC, possibly due to failure of energy-dependent IC microcirculation (cytoplasmic streaming).

"Diffusion-weighted nuclear magnetic resonance has gained widespread use in the characterization of various diseases. Developments in the area of porous media theory have been successfully transferred and adapted for the use in biological tissue. Measurement of the displacement of diffusing water molecules can reveal structural information about the environment in which the molecules translate. The return-to-the-origin (RTO) probability and the apparent diffusion coefficient (ADC) are based on the diffusion behavior of water molecules in a restricted environment. Water molecules in restricted space have smaller displacements, for a given diffusion time, than water molecules diffusing in bulk solution. The cell membranes and organelles in healthy biological tissue impart more restrictions on diffusing water molecules as compared to necrotic tumor tissue. In necrotic tissue the degradation of cellular structures by auto- and/or heterolysis allows water molecules to diffuse over larger distances without encountering restrictions. The spectroscopic measurement of the RTO probability and the RTO enhancement in RIF-1 tumors showed that the RTO probability is sensitive to these changes in structure. The study showed that smaller tumors, which are less necrotic, have a larger RTO probability and enhancement than larger RIF-1 tumors with a higher fraction of necrotic tumor tissue. Extension of the methodology to NMR imaging was used to answer the question if the RTO probability can provide spatial information about the necrotic area within RIF-1 tumors. The necrotic area measured by the ADC and histology were compared. While neither ADC or RTO could show its superiority over the other, both methods showed a good correlation between their mean values and the necrotic area fraction as measured by histology. The mean ADC and the mean RTO enhancement had a correlation with the necrotic tumor fraction, as determined by histology, of r = 0.86 and r = -0.82, respectively. Conventional T2-weighted images of the same tumor slice showed a poorer correlation (r = 0.62) with the necrotic fraction and no visual agreement with the histology. The general features of the ADC and RTO enhancement were in agreement with histology, however, more exact comparisons where not possible due to the large differences in slice thickness between the two techniques. Structural changes similar to those caused by tumor tissue necrosis can be induced by chemo- and radiation therapy and ADC and RTO enhancement were used to monitor these changes non-invasively. RIF-1 tumors were grown on the hind leg of C3H mice and monitored daily by diffusion-weighted MRI. ADC and RTO-enhancement maps were created using data acquired from control animals and animals treated with 100 mg/kg 5-Fluorouracil. Both ADC and RTO proved to be useful in the early detection of the efficacy of treatment as well as for monitoring the progress of therapy. Diffusion measurements by pulsed-field-gradient (PFG) MRI have become an important tool for detecting of pathophysiological changes caused by cancer and stroke. The increasing popularity of diffusion measurements has initiated their use on clinical MRI systems that have limited magnetic-field-gradient strength. These limitations make it necessary to lengthen the diffusion-gradient duration to ensure sufficient signal attenuation for calculating the ADC. Unfortunately, increasing of the diffusion-gradient duration to a large extent violates the theoretical model used in the ADC calculation. The diffusion measurements are not performed in the finite pulse width regime, but rather in the constant gradient regime, requiring a different interpretation of the results. Examination of the differences in the measured diffusion coefficient showed that increasing both the diffusion-gradient duration and the echo time have a significant impact on the results of a diffusion measurement. A different way to assess changes in RIF-1 tumors as a function of treatment is the measurement of the tissue oxygen status. Cell hypoxia has long been linked with treatment resistivity and reoccurrence in cancers, where the oxygen status is a determining factor of treatment outcome. Perfluorocarbons (PFC's) have been used successfully to assess the tumor oxygen status in the past, but required a large MRI slice thickness due to compensate for the low PFC concentration. The tissue oxygen status of the tumor is assessed by intravenous injection of a PFC that is subsequently sequestered in the tumor. The measurement of the T1-relaxation time of the PFC allows the calculation of the oxygen content, which is linearly related to the relaxivity and the temperature. Fluorine-19, multiple-slice, inversion-recovery echo-planar imaging (EPI) allowed high spatial resolution assessment of the tissue oxygen status over the entire tumor. The results demonstrated that there is a large variation in tissue oxygenation between adjacent slices. Comparison of the oxygen distribution between various tumors also showed that there is no common pattern in the spatial distribution of oxygen within the tumor. Monitoring of the oxygen status during chemotherapy showed an increase in hypoxic tissue and a reduction in tumor size in response to the toxicity of the chemotherapeutic agent. As the effects of the treatment subsided, rapid cell proliferation caused the tumor to regrow and a subsequent decrease in tissue oxygen tension was observed. The study clearly demonstrated the changes in oxygen tension in response to chemotherapy and the need for multi-slice MRI acquisition at high spatial resolution to detect these changes."

Research applications of nuclear magnetic resonance (NMR) span a broad range of fields and disciplines. The work presented in this dissertation attests to this fact. Specifically, the research topics discussed in the body of this work employ NMR spectroscopy and imaging to characterize the water diffusion and NMR relaxation times ex vivo in rabbit Achilles tendon and, in a clinical setting, employ functional magnetic resonance imaging (fMRI) to investigate the behavior of different neural networks over a period of sustained activity. In the ex vivo rabbit Achilles tendon work, a series of studies were performed. First, the diffusion-time dependence of the water apparent diffusion coefficient (ADC) was characterized in a spectroscopic mode with the samples subjected to different states of tensile loading. The results of this study demonstrated: (1) the anisotropy of the diffusion of water through tendon; (2) the ADC is diffusion-time dependent; (3) the values of the ADC(tdif) curve increased with tensile loading; (4) a change at the short diffusion-time points that is consistent with the interpretation of a load-induced increase in the collagen fibril packing density; and (5) an increase in the water ADC at long diffusion times is hypothesized to be due to T1 editing. To further investigate these issues, another series of ex vivo rabbit Achilles tendon experiments was performed that employed NMR imaging to spatially characterize the water ADC, T1 and T2 relaxation time constants. As with the spectroscopic work, these studies were also conducted with the tendon samples subjected to different states of tensile loading. The results from these imaging experiments demonstrate: (1) two regions with distinct differences in signal intensity across the tendon: a thin region of high signal intensity at the peripheral rim of the tendon that encircles a region of low signal intensity in the central core of the tendon; (2) a higher diffusion anisotropy ratio in the tendon central core relative to the peripheral rim; (3) upon tensile loading, significant increases in the ADC of water in the peripheral rim region and a corresponding increase in a measure of the change in proton density in the rim region, consistent with the hypothesis that tensile loading causes extrusion of water from the core to the rim region of the tendon; (4) this water extrusion is not uniformly distributed throughout the tendon rim region; and (5) the long-diffusion-time ADC behavior is consistent with the T1 spin editing hypothesis of the spectroscopic work. From the clinical fMRI studies, an analysis method was presented for observing dynamic changes in brain regions involved in different neural network processes during a period of sustained activity. The results from these studies are consistent with the idea that over time, brain regions adapt to the given task demands through either recruitment or discharge of adjacent areas of tissue. These results also indicate that traditional analysis of block design fMRI studies may underestimate dynamic changes in brain regions during a sustained task. The analysis method may be useful as an exploratory tool to observe region specific variations in activation that may allow inferences to be made regarding how different brain regions adapt to and interact with one another during periods of extended activity.

With conventional oil reserves in decline, energy companies are increasingly turning to enhanced oil recovery (EOR) processes to extend the productive life of oilfield wells. Laboratory-scale core floods, in which one fluid displaces another from the pore space of a rock core, are widely used in petroleum research for oilfield evaluation and screening EOR processes. Achieving both macro- and pore-scale understandings of such fluid displacement processes is central to being able to optimise EOR strategies. Many of the mechanisms at play, however, are still poorly understood. In this thesis nuclear magnetic resonance (NMR) has been used for quantitatively, non-invasively and dynamically studying laboratory core floods at reservoir-representative conditions. Spatially-resolved relaxation time measurements (L-T1-T2) have been applied to studying a special core analysis laboratory (SCAL) protocol, used for simulating reservoir oil saturations following initial oil migration (primary drainage) and characterising core samples (capillary pressure curves). Axial heterogeneities in pore filling processes were revealed. It was demonstrated that upon approaching irreducible water saturation, brine saturation was reduced to a continuous water-wetting film throughout the pore space; further hydrocarbon injection resulted in pore pressure rise and wetting film thinning. L-T1-T2 techniques were also applied to a xanthan gum polymer-EOR flood in a sandstone core, providing a continuous measurement of core saturation and pore filling behaviours. A total recovery of 56.1% of the original oil in place (OOIP) was achieved, of which 4.9% was from xanthan. It was demonstrated that deposition of xanthan debris in small pores resulted in small-pore blocking, diverting brine to larger pores, enabling greater oil displacement therein. L-T1-T2, spectral and pulsed field gradient (PFG) approaches were applied to a hydrolysed polyacrylamide (HPAM)-EOR flood in a sandstone core. A total recovery of 62.4% of OOIP was achieved, of which 4.3% was from HPAM. Continued brine injection following conventional recovery (waterflooding) and EOR procedures demonstrated most moveable fluid saturation pertained to brine, with a small fraction to hydrocarbon. Increases in residual oil ganglia size was demonstrated following HPAM-EOR, suggesting HPAM encourages ganglia coalescence, supporting the "oil thread/column stabilisation" mechanism proposed in the literature. NMR relaxometry techniques used for assessing surface interaction strengths (T1/T¬2) were benchmarked against an industry-standard SCAL wettability measurement (Amott-Harvey) on a water-wet sandstone at magnetic field strengths comparable to reservoir well-logging tools (WLTs). At 2 MHz, T1/T2 was demonstrated to be weakly sensitive to the core wettability, although yielded wettability information at premature stages of the Amott-Harvey cycle. This suggests the potential for NMR to deliver faster wettability measurements, in SCAL applications or downhole WLT in situ reservoir characterisation.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Includes bibliographical references. / by William Paul Rothwell. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1979. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / Ph.D.

Neste trabalho foram estudados novos eletrólitos poliméricos e vidros fosfatos utilizando a técnica de Ressonância Magnética Nuclear. Os eletrólitos estudados foram o poliéster (etileno glicol / ácido cítrico - EG/AC) e os filmes de hidroxietilcelulose (HEC) entrecruzados com diisocianatos de poli (óxido de etileno) e poli (óxido de propileno), ambos dopados com sais de lítio No estudo dos eletrólitos poliméricos, foram realizadas medidas da forma de linha e da taxa de relaxação spin-rede do 1H e do 7Li em função da temperatura e da viscosidade, com objetivo de estudar a mobilidade da cadeia polimérica e dos íons lítio. Os valores para o tempo de correlação, obtidos dos dados de relaxação, mostram que a mobilidade da cadeia polimérica e dos íons lítio são comparáveis aos encontrados em outros eletrólitos poliméricos similares Os sistemas vítreos estudados foram o vidro fosfato In(PO3)3 e o sistema binário (1-x)In(PO3)3 - xBaF2, com o objetivo de determinar o grau de polimerização da cadeia de fosfatos. Os estudos do 31P MAS RMN para diferentes tempos de fusão dos vidros fosfatos, permitiram verificar que presença da água reduz o comprimento da cadeia pela hidrólise das ligações P-O-P produzindo duas cadeias com grupos terminais -P-OH. A adição do BaF2 no vidro fosfato, reduz o comprimento da cadeia de fosfatos formando oxigênio não ponteante. Altas concentrações do BaF2 causa a depolimerização da cadeia de fosfatos formando grupos pirofosfatos (Q1) e grupos ortofosfatos (Q0). / In this work we report the study of new polymer electrolytes and phosphate glasses using Nuclear Magnetic Resonance (NMR) technique. The polymer electrolytes studied were polyester (glycol ethylene / citric acid) and films formed by hydroxyethylcelluloses (HEC), poly(ethy1ene oxide) and poly(propy1ene oxide) diisocyanates, both with lithium salt. To study the mobility of polymer chains and lithium ions in the polymer electrolytes, measurements of the temperature and viscosity dependence of 1H e do 7Li lineshape and spin-lattice relaxation rate were realized. The correlation times obtained from relaxation data, show that the mobility of polymer chains and lithium ions are comparable to those found in other similar polymer electrolytes. The degree of polymerization of the phosphate chain was studied in phosphate glass In(PO3)3 and in the binary system(1-x)In(PO3)3 - xBaF2. The 31P MAS NMR for different melting times, indicate that the water reduces the chain length by hydrolyzing P-O-P bonds to produce two separated chains, terminated by -P-OH groups. The addition of BaF2 in the phosphate glass, reduces the phosphate chain length by forming non-bridging oxygen ions. High concentration of BaF2 causes depolymerization of the phosphate chain to create pyrophosphate groups (Q1) and orthophosphate groups (Q0).

Nesta dissertação apresentaremos um estudo da adiabaticidade em Ressonância Magnética Nuclear. Para tal, apresentaremos inicialmente uma revisão sobre o conceito de adiabaticidade em sistemas quânticos fechados e abertos. Muitos processos adiabáticos comumente utilizados em Ressonância Magnética apresentam um bom desempenho, embora a aproximação adiabática não seja valida durante todo o processo, então através do formalismo da superadiabaticidade de Berry faremos correções para que o pulso satisfaça a condição adiabática. Nesta abordagem, um Hamiltoniano dependente do tempo e que evolui lentamente é iterativamente transformado em quadros diagonais dependentes do tempo até que a aproximação adiabática mais precisa é obtida. Examinaremos as capacidades das iterações super-adiabáticas para produzir uma sequência de atalhos para a adiabaticidade do sistema e estenderemos o conceito da dinâmica superadiabática para sistemas abertos, cuja evolução é governada por uma equação mestra na forma de Lindblad, fornecendo o quadro geral necessário para determinar a estratégia de controle necessário para alcançar a superadiabaticidade. / We present a study of adiabaticity in Nuclear Magnetic Resonance. First, we present a review on the concept of adiabaticity in closed and open quantum systems. Many commonly used adiabatic processes in Magnetic Resonance perform well even though the adiabatic approximation does not appear to hold throughout the process, then through the use Berry\'s superadiabatic formalism make corrections to the pulse satis_es the adiabatic condition. This approach, a but time-dependent Hamiltonian slowly evolving is iteratively transformed into time-dependent diagonal frames until the most accurate adiabatic approximation is obtained. Examine the capabilities of superadiabatics iterations to produce a shortcut sequence to adiabaticity system and extend the concept of dynamic superadiabatic for open systems, whose evolution is governed by a master equation of Lindblad form, providing the necessary framework to determine the strategy control needed to achieve superadibaticity.

No description available.