Dissertations / Theses on the topic 'Proton magnetic resonance spectroscopy'

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1

Gill, Simrandip Kaur. "Single voxel proton magnetic resonance spectroscopy of childhood brain tumours." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4899/.

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Conventional magnetic resonance imaging (MRI) is essential for the management of childhood brain tumours. However, it is increasingly being supplemented with functional techniques such as magnetic resonance spectroscopy (MRS). This thesis investigates how pre-treatment single voxel MRS can aid in diagnosis and surveillance of paediatric brain tumours and identify prognostic biomarkers. Data from multiple centres, scanners from three leading manufacturers and field strengths of 1.5 T and 3 T are incorporated. MRS was analysed using TARQUIN software with metabolite peaks fitted using a simulated basis set to provide metabolite concentrations. Univariate and multivariate statistical tests were used to compare variables. Multi-scanner spectroscopy detected significant differences in common and rare paediatric brain tumours. Diagnostic metabolite profiles were able to confirm tumour on follow-up imaging. Elevated creatine and total choline determined good prognosis in medulloblastoma. Myo-inositol and citrate aided in the characterisation of diffuse pontine gliomas (DIPG). While conventional MRI was unable to identify prognostic markers for DIPG, elevated taurine was found to be significantly associated with a better prognosis. The results encourage the use of MRS as an adjunct to conventional MRI in routine clinical practice. For future studies, accurate assignment of biomarkers will be determined in tumour tissue using in vitro high-resolution spectroscopy methods.
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2

Meng, Jiqun J. "Line scan proton magnetic resonance spectroscopic imaging." Thesis, Massachusetts Institute of Technology, 1995. http://hdl.handle.net/1721.1/36963.

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3

Potwarka, John J. "A proton decoupled phosphorus-31 nuclear magnetic resonance spectroscopy study of schizophrenia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0019/MQ58006.pdf.

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4

Fellows, Greg A. "Proton magnetic resonance spectroscopy (1H-MRS) and transcriptional analysis of brain tumours." Thesis, St George's, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546778.

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5

D'Souza, Patricia Christina. "Quantitation of brain metabolite concentrations and temperature by proton magnetic resonance spectroscopy." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265011.

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6

Rial, Franco B. "Development of proton magnetic resonance spectroscopy in human heart at 3 Tesla." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:48e60f2d-ec5c-4b20-999a-b726f8baa436.

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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.
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7

Cobbold, Jeremy Francis Lars. "Imaging techniques in chronic liver disease : applications of proton magnetic resonance spectroscopy." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/11263.

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8

Davidson, Anne. "Investigation of treatment related neurotoxicity following childhood cancer by proton magnetic resonance spectroscopy." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287842.

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9

Wild, James Michael. "Proton magnetic resonance spectroscopic imaging of the human brain." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/22742.

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Over the last ten years proton NMR spectroscopy has been performed on clinical MRI scanners using single voxel localisation and spectroscopic imaging sequences. In this work inner volume excitation of a transverse imaging plane within the brain has been used to obtain single slice spectroscopic images of proton metabolites. The existing image processing protocols used to construct the metabolite images were improved and optimised so as to give as accurate a picture of metabolite distribution as possible. Inaccuracy in these images can be introduced by the excitation profile of the radio frequency pulses used in inner volume excitation. A new normalisation technique is proposed which will remove these inaccuracies enabling more reliable quantification of metabolite concentrations. Of particular importance in stroke is the metabolite lactate, elevated levels of which are symptomatic with the conditions of anaerobic glycolysis that are thought to precede infarction. The signal from lactate is often obscured by lipid and macro-molecule resonances in the same frequency range. Lactate editing sequences compatible with the hardware capabilities of the scanner and spectroscopic imaging sequences were investigated for viability in-vivo. Using two different editing sequences lactate editing was performed successfully in vitro and in vivo. In-vivo results are presented from a study of 40 stroke patients and a smaller pilot study of 8 head injury patients. These patients were drawn from the Lothian Stroke Register as part of the Clinical Research Initiative (CRI) in stroke and head injury being co-ordinated at the Western General Hospital, Edinburgh. To our knowledge this is the largest proton spectroscopic study of acute stroke patients and as such should have a significant bearing in analysing the physiological implications of the disease.
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10

Lee, Kai Mon. "Solution structures of yeast ribosomal 5S and 5.8S ribonucleic acids via 500 MHz proton nuclear magnetic resonance spectroscopy /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487322984316599.

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11

Tan, Peuen Clara. "Evaluation of proton magnetic resonance spectroscopy in predicting treatment response of malignant breast lesions." Thesis, University of Hull, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440130.

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12

Naude, Natali. "Proton magnetic resonance spectroscopy to evaluate in vivo breast tissue chemistry at 3.0 Tesla." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/225943/1/Natali_Naude_Thesis.pdf.

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The research utilised in vivo 2D magnetic resonance spectroscopy in conjunction with standard breast MRI to investigate MR-visible characteristics associated with breast density and menopausal status. Statistically significant differences were recorded in various neutral lipids and metabolites, and with further development, may enable non-contrast MRI to evaluate breast cancer risk, avoiding the use of gadolinium-based contrast media. The tentative assignment of methylmalonic acid (MMA), which has been associated with cancer proliferation, was also made. Another spectral region was identified relating to polyunsaturated fatty acid content in breast tissue. PUFAs have been shown to have a protective effect against breast cancer.
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13

Mumuni, Abdul Nashirudeen. "Investigation of brain tissue water NMR response by optimised quantitative single-voxel proton magnetic resonance spectroscopy." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4717/.

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Nuclear Magnetic Resonance (NMR) is a phenomenon in which certain nuclei in the presence of a magnetic field and radiofrequency (RF) radiation emit a certain amount of signal at a frequency equal to that of the RF radiation. Proton Magnetic Resonance Spectroscopy (1H-MRS) is an NMR technique capable of measuring the chemical composition, often referred to as metabolites, of the human body non-invasively and in vivo. It is commonly used as a research tool in the investigation of neurological disorders such as multiple sclerosis, brain tumors, stroke, clinical depression, and schizophrenia. Accurate quantification of the metabolites of interest requires a reference standard of known and fixed concentration. Brain tissue water has been previously reported to have a fairly constant and known concentration, and so has been suggested to be a suitable reference concentration in absolute quantitative 1H-MRS of the human brain. In practice, however, it is challenging to measure the actual tissue water concentration; hence, some studies choose to use estimates of tissue water concentration from the literature. These literature values are usually averages from a healthy study group. There are however indications that brain tissue water content could vary widely in certain disease conditions such as in brain tumors and inflammation. In such situations, absolute metabolite quantification using the literature estimates of tissue water content will be inaccurate while the measurement of cerebral water content using the available techniques will be impractical for the patients due to scanning time considerations. It is therefore necessary to develop a technique that can be used to quantify both the reference water and metabolite concentrations, simultaneously without subject tolerance issues. The main objective of this thesis was to investigate the response of water NMR signal from human brain tissue under various measurement conditions using the single-voxel 1H-MRS technique. As part of the investigation, the thesis also focused on the development of methods for the absolute quantification of cerebral water and metabolite concentrations. A standard 1H-MRS water-suppressed acquisition on the General Electric (GE) MR scanner acquires some unsuppressed-water spectra at the beginning of the PRESS pulse sequence. Using the Spectroscopy Analysis by GE (SAGE) software package (version 7), this thesis developed methods to optimise the unsuppressed-water and suppressed-water signals from which, respectively, cerebral water and metabolite concentrations were estimated. The unsuppressed-water signal response characteristics were investigated in experiments at 3 T that involved: 1) variation of the MRS voxel position over a three-dimensional RF field within an eight-channel head coil; 2) measurement of the relaxation times of brain tissue water using standard saturation recovery and multi spin-echo MRS techniques; 3) measurement of brain tissue water content in peripheral inflammation; and 4) estimation of the BOLD effect on the water spectral peak. The stability of the MR scanner used for all the investigations was assessed. Over the project period, the worst precision measurements of the scanner (for both water and metabolite signals) were observed to be about 12 % and 26 % in serial phantom and human studies, respectively. The MRI/MRS scanner was therefore found to measure water and metabolite signals with good precision, both in vivo and in vitro. By recording the water NMR signal responses at various locations within the phased-array head coil, RF sensitivity profile (voxel position-dependent) equations of the head coil were obtained. The coordinates of any in vivo voxel could be substituted into an appropriate profile equation to estimate an unsuppressed-water signal area that could be used as a reference signal to quantify brain tissue water content. This novel technique of quantifying cerebral water content is superior to the previous techniques of performing multi-echo unsuppressed-water signal acquisitions. The method does not require extra unsuppressed-water acquisitions, or corrections for variations in the sensitivity of the eight-channel head coil as both the in vivo and reference signals are acquired from the same voxel position. Brain tissue water content was subsequently quantified accurately using the newly developed method of referencing. In frontal brain voxels, the average water content, WC of grey matter, GM was found to be higher than that of white matter, WM (GM/WM WC ± SE = 46.37 ± 2.58/42.86 ± 2.46 mol/kg; p = 0.02); parietal voxels also showed a similar comparison (GM/WM WC ± SE = 37.23 ± 1.70/34.14 ± 2.02 mol/kg; p = 0.03). These findings were consistent with previous reports of cerebral water content. For regions of mixed proportions of grey and white matter tissues, the average water contents of each tissue type considered separately (by voxel segmentation) and together were found to compare with literature estimates. Using data from five voxel positions, average brain tissue water content was observed to be uniformly distributed across the human brain by one-way ANOVA (p = 0.60), and did not vary significantly with gender (p > 0.05) and age (p > 0.05). For the first time, cerebral water content was observed in this thesis to remain fairly constant in psoriatic arthritis, a peripheral inflammatory condition (one-way ANOVA, p = 0.63). Among five brain metabolites quantified in the psoriasis patients, only the mean concentration of creatine, Cr was found to be significantly lower in the frontal grey matter voxels of the patients, PsA compared to healthy controls, HC at baseline (PsA/HC ± SE = 6.34 ± 0.38/7.78 ± 0.38 mM/kg; p = 0.01) and post-TNF-alpha blockade medication (PsA/HC ± SE = 6.69 ± 0.25/7.78 ± 0.38 mM/kg; p = 0.03). None of the metabolite concentrations, including Cr (p = 0.27), changed significantly with medication. The condition of PsA was not observed to affect the mood of the patients, as indicated by their BDI scores. The significant finding of Cr concentration alteration in psoriatic arthritis thus suggests that Cr may not be a reliable denominator in studies of psoriasis that express the metabolite levels as ratios. The T1 and T2 relaxation times of water and the metabolites were measured in the prefrontal grey matter (T1/T2 ± SE = 1574 ± 61/147 ± 6 ms) and bilateral Hippocampi (T1/T2 ± SE; left = 1475 ± 68/178 ± 83 ms, right = 1389 ± 58/273 ± 98 ms). The relaxation time estimates for the metabolites were in agreement with literature values; relaxation times for water however were measured for the first time in those regions and at 3 T. The measured relaxation times were used to correct the water and metabolite signals for relaxation effects during their absolute quantification, and could as well serve the same purpose in future studies. There is increasing interest in the BOLD response of cerebral metabolites and water during tasks. This thesis thus also assessed changes in brain tissue metabolite and water contents while a subject experienced a visual stimulus. In the presence of the visual stimulus, the BOLD effects on the metabolite and water spectral peaks were found to be comparable, as has been observed in previous studies. For the first time, this thesis further investigated the impact of temporal resolution (determined by NEX) on the amount of the BOLD signal acquired from cerebral water and metabolites. In a single visual activation paradigm, the BOLD effect resulted in increased water peak area which differed significantly between NEX values of 2 and 8 (p < 0.01); this observation also was true for NAA and Glu. The findings thus suggest that temporal resolution of the MRS data could result in significant differences in the results of functional MRS studies.
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14

Kim, Jong Hwa. "Bacillus megaterium ribosomal 5S RNA structure from proton nuclear magnetic resonance spectroscopy and molecular dynamics simulations /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487683049376233.

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15

Choi, Seongjin. "Proton NMR and MRI studies of sub-millimeter sized biological objects." Columbus, Ohio : Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1204559010.

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16

Lee, Shen-Han. "¹H magnetic resonance spectroscopic imaging of tumour extracellular pH : the role of carbonic anhydrase IX." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607910.

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17

Luo, Ying. "Heme Proton Resonance Assignments and Kinetics Study in High-spin and Mixed-spin Metmyoglobin Complexes by Chemical Exchange NMR Spectroscopy." PDXScholar, 1996. https://pdxscholar.library.pdx.edu/open_access_etds/5238.

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NMR studies of paramagnetic hemoproteins have improved significantly our understanding of the structure-function relationship ofhemoproteins in general. Up to date most of the studies focus on low-spin ferric systems which are characterized by relatively narrow resonance peaks and concomitant better resolution. However, characterizing in detail the NMR spectra of high-spin ferric hemoproteins is important since there are several hemoproteins, such as peroxidases, catalases, oxygenases, and some ferricytochromes that contain high-spin iron (III) in their biologically active forms. Yet assigning resonances from heme peripheral protons and/or heme pocket residues in high-spin myoglobins is a daunting undertaking. Only a sparse number of active site residues are assigned in such instances, even for metaquo-myoglobin. The protons from the heme and heme pocket residues in high-spin complexes experience extremely fast relaxation and very broad linewidths, which impede the 2D methods that detect through-space and through-bond connectivities. It is the intention of this study to develop an effective strategy to gain more resonance assignments for fast-relaxing protons in hemoproteins. We have set out to use a combined strategy, using two-dimensional exchange spectroscopy (2D-EXSY) with two dimensional nuclear Overhauser effect spectroscopy I correlation spectroscopy I total correlation spectroscopy (NOESY/COSY/TOCSY). I demonstrate here that 2D EXSY experiments can be used to obtain assignment correlations for the heme protons of methydroxy-, metthiocyano-, metaquo-, and metimidazole-myoglobin forms. All these assignments are unambiguous and straightforward. Moreover, saturation-transfer experiments allow determination of ligand binding kinetics. Thus, the exchange rates between the metaquo- and metimidazole- or methyl substituted imidazole myoglobin complexes are estimated. The differences between the exchange rates reflect the differences in the hydrophobic and steric interactions between the ligands and the protein moiety. Although I only demonstrate the feasibility of2D EXSY for the myoglobin case, this assignment strategy should to be applicable to other hemoprotein systems.
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18

Prescott, Andrew Paul. "The development and application of localised two-dimensional proton magnetic resonance spectroscopy for clinical investigation in humans." Thesis, Institute of Cancer Research (University Of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405948.

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19

Mei, Chang-Sheng. "Accelerated MR Thermometry for High Intensity Focused Ultrasound Therapy." Thesis, Boston College, 2011. http://hdl.handle.net/2345/2425.

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Thesis advisor: Michael Graf
The purpose of this dissertation was to investigate the temporal limit on the ability to measure temperature changes using magnetic resonance imaging (MRI). The limit was examined in experiments using a variety of imaging techniques for MRI-based temperature measurements. We applied these methods for monitoring temperature changes in focused ultrasound (FUS) heating experiments. FUS is an attractive alternative to surgical resection due to its noninvasive character. FUS treatments have been successfully conducted in several clinical applications. MRI and MR thermometry is a natural choice for the guidance of FUS surgeries, given its ability to visualize, monitor, and evaluate the success of treatments. MR thermometry, however, can be a very challenging application, as good resolution is often needed along spatial, temporal as well as temperature axes. These three quantities are strictly related to each other, and normally it is theoretically impossible to simultaneously achieve high resolutions for all axes. In this dissertation, techniques were developed to achieve this at cost of some reduction in spatial coverage. Given that the heated foci produced during thermal therapies are typically much smaller than the anatomy being imaged, much of the imaged field-of-view is not actually being heated and may not require temperature monitoring. By sacrificing some of the in-plane spatial coverage outside the region-of-interest (ROI), significant gains can be obtained in terms of temporal resolution. In the extreme, an ROI can be chosen to be a narrow pencil-like column, and a sampling time for temperature imaging is possible with a temporal resolution of a few milliseconds. MRI-based thermal imaging, which maps temperature-induced changes in the proton resonance frequency, was implemented in two projects. In the first project, three previously described, fast MR imaging techniques were combined in a hybrid method to significantly speed up acquisition compared to the conventional thermometry. Acceleration factors up to 24-fold were obtained, and a temporal resolution as high as 320 milliseconds was achieved. The method was tested in a gel phantom and in bovine muscle samples in FUS heating experiments. The robustness of the hybrid method with respect to the cancellation of the fat signal, which causes temperature errors, and the incorporation of the method into an ultrafast, three dimensional sequence were also investigated. In the second project, a novel MR spectroscopic sequence was investigated for ultrafast one-dimension thermometry. Temperature monitoring was examined during FUS sonications in a gel phantom, SNR performance was evaluated in vivo in a rabbit brain, and feasibility was tested in a human heart. It was shown capable in a FUS heating experiment in a gel phantom of increasing temporal resolution to as high as 53 milliseconds in a three Tesla MRI. The temporal resolution achieved is an order of magnitude faster than any other rapid MR thermometry sequences reported. With this one-dimensional approach, a short sampling time as low as 3.6 milliseconds was theoretically achievable. However, given the SNR that could be achieved and the limited heating induced by FUS in the gel phantom in a few milliseconds, any temperature changes in such a short period were obscured by noise. We have analyzed the conditions whereby a temporal resolution of a few-milliseconds could be obtained
Thesis (PhD) — Boston College, 2011
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Physics
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20

Fairbrother, Wayne J. "Phosphate interactions with proteins." Thesis, University of Oxford, 1989. http://ora.ox.ac.uk/objects/uuid:f4aa96db-9e7c-4a18-a859-de0d90080f4f.

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Proton nuclear magnetic resonance (NMR) spectroscopy has been used to investigate the interaction of yeast phosphoglycerate kinase (PGK) with its phosphate containing substrates, ATP and 3-phosphoglycerate (3-PG). The application of one-dimensional and, for the first time, two-dimensional proton NMR techniques to this large protein has enabled specific resonance assignments to be made. Assignment has been aided by the investigation of specifically deuterated protein and site-specific mutant forms of the protein, including the isolated N- and C-domains. The effects of ATP and 3-PG binding on the proton NMR spectrum of yeast PGK have been characterised and the assigned resonances used as local probes of structural and dynamic changes. Two binding sites have been determined for the nucleotide substrate, ATP, the occupancies of which are dependent on Mg2+ concentration. One site corresponds to the catalytic site determined crystallographically. A single binding site was found for 3-PG. This binding was shown to cause highly specific conformational changes throughout the N-domain and the interdomain region, which involve the relative movement of at least three α-helices. Investigation of 3-PG binding to several site-specific mutant forms of yeast PGK revealed a critical role for arginine 168 in the propagation of these changes. The general binding of anions to yeast PGK was investigated using the paramagnetic probes [Cr(CN)6]3- and [Fe(CN)6]3-, and the diamagnetic anion [Co(CN)6]3-. The primary anion binding site was determined from [Cr(CN)6]3- broadening data and found to share some side-chains involved in 3-PG binding, namely histidine 62 and arginine 168. Evidence for a secondary anion site was found. The anion binding data is discussed in view of the complex activation/inhibition effects of anions on the catalytic activity. Investigation of the isolated N- and C-domains showed that both can fold independently and confirmed that the C-domain is a nucleotide binding domain. It appears that the presence of the interdomain residues and/or the C-terminal peptide are necessary for 3-PG binding to the N-domain. This work shows that the specificity of the substrates is in binding, as expected, but also in the motions induced in the protein as a whole.
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21

Veale, Margaret Fiona. "Activated immune cells : 1H-NMR spectroscopy and flow cytometry studies." Thesis, The University of Sydney, 1996. https://hdl.handle.net/2123/27547.

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Proton nuclear magnetic resonance (lH-NMR) spectroscopy has been used to study immune cell activation. One-dimensional and two—dimensional 1H-NMR spectra of activated immune cells are dominated by signals arising from elevated levels of isotropically tumbling (ie., NMR-visible) mobile lipid. An increase in the level of mobile lipid compared with that seen in resting cells has been observed in a variety of activated immune cells. The appearance of the mobile lipid is associated with activation and can be induced by a variety of stimuli. However, the origin and function of the neutral lipid resonances in 1H-NMR spectra of activated immune and other cell types has been unresolved. I propose that the mobile lipids arise from phosphatidylcholine (PC) cycling.
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22

Ross, Amy Psychiatry Faculty of Medicine UNSW. "Longitudinal study of cognitive and functional brain changes in ageing and cerebrovascular disease, using proton magnetic resonance spectroscopy." Awarded by:University of New South Wales. School of Psychiatry, 2005. http://handle.unsw.edu.au/1959.4/27329.

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The neurophysiological basis of cognition changes with age is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event related potentials, brain size and cerebral blood flow. Proton magnetic resonance spectroscopy (1H-MRS) is an in vivo method used to detect metabolites within the brain that are relevant to certain brain processes. Recent studies have shown that these metabolites, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in patients with a variety of cognitive disorders associated with ageing and in normal ageing subjects. We have studied the relationship between metabolites and cognitive function in elderly patients 3 months and 3 years after a stroke or transient ischemic attack (TIA) and in an ageing comparison group. Metabolites were no different between stroke/TIA patients and elderly controls, however, there were significant metabolite differences between stroke/TIA patients with cognitive impairment (Vascular Cognitive Impairment and Vascular Dementia) and those without. Frontal measures of NAA and NAA/Cr predicted cognitive decline over 12 months and 3 years in stroke/TIA patients and elderly controls, and these measures were superior predictors than structural MRI measures. Longitudinal stability of metabolites in ageing over 3 years was associated with stability of cognitive function. The results indicate that 1H-MRS is a useful tool in differentiating stroke/TIA patients with and without cognitive impairment, with possibly superior predictive ability than structural MRI for assessing future cognitive decline. The changes in 1H-MRS that occur with ageing and cognitive decline have implications for the neurophysiological mechanisms and processes that are occurring in the brain, as well as application to clinical diagnosis, the early detection of pathology and the examination of longitudinal change.
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Olszewska, Agnieszka [Verfasser]. "Interictal single-voxel 1H-proton magnetic resonance spectroscopy of the temporal lobe in dogs with idiopathic epilepsy / Agnieszka Olszewska." Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1182893287/34.

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24

Lindskog, Magnus. "Tumor lipid status and the responses to therapy in neuroblastoma : with emphasis on treatment monitoring by proton magnetic resonance spectroscopy /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-160-1/.

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Baker, Ross E. "The time course of changes in skeletal muscle metabolites during muscle repair, as detected by proton nuclear magnetic resonance spectroscopy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0002/MQ41678.pdf.

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26

Fievisohn, Elizabeth Mary. "Traumatic Brain Injury Mechanisms in the Gottingen Minipig in Response to Two Unique Input Modes." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/64280.

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Traumatic brain injury (TBI) continues to be a widespread problem in the United States with approximately 1.7 million occurrences annually [1]. Current automotive crash test standards use the Head Injury Criterion (HIC) [2] to assess head injury potential, but this metric does not relate an impact to underlying damage. For an injury metric to effectively predict TBI, it is crucial to relate level of impact to resulting injury. The research presented in this dissertation explains the development and repeatability of two novel injury devices, impact response characterization over the course of 24 hours in the Gottingen minipig and the relationships between metabolite changes, underlying disruption, and impact kinematics, and the characterization of impact response over the course of 72 hours. The translation-input and combined translation and rotation-input injury devices were shown to be repeatable, minimizing the number of animals needed for testing. Impact response over the course of 24 hours showed axonal disruption through immunostaining and proton magnetic resonance spectroscopy. The translation-input injury group metabolite analyses revealed the initial stages of glutamate excitotoxicity while the combined-input injury group showed a clear pathway for glutamate excitotoxicity. Numerous correlative relationships and potential underlying disruption predictors were found between metabolites, immunostaining, and kinematics. The most promising predictor combination for the translation-input injury device was N-acetylaspartylglutamate/Scyllo at 24 hours compared to 1 hour and linear speed for predicting underlying light neurofilament disruption. For the combined-input injury device, the strongest predictor combination was Glutamine/N-acetylaspartylglutamate at 24 hours compared to baseline and angular acceleration for predicting underlying light neurofilament disruption. Statistically significant predictors were found between Glutamate+Glutamine/Total Creatine at 24 hours compared to baseline and all kinematics and injury metrics with an angular component for predicting heavy neurofilament disruption. Analyses over the course of 72 hours revealed persistent axonal disruption and metabolite perturbations. Overall, this dissertation and the complementary parts of this project have many societal implications. Due to the high incidence of traumatic brain injury, there is a need for prevention, mitigation, and treatment strategies. Developing a new injury metric will help improve prevention strategies, especially in the automotive, sporting, and military environments. 1 Faul, M., Xu, L., Wald, M. M., and Coronado, V. G. (2010). Traumatic Brain Injury in the United States. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 2 Versace, J. (1971). A Review of the Severity Index. SAE Technical Paper. No. 710881
Ph. D.
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27

Faraj, Achraf Al. "Biodistribution and biological impact of nanoparticles using multimodality imaging techniques : (Magnetic resonance imaging)." Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00696221.

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As novel engineered nanoparticles such as single-walled carbon nanotubes (SWCNT) are extensively used in nanotechnology due to their superior properties, it becomes critical to fully understand their biodistribution and effect when accidently inhaled. There fore, development of animaging technique which allow longitudinal in vivo follow-up of SWCNT effect based on their intrinsic properties is highly desirable. Non invasive free-breathing hyperpolarized 3He lung MRI protocol was developed complementary to proton systemic MR protocol to allow monitoring SWCNT based on their intrinsic iron impurities after intrapulmonary exposition. Combined toproton lung MRI and ex vivo optical and electron microscopy at different time points, this protocol represents a powerful multimodality imaging techniques which allows a full characterization of the biodistribution and biological impacts of iron containing SWCNT. SWCNT was found to produce granulomatous and inflammatory reactions in a time and dose dependent manner with their bio persistenc eafter intrapulmonary exposition.From biological impact evaluations after intrapulmonary exposition towards biomedical applications, SWCNT hold promise for applications in nanomedicine field with their distinct architecture and their novel physicochemical properties. The biodistribution and pharmacological profile of various well-dispersed pristine and functionalized SWCNT were assessed in blood and target tissues after their intra venous administration by longitudinal in vivo susceptibility weighted MRI and their potential effect on liver metabolism by ex vivo HRMAS 1H NMR. No presence ofacute toxicological effect (variation in liver metabolism) was observed confirmed by the absence of clustering in NMR spectra using Principal Component Analysis (specific biomarkers of toxicity).
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Giapitzakis, Ioannis-Angelos [Verfasser], and Anke [Akademischer Betreuer] Henning. "Single-Voxel Proton Magnetic Resonance Spectroscopy in the Human Brain at 9.4 T : Methods and Applications / Ioannis-Angelos Giapitzakis ; Betreuer: Anke Henning." Tübingen : Universitätsbibliothek Tübingen, 2018. http://d-nb.info/1168634512/34.

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Giapitzakis, Ioannis-Angelos I. [Verfasser], and Anke [Akademischer Betreuer] Henning. "Single-Voxel Proton Magnetic Resonance Spectroscopy in the Human Brain at 9.4 T : Methods and Applications / Ioannis-Angelos Giapitzakis ; Betreuer: Anke Henning." Tübingen : Universitätsbibliothek Tübingen, 2018. http://d-nb.info/1168634512/34.

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Brief, Elana Esther. "Proton magnetic resonance spectroscopy of human brain, T¦1 and T¦2 relaxation and absolute concentrations of metabolites in patients and healthy volunteers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0016/NQ56509.pdf.

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Story, Lisa. "Volumetric blood flow and assessment of the metabolic profile of the developing brain in growth restricted fetuses : an ultrasound and proton magnetic resonance spectroscopy study." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9098.

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Introduction Intrauterine growth restriction (IUGR) is a common obstetric condition causing significant perinatal morbidity and mortality. A phenomenon known as brain sparing occurs in IUGR fetuses whereby blood is preferentially diverted to supply the developing brain often at the expense of other organs. However, although this supposedly neuroprotective mechanism exists, children that were growth restricted in utero have a higher incidence of long term neurodevelopmental sequelae. This thesis therefore aims to explore the brain redistribution phenomenon in detail by investigating cerebral volume blood flow and the metabolic profile of the IUGR brain using high resolution ultrasound and proton magnetic resonance spectroscopy respectively. Methods 150 appropriately grown and 78 IUGR fetuses had volume blood flow assessed longitudinally using high resolution ultrasound and power Doppler in multiple fetal vessels. The metabolic status of the brain was then assessed in 46 appropriately grown and 26 growth restricted fetuses using Proton Magnetic Resonance Spectroscopy. Results IUGR fetuses had a generalised increase in vessel diameter in comparison with appropriately grown control fetuses, and when standardised for weight, increased volume blood flow was noted in the middle cerebral, renal, umbilical and carotid arteries and the ascending aorta. No difference in flow was noted in the descending aorta. N-acetylaspartate:Choline and N-acetylaspartate:Creatine ratios were reduced in IUGR fetuses and lactate was present in the developing brains of both appropriately grown and growth restricted fetuses. Conclusions Volume blood flow is significantly altered in IUGR fetuses, likely to be mediated by alterations in vessel diameter. This may be secondary to alterations in circulating vasoactive factors or as a result in alterations of the composition of vessel walls. The metabolic status of the brain tissue is also altered which may in part explain the higher incidence of neurodevelopmental sequelae in some fetuses that were growth restricted in utero.
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Bruylants, Gilles. "Etude par calorimétrie à titrage isotherme (ITC) et spectroscopie de résonnance magnétique nucléaire (RMN) des effets de protonation liés à l'interaction entre l'alpha-chymotrypsine et la proflavine / Gilles Bruylants." Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210977.

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Le nombre de cibles potentielles pour la conception de nouvelles molécules à activité thérapeutique ne cesse de croître. Pour chaque cible, il est nécessaire d’identifier des molécules actives et de les optimiser afin d’atteindre l’affinité et la sélectivité recherchées. Ces nouveaux défis accentuent la nécessité d’améliorer notre compréhension des facteurs qui mènent à la reconnaissance moléculaire entre une drogue potentielle et une macromolécule biologique, et particulièrement des facteurs énergétiques à la base de la stabilisation d’un complexe d’interaction. Dans le cadre de ce travail, nous nous sommes intéressés à l’effet que pouvaient avoir les équilibres de protonation/déprotonation des résidus ionisables d’une protéine sur les paramètres thermodynamiques caractérisant la complexation d’un ligand. Dasns ce but, nous avons étudié l’interaction entre l’α-chymotrypsine et un de ses inhibiteurs compétitifs, la proflavine. Cette protéine est représentative d’un nombre important d’enzymes présentant le même mécanisme catalytique. La compréhension des facteurs qui régissent les équilibres de protonation/déprotonation des résidus ionisables présents dans son site actif ainsi que de l’effet sur ceux-ci de l’interaction avec des ligands est d’une importance primordiale pour le développement d’inhibiteurs plus sélectifs de ces protéases.

Cette étude s’est essentiellement composée de trois volets. (i) La réalisation d’un modèle du complexe d’interaction afin de confronter des données structurales aux données expérimentales recueillies. (ii) L’étude de l’interaction entre l’α-chymotrypsine et la proflavine par spectroscopie de Résonance Magnétique Nucléaire (RMN) afin de mettre en évidence les résidus ionisables dont les équilibres de protonation/déprotonation sont influencés par la complexation du ligand. (iii) L’étude de la thermodynamique de l’interaction par Calorimétrie à Titrage Isotherme (ITC) et spectroscopie d’absorption en fonction de l’état d’ionisation des résidus identifiés par l’étude RMN.

Le modèle du complexe d’interaction entre l’α-chymotrypsine et la proflavine a été réalisé sur base de la structure cristallographique du complexe entre cet inhibiteur et une protéase apparentée à la chymotrypsine, la thrombine. Il ressort de l’analyse du modèle obtenu que la proflavine est profondément enfouie dans le subsite S1 de l’enzyme et présente une très grande complémentarité de surface avec cette poche hydrophobe. Nous avons également pu constater la présence de plusieurs molécules d’eau immobilisées au sein du complexe, et d’une molécule en particulier faisant office de relais de liens-H.

L’étude de l’interaction entre l’α-chymotrypsine et la proflavine par RMN du 1H a été précédée par une étude de l’effet du degré de maturité de l’enzyme sur les interactions liant les différents résidus composant la triade catalytique (Asp102, His57 et Ser195). Lors de l’activation du précurseur inactif de l’enzyme, le chymotrypsinogène, vers la forme mature, l’α-chymotrypsine, il semble en effet que le lien-H entre le NH&949;2 de l’His57 et le Oγ de la Ser195 soit affaibli, contrairement à celui qui relie le NHδ1 de cette même histidine au Oδ1 de l’Asp102. Nous rapportons pour la première fois l’observation de l’influence de la protonation de l’Asp102 sur les déplacements chimiques des protons NHδ1 et NH&949;2 de l’His57. L’étude de l’interaction entre l’α-chymotrypsine et la proflavine par RMN, nous a permis de mettre en évidence l’effet de la complexation du ligand sur l’état d’ionisation des résidus His57 et Asp102 de la triade catalytique, les pKa de ces résidus dans l’enzyme libre valant respectivement 7 et approximativement 4.

Les paramètres thermodynamiques de l’interaction α-chymotrypsine - proflavine et des différents équilibres de protonation/déprotonation qui y sont liés ont été obtenus par spectroscopie d’absorption et ITC. Cette dernière technique constitue un outil précieux pour l’étude d’interactions moléculaires car il s’agit de la seule technique expérimentale permettant la mesure directe de l’enthalpie d’interaction. Lorsque des équilibres de protonation/déprotonation sont thermodynamiquement liés à l’interaction, il s’agit également de la seule technique permettant la quantification de ces effets. En mesurant la constante d’affinité et l’enthalpie d’interaction observées à différents pH et dans différents tampons, nous avons pu, sur base du modèle obtenu par RMN, déterminer les paramètres thermodynamiques intrinsèques des différents équilibres.

La corrélation entre les données thermodynamiques obtenues par ITC et spectroscopie d’absorption et les données structurales obtenues par RMN et sur base de l’analyse du modèle du complexe d’interaction, nous a permis de rationaliser les facteurs à la base de l’interaction préférentielle de l’inhibiteur avec une des formes de l’enzyme. L’interaction entre l’α-chymotrypsine et la proflavine est la plus favorable lorsqu’à la fois l’His57 et l’Asp102 sont déprotonnés. Cette interaction est caractérisée par un terme enthalpique favorable et un terme entropique légèrement défavorable. Ce dernier terme s’expliquerait en partie par l’immobilisation dans le site d’interaction de plusieurs molécules d’eau. L’affinité entre l’α-chymotrypsine et la proflavine diminue lorsque l’His57 se protonne. La répulsion électrostatique entre les charges positives de la proflavine et de l’His57 est vraisemblablement un des facteurs permettant d’expliquer cette diminution de la constante d’affinité. Nous n’avons pu mettre en évidence d’interaction entre ces deux molécules dès lors que l’Asp102 est protonné, malgré que ce résidu soit situé relativement loin de la proflavine dans le complexe. Il s’agit donc d’un effet indirect, probablement relayé par l’His57. Tant que l’Asp102 est déprotonné, sa charge négative compenserait la charge positive de l’His57 et réduirait la répulsion électrostatique avec la proflavine, ce qui n’est plus le cas lorsque l’aspartate se protonne.
Doctorat en sciences appliquées
info:eu-repo/semantics/nonPublished

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Abaei, Tafresh Alireza [Verfasser], Hans [Akademischer Betreuer] Hofsäss, Peter [Akademischer Betreuer] Dechent, Astrid [Akademischer Betreuer] Pundt, Joerg [Akademischer Betreuer] Enderlein, Stephan [Akademischer Betreuer] Waack, and Carsten [Akademischer Betreuer] Damm. "Localized Proton Magnetic Resonance Spectroscopy of Mouse Brain In Vivo at High Magnetic Field Strength / Alireza Abaei Tafresh. Gutachter: Hans Hofsäss ; Peter Dechent ; Astrid Pundt ; Joerg Enderlein ; Stefan Waack ; Carsten Damm. Betreuer: Hans Hofsäss." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/1059004631/34.

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Zalcman, Amy. "The Use of Magnetic Resonance Imaging and Proton Spectroscopy to Identify Critical Tissues in Dogs with Duchenne Muscular Dystrophy for Future Assessment of Therapeutic Intervention| A Pilot Study." Thesis, University of Missouri - Columbia, 2019. http://pqdtopen.proquest.com/#viewpdf?dispub=13850759.

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Duchenne’s Muscular Dystrophy is a debilitating disease that affects skeletal and cardiac muscle of 1 in 5000 male births. In the last thirty years, the gene responsible for the encoding of Dystrophin has been identified, sequenced and the variations of mutations described. There remains a void in the successful treatment of the disease although corticosteroid use has proven useful in delaying progression. Novel therapies are produced in the categories of virus-mediated gene delivery and stem cells, but evaluating their efficacy is hindered by an inability to contemporaneously assess the changes in muscle. The purpose of this pilot study was to characterize the changes in skeletal and cardiac muscle in a clinically advanced population of dogs affected with Duchenne Muscular Dystrophy. Using traditional sequences, delayed gadolinium enhancement, novel sequences and spectroscopy, changes in the investigated muscle were characterized. By establishing the differences between affected and unaffected dogs, the long-term goal of this body of work is to characterize these changes longitudinally and design a non-invasive method for tissue assessment as novel treatments are trialed.

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Hatchondo, Laura. "Spectroscopie par Résonance Magnétique : Étude des variations diurnes des mesures de concentrations de métabolites cérébraux et applications cliniques." Thesis, Poitiers, 2019. http://www.theses.fr/2019POIT1804.

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La SRM du proton (SRM-1H) est une technique d’imagerie métabolique de plus en plus utilisée en routine clinique (tumeurs cérébrales), mais aussi dans les études de neuroimagerie explorant le métabolisme cérébral des pathologies neurologiques ou psychiatriques (notamment les Troubles Obsessionnels Compulsifs TOC). Actuellement, les séquences SRM-1H sont réalisées à un temps donné, sans prise en compte de l’horaire auquel l’examen est réalisé. Or, à ce jour, nous ne pouvons pas affirmer que les concentrations de métabolites cérébraux sont stables sur 24h. Par ailleurs, nous savons que le corps humain est soumis à une rythmicité circadienne entraînant des modifications globales (sécrétions hormonales, température corporelle, tension artérielle, notamment). L’objectif principal de ce travail était d’étudier, sur une population de sujets sains, les variations diurnes des mesures de concentration des métabolites cérébraux (NAA, Cho, Cr et lactates) en SRM-1H, dans plusieurs régions d’intérêts : noyau caudé (NC), putamen, thalamus, cortex cingulaire antérieur (CCA) et postérieur (CCP), cortex insulaire (CI), substance blanche (SB) de la portion antérieure/frontale des radiations du corps calleux et de la portion postérieure/pariétale des radiations du corps calleux, et ce sur 3 périodes « critiques » de la journée au niveau du rythme circadien humain : 7h30, 13h30 et 18h00. Par ailleurs, nous avons comparé les concentrations de métaboliques dans chaque région cérébrale en fonction du sexe des sujets. Nous avons cherché une possible modélisation mathématique de ces variations. Enfin, à la lumière des résultats, nous avons rediscuté notre étude clinique sur les patients TOC sévères. 30 sujets sains sélectionnés en termes d’âge pour former un groupe homogène ont été inclus dans cette étude descriptive, monocentrique, transversale, prospective et comparative. Tous ont bénéficié des 3 examens IRM comprenant la séquence SRM-1H aux heures prédéfinies sur une IRM-3T. Nos résultats ont mis en évidences des variations significatives dans l’ensemble des structures étudiées, principalement entre l’IRM1 (07h30) et l’IRM2 (13h30), et entre l’IRM1 et l’IRM3 (18h00). Les zones présentant les variations les plus significatives (p < 0,01) ont été les noyaux gris centraux, le CCP et le CI. Les métabolites ont tous été concernés par des variations significatives ; dans une moindre mesure pour les lactates confirmant que ce tampon énergétique est relativement stable en conditions physiologiques. L’analyse comparative selon le sexe des sujets a retrouvé des différences significatives dans plusieurs régions corticales et au niveau de la SB postérieure/pariétale du corps calleux. Par ailleurs, la modélisation mathématique « sinusoïdale » est apparue comme la plus convaincante en rendant compte, via les simulations numériques, des variations de concentrations métaboliques compatibles avec la viabilité biologique connue. Elle a confirmé que les lactates ne fluctuent pas dans la journée, mais présentent des variations différentes suivant certaines régions. Enfin, ces résultats remettent en perspective notre travail clinique sur les TOC en apportant des critiques sur les horaires choisis pour les IRM, et en suggérant la place des lactates dans le circuit neurologique pathophysiologique connu de cette pathologie. Ce travail a donc mis en évidence une variabilité globale du métabolisme cérébral au cours de la journée. Il remet en question les résultats des études précédentes qui auraient utilisé des horaires différents dans et entre les groupes de sujets étudiés. Pour l’avenir, la mise en place d’un protocole horaire plus rigoureux sera indispensable dans le cadre des études en SRM-1H. Enfin, l’on peut supposer que le métabolisme cérébral pourrait suivre une variabilité circadienne modélisable grâce aux outils mathématiques, ouvrant un champ de perspectives passionnant pour de futures études plus poussées
Magnetic Resonance Spectroscopy (MRS) is a Magnetic Resonance Imaging (MRI) technique allowing a non-invasive and non-radiative study of the neurophysiology and neurobiochemistry of human body tissues. Nowadays, proton MRS (1H-MRS) is used routinely, particularly in brain tumor imaging tests, but also in neuroimaging studies exploring the cerebral metabolism of neurological or psychiatric conditions. Currently, 1H-MRS is scheduled without taking into account the time at which the examination is performed. But to date, we cannot assert if the concentrations of brain metabolites are stable over 24 hours. We know that the human body is subject to circadian rhythmicity leading to global changes including, among others, hormonal secretions (TSH, cortisol, melatonin, carbohydrate metabolism), body temperature, blood pressure.The main objective was to study, in a population of healthy subjects, diurnal variations in the concentration of brain metabolites (NAA, Cho, Cr and lactates) in 1H-MRS, in several regions of interest : caudate nucleus (CN), putamen, thalamus, anterior cingulate cortex (ACC) and posterior (PCC), insular cortex (IC), white matter (WM) of the anterior / frontal portion of the corpus callosum radiation and posterior / parietal portion of the corpus callosum radiation, at 3 "critical" times of the day : 7:30 a.m., 1:30 p.m. and 6:00 p.m. In addition, we compared the metabolic concentrations in each cerebral region according to the sex of the subjects. We looked for a modeling of these variations using the mathematical tools. Finally, we discussed the results of our clinical study on patients with severe Obsessive-Compulsive Disorder (OCD).30 healthy subjects selected in terms of age to be homogeneous were included in this descriptive, monocentric, transverse, prospective and comparative study. All of them benefited from three MRI examinations including the 1H-MRS sequence at the defined hours on an 3T MRI.Our results revealed significant variations in all the structures studied, mainly between MRI1 (7:30 a.m.) and MRI2 (1:30 p.m.), and between MRI1 and MRI3 (6:00 p.m.). Areas with the most significant changes (p <0.01) were basal ganglia, CCP and CI. Metabolites have all shown significant variations; to a lesser extent for lactates confirming that this energy buffer is stable under physiological conditions. The comparative analysis by sex of the subjects found significant differences in the CCA, CCP, NC, putamen and posterior / parietal SB of the corpus callosum. In addition, "sinusoidal" mathematical modeling appeared to be the most confident as numerical simulations, remained consistent with biological viability. It confirmed that lactates do not fluctuate during the day, but vary from one region to another suggesting functional pathway involvement and potential usefulness for clinical monitoring. Finally, we discussed again our clinical study on OCD considering the schedules chosen for MRI examinations and the potential role of lactates in the neuropathophysiological network of OCD.This work has shown that cerebral metabolism has significant variations during the day. The results of previous studies must be reconsidered if they used different schedules in and/or between the groups of subjects studied. In the future, the 1H-MRS studies will need a more rigorous protocol on the time of MRI examinations. Finally, these results suggest that cerebral metabolism may follow a circadian variability that can be modeled using mathematical tools. This opens a field of exciting opportunities for extensive investigations, with more measurement points on 24 hours and biological or even genetic correlations
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Mirbahai, Ladan. "Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/619/.

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Early detection of biomarkers of tumour treatment response improves clinical management, in vivo. Magnetic resonance spectroscopy (MRS) has demonstrated potential for identifying early biomarkers of effective treatment. However, more detailed in vitro studies are required to improve our understanding and facilitate its use. The aim of this study is to determine ¹H high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) biomarkers of cytostasis and cell death in a rat glioma BT4C cell line. Cytostasis and cell death were induced in BT4C cells using cisplatin and substrate free medium, respectively. Cell viability was examined by various techniques. The lipid and metabolite alterations in whole cells were investigated by ¹H HR-MAS NMR. Significant alterations in lipids and metabolites were detected in response to cytostasis or necrosis. NMR lipid accumulation was associated with an increase in cytoplasmic lipid droplets seen prior to morphological and molecular markers of cell death. Significant differences were detected in individual choline containing metabolites (CCMs), emphasising the importance of identifying CCMs separately. Alterations were also detected in lactate, alanine, glycine, glutamate, and succinate levels, suggesting changes in the energy metabolism pathways which may provide novel biomarkers in vivo. ¹H HR-MAS NMR reveals alterations in lipids and metabolites during cytostasis and cell death which may provide early markers of treatment efficacy.
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Münch, Frédéric [Verfasser]. "Metabolic profiling in experimental autoimmune myocarditis (EAM) in a rodent model using ex-vivo proton magic angle spinning magnetic resonance spectroscopy (1H-MAS-MRS) to detect myocardial injury / Frédéric Münch." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1140486829/34.

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Koch, Katharina [Verfasser], Jaroslaw [Gutachter] Maciaczyk, and Dieter [Gutachter] Willbold. "Analysis of metabolic reprogramming during the enrichment of glioblastoma stem-like cells in glioblastoma via high resolution proton nuclear magnetic resonance (HR 1H-NMR) spectroscopy / Katharina Koch ; Gutachter: Jaroslaw Maciaczyk, Dieter Willbold." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2020. http://d-nb.info/1223705242/34.

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Nemeth, Angéline. "Développement et validation de stratégies de quantification lipidique par imagerie et spectroscopie proton à 3T : Application à l’étude de la surnutrition." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI089/document.

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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
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Mantovani, Cristina de Faria. "Análise metabolômica (1H RMN) do líquido sinovial de equinos hígidos e acometidos por osteocondrite dissecante." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/10/10137/tde-10042014-144355/.

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A osteocondrite dissecante (OCD) é uma das principais doenças que afetam os equinos jovens e uma das condições incluídas nas Doenças Ortopédicas do Desenvolvimento. Por se tratar de importante afecção articular, a OCD pode ser responsabilizada por perdas econômicas substanciais em decorrência da diminuição do desempenho atlético e reprodutivo dos animais acometidos. Sua etiologia é considerada multifatorial sendo associada a fatores nutricionais, endócrinos, genéticos e biomecânicos. A análise dos biomarcadores do líquido sinovial fornece dados fundamentais acerca das alterações representativas de inflamação e danos à cartilagem articular, por isso o monitoramento do ambiente articular caracteriza-se como uma importante ferramenta para o diagnóstico e acompanhamento da progressão da doença. A análise metabolômica por Ressonância Magnética Nuclear de prótons de hidrogênio (1H RMN) é um método de avaliação holístico, simultâneo e em tempo real, dos metabólitos de pequenas moléculas presente no líquido sinovial, capaz de fornecer dados a respeito da progressão da doença, da resposta a tratamentos e de determinar biomarcadores. No presente estudo objetivou-se estabelecer o perfil metabólico global do líquido sinovial de equinos acometidos por OCD, estudar a aplicabilidade da 1H RMN no diagnóstico da OCD e avaliar a possibilidade de distinção entre os líquidos sinoviais de articulações com OCD sintomática e assintomática. A determinação do perfil metabólico do líquido sinovial de equinos hígidos e acometidos por OCD assintomática e sintomática resultou em 32 metabólitos comuns às três condições articulares. Além destes, 2 compostos foram identificados somente nas articulações doentes, sendo eles o propilenoglicol e o composto aromático, porém, não foi possível diferenciar as articulações com OCD assintomática das articulações sintomáticas, pois ambos os grupos apresentavam metabólitos semelhantes e com intensidades similares.. Na comparação entre a intensidade dos espectros, observaram-se aumentos dos metabólitos glicose, glutamina, etanol, leucina, isoleucina, dimetilsulfona, creatina, creatinina, Nacetilglucosamina e N-acetilglutamina e -metil histidina e dos compostos propilenoglicol e composto aromático nas articulações com OCD com relação às hígidas. Dos metabólitos que apresentaram redução na intensidade dos espectros das articulações doentes têm-se o 3- hidroxibutirato e o acetato. Outros metabólitos demonstraram a mesma intensidade de sinal para os três tipos de articulação, sendo eles: piruvato, citrato, metionina, histidina, tirosina, valina, lactato, alanina, glicina, glicerol e fenilalanina. A análise estatística por PCA foi capaz de realizar o agrupamento dos espectros e atribuir a importância do composto aromático na diferenciação entre os animais hígidos e doentes. A análise metabolômica por 1H NMR mostrou-se técnica com alta reprodutibilidade entre as amostras e sensibilidade de detecção dos componentes do líquido sinovial, revelando claras diferenças entre os perfis bioquímicos de articulações hígidas e acometidas por OCD, indicativo das alterações metabólicas que ocorrem com a progressão desta doença, relacionadas principalmente com o processo de degradação cartilagínea. Este estudo salienta o potencial da análise metabolômica em fornecer uma nova perspectiva dos processos bioquímicos envolvidos na progressão da OCD.
Osteochondritis dissecans (OCD) is one of the most common diseases affecting young horses and one of the conditions classified as Developmental Orthopedic Diseases. As an important joint disorder, OCD is held responsible for substantial economic losses in consequence of the decrease in athletic and reproductive performance in affected horses. The condition presents a multifactorial ethiology, related to nutritional, endocrine, genetic and biomechanical factors, although its pathogeny is well established, associated with a disturbance of the process of endochondral ossification. Synovial fluid biomarkers analysis provide data regarding changes representative of inflammation and articular cartilage damage, which is why monitoring the joint cavity is an important tool for diagnosis and assessing disease progression. Proton Nuclear Magnetic Resonance spectroscopy is a holistic, simultaneous and real time approach, of the metabolites present in the synovial fluid, offering the potential to provide data regarding disease progression, response to treatment and to determine disease biomarkers. The aim of the present study was to establish the global metabolic profiling of normal and osteochondritic synovial fluid, to evaluate the applicability of the 1H RMN in the diagnosis of OCD, and to asses possible distinctions between symptomatic and asymptomatic horses. The metabolic profile determination resulted in 32 common metabolites to the three joint conditions. Moreover, 2 compounds were identified exclusively in the diseased joints, namely propylene glycol and aromatic compound, but we were unable to discern between asymptomatic and symptomatic individuals for both groups presented similarities in metabolites as well as their concentrations. When comparing spectral intensities, we observed marked increases in the metabolites glucose, glutamine, ethanol, leucine, isoleucine, dimethyl sulphone, creatine, creatinine, N-acetylglucosamine, N-acetylglutamine and -methyhistidine, besides the compounds propylene glycol and aromatic compound, in the affected joints compared to the healthy ones. Decrease in spectral intensities were related to the metabolites 3-hydroxybutirate and acetate in affected joints. Other metabolites showed no difference in intensities in all joint conditions, those being pyruvato, citrate, methionine, histidine, tyrosine, valine, lactate, alanine, glycine, glycerol and phenylalanine. PCA based statistical analysis was able to group spectra and to ascribe the importance of the aromatic compound in differentiating healthy from diseased joints. 1H RMN spectroscopy showed high reproductability between samples and sensitive in detecting synovial fluid compounds, unveiling clear diferences between the biochemical profiles of healthy and OCD affected joints, thus indicating metabolic alterations occuring with disease progression, related mainly with the cartilage degradation process. This study projects the potential of metabolomics analysis in providing a new perspective of the biochemical processes involved in OCD progression.
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41

Ouldamer, Lobna. "Evaluation de la spectroscopie par résonance magnétique du tissu adipeux mammaire comme marqueur non invasif de la part nutritionnelle du cancer du sein." Thesis, Tours, 2016. http://www.theses.fr/2016TOUR3304.

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La composition en acides gras du tissu adipeux mammaire est reconnue comme marqueur qualitatif de la consommation lipidique antérieure mais aussi de la part nutritionnelle du risque / pronostic du cancer du sein. Ceci ouvre la perspective d’individualiser dans la population générale, un groupe de personnes à risque, susceptibles de bénéficier d’une intervention nutritionnelle ciblée. L’approche du dépistage d’une population à risque par l’utilisation de la composition du tissu adipeux comme biomarqueur se heurte i) à l’aspect invasif que représente le prélèvement d’un fragment de tissu adipeux mammaire, et ii) à la lourdeur contraignante du conditionnement et de l’analyse systématique des acides gras du tissu adipeux. Les méthodes analytiques actuellement disponibles sont incompatibles avec la perspective d’un dépistage de masse. Cependant, les descriptions récentes de l’utilisation de la spectroscopie par résonance magnétique (SRM) pour décrire la composition lipidique des triglycérides du tissu adipeux permettent d’envisager de l’utiliser dans cet objectif. Ce travail de thèse présente: 1) l’évaluation de la SRM pour caractériser la composition en acides gras du tissu adipeux chez l’animal (le rat) suite à une intervention nutritionnelle, 2) l’évaluation du profil lipidique du tissu adipeux par SRM chez la femme sur une plateforme clinique 3T, 3) l’étude des liens entre la composition en acides gras du tissu adipeux et la présentation du cancer du sein, et 4) la comparaison des données de la SRM in vitro (11.7T) et in vivo (3T) du tissu adipeux chez des patientes prises en charge pour un cancer du sein avec les données de la chromatographie gazeuse
Fatty acid composition of the white adipose tissue remains the most reliable qualitative biomarker of previous dietary intake of fatty acids and may provide information on the nutritional part of the risk or evolution of breast cancer. This opens the prospect of individualization of women at high nutritional risk of breast cancer that may benefit from a targeted nutritional intervention but 1) the need for biopsy and 2) subsequent time-consuming biochemical analyses hamper any application of this approach. Proton magnetic resonance spectroscopy (1H-MRS) of adipose tissue lipids represents an appealing, non-invasive approach, which could circumvent these limitations. This manuscript reports: 1) an assessment of feasibility of (1H-MRS) to evaluate the consequences of a nutritional intervention in a rat mammary tumor model on the adipose tissue fatty acid composition, 2) an assessment of the feasibility of in vivo measurement of the fatty acid composition of breast adipose tissue by (1H-MRS) on a clinical platform, 3) an assessment of the relation of specific patterns of composition of adipose tissue fatty acids with the presentation of breast cancer, and 4) a comparison with gas chromatography of (1H-MRS) data acquired on breast adipose tissue in vitro (11.7T) and in vivo (3T) on patients managed for breast cancer
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42

Ruschke, Stefan Albert [Verfasser], Dimitrios [Akademischer Betreuer] Karampinos, Dimitrios [Gutachter] Karampinos, Axel [Gutachter] Haase, and Marion I. [Gutachter] Menzel. "Quantification of Proton Density Fat Fraction and Fatty Acid Composition of Triglycerides in Musculoskeletal Tissues using Magnetic Resonance Imaging and Spectroscopy / Stefan Albert Ruschke ; Gutachter: Dimitrios Karampinos, Axel Haase, Marion I. Menzel ; Betreuer: Dimitrios Karampinos." München : Universitätsbibliothek der TU München, 2018. http://d-nb.info/116879854X/34.

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43

Zang, Tuo. "Quantitative characterization of paediatric burn blister fluid." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/122968/1/Tuo_Zang_Thesis.pdf.

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Burn injury is a highly traumatic event for any infant or child. The degree of burn severity often determine the treatment operations and the extent of later scar formation, which may require long-term surgical remediation or skin grafting. This investigation quantitatively characterises the biochemical composition of burn blister fluid from paediatric patients using advanced analytical techniques. The correlation of the abundance of proteins and metabolic molecules were explored by statistical and bioinformatics methods. Thus, this study is able to provide a timely and objective measurement that may reflect the burn wound microenvironment and assist clinical diagnosis.
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44

Lundberg, Staffan. "Rolandic Epilepsy : A Neuroradiological, Neuropsychological and Oromotor Study." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4133.

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45

Raffin, Luciana Sanchez. "Avaliação das lesões císticas da neurocisticercose na difusão e espectroscopia de prótons pela ressonância magnética." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-13102014-110344/.

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OBJETIVO: O objetivo deste estudo é descrever as características do sinal nas lesões císticas da neurocisticercose nas imagens ponderadas em difusão e os metabólitos encontrados na espectroscopia de prótons. MATERIAL E MÉTODOS: Estudaram-se 38 pacientes (39 lesões) com neurocisticercose, usando-se difusão e espectroscopia de prótons. Os exames foram realizados em um magneto de 1,5 T (Signa Horizon LX: GE Medical Systems). A difusão foi realizada no plano axial, com múltiplos cortes com seqüência eco planar. A espectroscopia de prótons utilizou a seqüência PRESS (point-resolved spectroscopy) com TR of 1500 ms e TE de 30/135 ms. RESULTADOS: Os cistos apresentaram intensidade de sinal similar a do líquido cefalorraqueano (LCR) na difusão e valores de CDA sobreponíveis, variando de 1,36 a 3,18 x 10-3 mm2/s. Os picos detectáveis na espectroscopia foram lactato (96,3%), succinato (48%), alanina (40%), lipídeos (15%), aminoácidos citosólicos (7,5%) e acetato (3,7%). CONCLUSÃO: As lesões císticas da neurocisticercose apresentaram hipossinal na difusão e os picos encontrados na espectroscopia de prótons, em ordem decrescente de freqüência, foram lactato, succinato, alanina, lipídeos, aminoácidos citosólicos e acetato
PURPOSE: The objective of this study is to describe the signal behavior of cystic neurocysticercotic lesions on diffusion-weighted imaging (DWI) and single voxel proton spectroscopy findings. MATERIALS AND METHODS: We studied 38 patients (39 lesions) with neurocysticercosis, using diffusion-weighted images and proton MR spectroscopy. The examinations were performed on a 1.5 T scanner (Signa Horizon LX: GE Medical Systems). DWI was performed in the axial plane, using a multisection single shot echo planar pulse sequence. The single voxel proton spectroscopy technique used was the point-resolved spectroscopy (PRESS) sequence with a TR of 1500 ms, short and long TE of 30/135 ms. RESULTS: The cysts presented similar signal intensity to the CSF on DWI, with comparable ADC values, ranging from 1.36 to 3.18 x 10-3 mm2/s. The detectable peaks were lactate (96.3%), succinate (48%), alanine (40%), lipids (15%), cytosolic amino acids (7.5%) and acetate (3.7%). CONCLUSION: The cysts of neurocysticercosis presented hyposignal on DWI and peaks of lactate, succinate, alanine, lipids, cytosolic amino acids and acetate in proton spectroscopy, in decreasing order of frequency
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46

Yee, Sidney. "Solution-State Proton Nuclear Magnetic Resonance (NMR) Spectroscopic Studies of the Active Site of Myoglobins in Various Ligated States: Models for Macromolecule-Substrate Binding and Advancement of Paramagnetic NMR Techniques." PDXScholar, 1993. https://pdxscholar.library.pdx.edu/open_access_etds/1253.

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This work focuses on pigmy sperm whale and horse myoglobins (Mbs), which are distinguished by a single heme pocket residue variant in the CD3 position, when the heme iron is in the +3 oxidation state (i.e. the met form). The strategy employed is as follows: (i) assign heme peripheral protons; (ii) assign the amino acid residues from the heme cavity; (iii) assess the dynamics of ligand binding in the active site by means of hydrogen Iability, solvent isotope effects, and heme-insertion isomer trapping, all by NMR methods. The results of these studies portray dynamic solution structure of the Mb ligand binding site, and provide a set of standard parameters for the studies of larger hemoproteins. The findings are also important for understanding protein-ligand interactions in general. My research investigates the mixed spin metazido and metimidazole complexes of Mbs for the following reasons. First, the allosteric properties of hemoglobin arise mainly from the transition between its two possible quaternary structures. This can be studied by paramagnetic NMR because it is one of the most sensitive tools in terms of changes in the molecular and/or electronic structure of the heme. Second, both the N₃- and imidazole (lm-) complexes are good compromises, in terms of sizes, between the small diatomic oxygen or CN⁻ molecules and the bulky phenyl group. Thus, we can determine the influence of ligand size on structural perturbation of the Heme crevice by comparison among the different size groups. Third, the saturation-transfer phenomenon between metMbIm and metMbH₂0 provides a route to assignments in metMbH₂0 by using assignments of metMbIm. This is crucial because metMbH₂0 is the basis of theoretical calculations of the isotropic shift due to axial ligand field in pure high-spin hemoproteins. Finally, the importance of the metMbIm is underscored by the fact that it is a bis-imidazolium complex, which can then serve as a model other bis-histidyl proteins. Most of the heme peripheral resonances of metEqMbIm and metEqMbN₃ were identified by means of two-dimensional NOESY,COSY, and EXSY spectroscopy. The strongly relaxed upfield protons in metMbIm were assigned based on steady-state 1D NOE and T₁ experiments. Based on the results from metMblm in which saturation transfer of one upfield resonance led to two different free ligand peaks, bound Im equilibration was envisioned and proven by the divergence of broad downfield heme methyl peaks into two peaks each, showing distinctive population preference of each isomer. Dicyanoheme probe, as well as hydrogen Iability comparison studies between pigmy sperm whale Mb and horse Mb in the azido and imidazole states, asserts that single variant pocket residue CD3 is crucial in gating the ligand mobility into and out of the active site. The assignments of heme peripheral and upfield resonances enabled the subsequent assignments of some heme pocket amino acid residues. The facile exchange of bound Im with solvent H₂0 lays the ground work for identification of heme pocket residues in metMbH₂0. Furthermore, while deuterated heme previously allowed only assignment of the non-diastereomeric specific heme 2-vinyl β proton, saturation-transfer from horse imidazole Mb affords the specific identification of 2Hᵦt.
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47

Gudlowski, Yehonala. "Neurophysiologische Substrate von Störungen des Belohnungssystems und kognitiver Funktionen bei unmedizierten Schizophreniepatienten untersucht mittels funktioneller Magnetresonanztomographie und 1 H-Magnetresonanzspektroskopie." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät II, 2010. http://dx.doi.org/10.18452/16047.

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Bildgebende Studien haben gezeigt, dass bei schizophrenen Patienten Positivsymptome mit Veränderungen mesolimbischer Aktivierungsmuster unter Einbeziehung des Nucleus accumbens in Zusammenhang stehen. Hierbei ist von besonderem Interesse, dass der Nucleus accumbens Teil des Belohnungssystems ist, wobei die integrale „Bewertung“ belohnungsanzeigender Reize präfrontalen kortikalen Strukturen, insbesondere dem anterioren Zingulum, zuzurechnen ist. Bereits in der Antizipationsphase potentiell belohnender Reize, werden vermutlich zur Berechnung von Prädiktionsabweichungen dopaminerge Signale in der VTA generiert und modulieren den Nucleus accumbens. Es gibt zahlreiche Hinweise, dass glutamaterge Neurone des anterioren Zingulums die Dopaminausschüttung im Nucleus accumbens beeinflussen, und dass diese Modulation bei Erkrankungen wie der Schizophrenie beeinträchtigt ist. Ziel der vorliegenden Arbeit war es, mittels funktioneller Magnetresonanztomographie und Protonen Magnetresonanzspektroskopie, Hinweise über den Zusammenhang zwischen der glutamatergen Neurotransmission des ACC und belohnungsassoziierter Dopaminausschüttung im Nucleus accumbens bei 23 gesunden Probanden und bei 23 unmedizierten schizophrenen Patienten zu erlangen. Die Ergebnisse weisen darauf hin, dass die gegenseitige Modulation von anteriorem Zingulum und Nucleus accumbens bei schizophrenen Patienten gestört ist. Dieses und weitere Ergebnisse wurden im theoretischen Rahmen der NMDA-Rezeptor-Hypoaktivität und einer gestörten Balance zwischen Dopamin-D1- und Dopamin-D2-Rezeptor-Aktivität als pathophysiologische Korrelate schizophrener Erkrankungen diskutiert.
Imaging studies have demonstrated that for schizophrenic patients a correlation exists between positive symptoms and changes in the patterns of mesolimbic activity. Especially the changes in the ncl. accumbens (Nac) were interpreted in connection with the reward system. The signals indicating reward are thought to be processed by the anterior cingulum (ACC). These structures attribute meaning to the reward signals. In the anticipation phase of a potentially rewarding stimulus, dopaminergic signals from the VTA are generated in prediction of expected or aberrant outcome, thus modulating the Nac. Data indicate a direct modulation of the Nac. by glutamatergic neurons of the anterior cingulum. A major aim of this thesis is to establish a connection between the reward associated dopaminergic signals of the ncl. accumbens and the glutamatergic projections of the acc in unmedicated schizophrenic patients and healthy controls. The methods included measurements of proton magnetic resonance spectroscopy (1H-MRS) and functional MRI-scans done at a 3-Tesla tomograph. The paradigm applied was a modified version of the monetary incentive delay paradigm (Knutson et al. 2000). In healthy volunteers we found a significant negative correlation between the glutamate concentration in the ACC and the BOLD-contrast in the Nac (reward versus neutral), in contrast to the findings in schizophrenic patients. A significant higher BOLD-contrast was seen in the anticipation phase in healthy controls. The results were incorporated in a model of NMDA-R-Hypoaktivity. In addition to discussing the functional aspects for the structures involved the model was further expanded to include the hypothesis of a disturbed balance between dopamine-D1- and -D2-receptor activity and a dysfunctional hippocampal gating-process. The so constructed model suggests a profound striato-thalamo-cortical filter disturbance as the basis of the observed aberrations in the reward processing in schizophrenic disorders.
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48

Chatel, Benjamin. "Fonction et métabolisme énergétique musculaires dans un modèle de souris drépanocytaires et identification des mécanismes responsables des échanges des protons entre le muscle et le sang." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0174.

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La drépanocytose est la maladie génétique la plus répandue au monde. Elle est caractérisée par la synthèse d’une hémoglobine anormale S (HbS) et associée à une altération des processus de distribution d’oxygène. Bien que ces anomalies puissent impacter le muscle strié squelettique, ce tissu n’a que très rarement été étudié. L’objectif de ce travail de thèse était de décrire les réponses fonctionnelles et énergétiques du muscle à l’exercice aigu, à l’ischémie – reperfusion et à l’entraînement en endurance dans un modèle de souris drépanocytaires, et d’identifier les mécanismes responsables des échanges de protons entre le muscle et le sang.Des souris drépanocytaires sédentaires et entraînées ont été soumises à des protocoles standardisés de repos – stimulation – récupération et repos – ischémie – reperfusion pendant lesquels la force et le métabolisme énergétique (par spectroscopie de résonance magnétique du phosphore 31) étaient mesurés. Des souris hétérozygotes pour le transporteur de monocarboxylate 1 (MCT1) ont également été soumises au protocole de stimulation. Des analyses in vitro du métabolisme énergétique et des mécanismes de régulation du pH ont également été réalisées.Ce travail a permis de démontrer que les réponses fonctionnelles et énergétiques à l’exercice musculaire et l’ischémie - reperfusion étaient affectées par la présence d’HbS et que l’entraînement en endurance permettait d’améliorer une partie de ces anomalies. Nous avons également observé que MCT1 était responsable de l’entrée des protons dans la cellule au repos, mais peu actif pendant l’exercice
Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is characterized by the synthesis of an abnormal hemoglobin S (HbS) and associated with impairments in oxygen delivery processes. If these abnormalities could impact skeletal muscle, this tissue has been rarely investigated. The aim of this thesis was to investigate muscular function and energetics in response to acute exercise, ischemia – reperfusion and endurance training in a mouse model of SCD, as well as identify the mechanisms involved in proton exchanges between muscle and blood.Sedentary and trained SCD mice were submitted to protocols of rest – stimulation – recovery and rest – ischemia – reperfusion during which muscular force and energetics (by magnetic resonance spectroscopy of phosphorus 31) were measured. Monocarboxylate transporter 1 (MCT1) haploinsufficient mice were also submitted to the stimulation protocol. Several muscles were sampled and permitted to analyze in vitro enzyme activities, content of proteins involved in pH regulation and some markers of oxidative stress.This thesis demonstrated that muscular function and energetics were impaired in SCD mice in response to both exercise and ischemia – reperfusion and that endurance training could alleviate some of these abnormalities, particularly acting on oxidative processes. We have also observed that MCT1 is involved in proton uptake by myocytes at rest, but its action is less important during exercise
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49

Estilaei, Mohammadreza. "Proton magnetic resonance of lung." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0029/NQ27138.pdf.

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50

Borges, Ana Karina Nascimento. "Estudo do metabolismo lipídico através da espectroscopia de prótons por ressonância magnética em seres humanos obesos pré e pós-gastroplastia correlacionando com dados antropométricos, exames laboratoriais e biópsia hepática." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5151/tde-22082008-153128/.

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A influência da obesidade sobre o fígado e a função hepática é tema ainda pouco estudado e discutido, principalmente no Brasil. O crescente aumento da população obesa de maneira global alerta sobre esse grave problema, que hoje em dia, se torna de saúde pública. Amplia-se, cada vez mais, o número de pessoas e a faixa etária atingida. A doença hepática não alcoólica é uma condição clínico-patológica comum caracterizada por depósitos de lipídios em hepatócitos no parênquima hepático. Um espectro de danos ocorrem no parênquima, desde uma simples esteatose macrogoticular podendo evoluir para esteato-hepatite, fibrose e até cirrose. Os casos de esteatose hepática não alcoólica (EHNA) que progridem para cirrose tem sido reconhecidos como a maior causa de morbidade e mortalidade com potencial para progredir para falência hepática. Apesar de haver um aumento na prevalência da doença hepática não alcoólica, os critérios para seu diagnóstico continuam pobremente definidos. A utilização da espectroscopia de prótons na ressonância magnética auxilia na quantificação do conteúdo lipídico hepático e na musculatura da perna (tibial anterior e sóleo), embora venha sendo utilizada apenas em pesquisas. Tivemos como objetivos o estudo do metabolismo lipídico de humanos xii obesos por espectroscopia por ressonância magnética, correlacionando com dados laboratoriais e de biópsias hepáticas. Neste estudo observacional transversal e prospectivo realizado em obesos, que foram submetidos a cirurgia redutora gástrica pela técnica de Capella no Hospital Prof. Edmundo Vasconcelos em São Paulo, foram incluídos 27 pacientes analisados no pré e pós-operatório para descrição dos dados. Foi constatada uma razão masculino/feminino geral de 8 :19 e a faixa etária entre 24 e 55 anos. Os índices de massa corpórea (IMC) eram sempre superiores a 40 Kg/m² para inclusão cirúrgica. Os pacientes obesos que no pré-operatório apresentavam esteatose hepática observada na ressonância magnética e esteatose e/ou esteato-hepatite na biópsia hepática evoluíram com melhora ou resolução no pós-operatório. Em conclusão, em pacientes obesos o grau de esteatose hepática pode ser analisado qualitativa e quantitativamente através da ressonância magnética com espectroscopia assim como, o controle pós tratamento cirúrgico evitando-se a utilização de métodos invasivos, entre eles a biópsia hepática.
The obesity influence on the liver and the hepatic function are themes that are not so discussed or studied, especially in Brazil. The world-wide increasing number of obese people calls the attention to this serious problem, that nowadays, became a public health problem. The number of people and the age of the people who suffer from it is increasing each day more. The non-alcoholic hepatic disease is a common pathological clinic condition caractherized by lipid deposits in hemocytes in the hepatic parenchyma. There are some injuries in the parenchyma, since a single steatosy macrogoticular to a steatohepatitis, a fibrosis and even a cirrhosis (Sass et al., 2005). The non-alcoholic steatosy hepatic (NASH) cases which lead to a cirrhosis have been known as the main causes of death with possibilities to evolute to a hepatic fail. Besides there is an increasing in the non-alcoholic hepatic disease, the means for its diagnosis still remain poorly defined. The protons spectroscopy use, in the magnetic resonance, helps on the lipidic hepatic contents numbers, although it has been used only for researches. We had as a goal the lipid metabolism study of obese human beings, related to the laboratorials data and the hepatic biopsy. On this study, where we observed obese people that were submitted to a gastric reducing surgery by the Capella techinic in the hospital Prof. Edmundo Vasconcelos in São Paulo, were included 27 pacients analyzed on the before and after operation for the datas description. It was noted a male/female general reason 9: 18 and the ages between 24 and 55 years old. The body mass indexes (IMC) were always over 40 Kg/m² to be included in a surgery. The obese patients who presented steatosy hepatic before operatory observed on the magnetic resonance and steatosy and/or steatohepatitis during the hepatic biosy went better on the pos-operatory. Finally, in obese patients the xiv steatosy hepatic degree can be analysed on its qualitativy and quantitativy through the magnetic resonance with spectroscopy, and so the cirurgical pos- treatment control, avoiding the use of invasive methods, among them the hepatic biopsy.
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