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Title: Multidimensional in vivo NMR
Author: Welch, John
ISNI:       0000 0001 3565 5929
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2001
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A proton nuclear magnetic resonance spectrum of the brain in vivo contains peaks from every proton-containing molecule in the brain. Sensitivity limitations mean that only those molecules present at concentrations of at least a few millimolar are detectable in a reasonable period of time; this still leaves many important molecules such as amino acids and other small metabolites. Most of their resonance frequencies fall in the region between 1.0 and 4.5 p.p.m. A typical linewidth in vivo is about 0.05 p.p.m., so the number of distinct peaks observable is restricted. The use of two-dimensional NMR techniques such as COSY can spread peaks out into a second dimension enabling otherwise overlapping peaks to be resolved. This thesis describes the development, testing and application of two such 2D NMR pulse sequences, dubbed ISIS-COSY and ISIS-JRES. They are based on an existing magnetisation localisation sequence and excite detected magnetisation in a manner analogous to the high-resolution sequences COSY and 2D J-resolved spectroscopy. A method for quantifying the metabolites visible in an ISIS-COSY spectrum from their cross-peak intensities is described, and results presented from both control rat brains and those of animals treated with vigabatrin, an inhibitor of GABA-transaminase that has the effect of increasing brain γ-amino butyric acid (GABA) levels. Further applications mentioned are in the study of neutrophil-infiltrated rat brain and adaptation of the ISIS-COSY technique for human use.
Supervisor: Blamire, Andrew ; Dixon, Ruth Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: NMR Spectroscopy ; Nuclear Magnetic Resonance ; In Vivo ; brain ; Vigabatrin