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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:393788 |
| Date | January 2001 |
| Creators | Welch, John |
| Contributors | Blamire, Andrew : Dixon, Ruth |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:876ed795-9e23-4d53-a407-0a29f7c9ea21 |
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