The aim is to develop NMR spectroscopy of animal models, in vivo, using 13C, 31P and 1H to follow metabolites, to monitor pH and the energy state, so as to prepare future clinical applications to humans. The core project plans to install and NMR spectrometer with a 20 cm diameter bore capable of measuring animals as large as cats. The magnetic field of 1.89T allows obersvation of 13C NMR at 20 MHz, 31P at 32 MHz and 1H at 80 MHz. By the use of surface coils and a focussed magnetic field it will be possible to obtain signals from localized regions as small as 1.5 cm diameter. We will install proton decoupling for 13C observe and will minimize the heating effects so as not to be harmful. Various instrumental improvements will be attempted so as to obtain well resolved NMR spectra, capable of following metabolic flows in real time. The specific projects include studies of brain, liver and tumors in living animals. The brain studies will determine normal glucose pathways to amino acids and other products by 13C NMR generally starting from 13C labeled glucose. It is expected that we should be able to detect glutamate, glutamine, Gamma-amino butyric acid, aspartate and lactate and in some cases to determine biosynthetic pathways and compartmentation. The effects upon these pathways of hypoxia, restraints and seizures will be measured in order to improve and extend our biochemical understanding of these states. The liver studies will follow the gluconeogenic pathway, following fluxes and hormonal effects. In the tumor studies attempts will be made with 31P and 13C NMR to determine the hypoxic fraction of tumors, in vivo, and to monitor its response to different radiation treatments in order to increase their effectiveness. In these studies we shall be preparing for related investigations of disease states in humans.
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