This project will use newly developed chemically specific, non-invasive magnetic resonance spectroscopic methods to study cerebral metabolism in humans. 1H methods will be used to study the rate of decline of brain phenylalanine in young adult phenylketonurics who go on a low-phenylalanine diet after having chosen previously not to follow such a diet, and to search for evidence of lipid degradation in patients with stroke and dementia. Combined 1H and 13C methods will be used to monitor rates of entry of 13C and eventual steady state 13C fractional enrichment in amino acid and elevated lactate pools when 13C-labeled glucose is given intravenously. The range of variation of amino acid labeling and optimum 1-13C-glucose infusion schedules will be determined in normal subjects of varying age and weight during quiet wakefulness, and then during sensory stimulation and in patients with dementia and complex partial epilepsy. Cerebral lactate elevated by stroke will be studied to evaluate it steady state 13C fractional enrichment as a measure of an ischemic penumbra. The results are expected to provide new information about normal cerebral metabolism and about how the pathophysiological processes at work in dementia, stroke, and epilepsy affect the rate of glucose entry into the brain, the metabolic activity of elevated lactate pools, and rates of amino acid turnover.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027883-02
Application #
3414308
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Zhong, J; Petroff, O A; Pleban, L A et al. (1997) Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks. Magn Reson Med 37:1-6
Zhong, J; Petroff, O A; Prichard, J W et al. (1995) Barbiturate-reversible reduction of water diffusion coefficient in flurothyl-induced status epilepticus in rats. Magn Reson Med 33:253-6
Prichard, J W (1994) Nuclear magnetic resonance spectroscopy of seizure states. Epilepsia 35 Suppl 6:S14-20
Behar, K L; Rothman, D L; Spencer, D D et al. (1994) Analysis of macromolecule resonances in 1H NMR spectra of human brain. Magn Reson Med 32:294-302
Rothman, D L; Petroff, O A; Behar, K L et al. (1993) Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A 90:5662-6
Prichard, J W (1993) The ischemic penumbra in stroke: prospects for analysis by nuclear magnetic resonance spectroscopy. Res Publ Assoc Res Nerv Ment Dis 71:153-74
Graham, G D; Petroff, O A; Blamire, A M et al. (1993) Proton magnetic resonance spectroscopy in Creutzfeldt-Jakob disease. Neurology 43:2065-8
Zhong, J; Petroff, O A; Prichard, J W et al. (1993) Changes in water diffusion and relaxation properties of rat cerebrum during status epilepticus. Magn Reson Med 30:241-6
Petroff, O A; Pleban, L; Prichard, J W (1993) Metabolic assessment of a neuron-enriched fraction of rat cerebrum using high-resolution 1H and 13C NMR spectroscopy. Magn Reson Med 30:559-67
Petroff, O A; Novotny, E J; Avison, M et al. (1992) Cerebral lactate turnover after electroshock: in vivo measurements by 1H/13C magnetic resonance spectroscopy. J Cereb Blood Flow Metab 12:1022-9

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