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 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 its 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 #
5R01NS021708-10
Application #
2264246
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Project Start
1985-07-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Yale University
Department
Neurology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Prichard, J W (1999) New NMR measurements in epilepsy. General introduction, functional magnetic resonance imaging, magnetic resonance spectroscopy, and diffusion-weighted imaging. Adv Neurol 79:917-24
Hwang, J H; Graham, G D; Behar, K L et al. (1996) Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain. Magn Reson Med 35:633-9
Graham, G D; Kalvach, P; Blamire, A M et al. (1995) Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction. Stroke 26:225-9
Prichard, J W; Zhong, J; Petroff, O A et al. (1995) Diffusion-weighted NMR imaging changes caused by electrical activation of the brain. NMR Biomed 8:359-64
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
Novotny Jr, E J; Avison, M J; Herschkowitz, N et al. (1995) In vivo measurement of phenylalanine in human brain by proton nuclear magnetic resonance spectroscopy. Pediatr Res 37:244-9
Prichard, J W (1994) Nuclear magnetic resonance spectroscopy of seizure states. Epilepsia 35 Suppl 6:S14-20
Graham, G D; Zhong, J; Petroff, O A et al. (1994) BOLD MRI monitoring of changes in cerebral perfusion induced by acetazolamide and hypercarbia in the rat. Magn Reson Med 31:557-60
Blamire, A M; Graham, G D; Rothman, D L et al. (1994) Proton spectroscopy of human stroke: assessment of transverse relaxation times and partial volume effects in single volume steam MRS. Magn Reson Imaging 12:1227-35
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

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