The goal of this project is to determine the metabolic disturbances within tissue produced by disease and therapy. High- energy phosphates, pH, lactate, and other metabolites will be measured in surface tumors, heart, and kidneys of human patients, using 31P and 1H NHR. Both Bo and B1 localization techniques will be developed, simulated, tested on phantoms, normal subjects, and patients. Cancer studies will examine the possibility that metabolic changes are a sensitive and early index of the response to therapy. These studies will begin with large superficial squamous cell carcinomas of the head and neck. After completing a survey to characterize metabolic composition, heterogeneity, and variability, pilot experiments will determine the effects and time course of chemo- and radiation therapy. A prospective trial will correlate the spectral changes with the ultimate response to therapy, determined by MRI, CT, and ultimate outcome. Heart studies are designed to test the hypothesis that disorders of cardiac energy metabolism may be responsible for functional abnormalities in cardiac disease. 31P and 1H NMR studies of coronary ischemia in the pig will be continued using surgically implanted coils. Spectral localization techniques will be developed using the pig and human subjects. The effects of exercise and pacing will be determined and the metabolic alterations produced by myocardiopathy, hypertrophy, transplant rejection, and ischemia will be examined. Human kidney studies are aimed at investigating the metabolic changes produced by acute tubular necrosis. Once localization techniques are developed, and the normal kidney is examined, the changes associated with acute tubular necrosis will be characterized. Renal function will be correlated with NMR results to determine if spectral changes predict the outcome, or the response to therapy in a series of patients with ATN.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033293-06
Application #
3231679
Study Section
(SSS)
Project Start
1984-09-30
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Higuchi, T; Graham, S H; Fernandez, E J et al. (1997) Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain. Magn Reson Med 37:851-7
Ebisu, T; Rooney, W D; Graham, S H et al. (1996) MR spectroscopic imaging and diffusion-weighted MRI for early detection of kainate-induced status epilepticus in the rat. Magn Reson Med 36:821-8
Hugg, J W; Maudsley, A A; Weiner, M W et al. (1996) Comparison of k-space sampling schemes for multidimensional MR spectroscopic imaging. Magn Reson Med 36:469-73
Miller, R G; Carson, P J; Moussavi, R S et al. (1995) Factors which influence alterations of phosphates and pH in exercising human skeletal muscle: measurement error, reproducibility, and effects of fasting, carbohydrate loading, and metabolic acidosis. Muscle Nerve 18:60-7
Meyerhoff, D J; MacKay, S; Sappey-Marinier, D et al. (1995) Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites. Alcohol Clin Exp Res 19:685-92
Ebisu, T; Rooney, W D; Graham, S H et al. (1994) N-acetylaspartate as an in vivo marker of neuronal viability in kainate-induced status epilepticus: 1H magnetic resonance spectroscopic imaging. J Cereb Blood Flow Metab 14:373-82
Husted, C A; Matson, G B; Adams, D A et al. (1994) In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging. Ann Neurol 36:239-41
Husted, C A; Duijn, J H; Matson, G B et al. (1994) Molar quantitation of in vivo proton metabolites in human brain with 3D magnetic resonance spectroscopic imaging. Magn Reson Imaging 12:661-7
Maudsley, A A; Matson, G B; Hugg, J W et al. (1994) Reduced phase encoding in spectroscopic imaging. Magn Reson Med 31:645-51
Husted, C A; Goodin, D S; Hugg, J W et al. (1994) Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging. Ann Neurol 36:157-65

Showing the most recent 10 out of 38 publications