multiple sclerosis, arthritis, clinical trials of treatment re- sponse for superficial tumors and breast cancer. The ability to make use of the latest trials of treatment response for superfi- cial tumors and breast cancer. The ability to make use of the latest technology and to apply that in studies which include evaluations in patients is vital for advancing the bounds of patient care and disease management. At UCSF, we are in a strong position to perform such evaluations as we have the necessary MR specialists, clinical expertise and research fa- cilities. We are looking to the Shared Instrumentation Pro- gram to assist us in obtaining the funding which will enable us to purchase the equipment necessary to allow these re- search programs to take advantage of the latest technology. The equipment requested is a prerequisite we need for utiliz- ing the matching commitment from the Department of Radi- ology, which include improved gradients and an Advanced Development Workstation. These upgrades are essential to the long term viability of the research programs at the MRSC and for allowing the experimental techniques which are being developed to progress into clinical practice.

Thesaurus Terms: biomedical equipment purchase, clinical biomedical equipment, computer processing of clinical data, digital imaging, image processing, magnetic resonance imag- ing, nuclear magnetic resonance spectroscopy bioimaging / biomedical imaging

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

IRG:

University Of California San Francisco

500 Parnassus Ave San Francisco, CA 94143 1999 Radiology 15-Apr-99 14-Apr-00 National Center For Research

Resources ZRG1

~ROJECT TITLE

ANNUAL SYMPOSIUM Grant Number: 5P41RR02584-120028 PI Name: Malloy, Craig R.

~ROJECT TITLE

Abstract: A major effort of the training and dissemination aspects of the BRTP grant is our annual NMR symposium. This year's symposium was titled "Symposium and Training VI: 13C in Metabolic Research" and was held at UT South- western on May 7, 1998. The program was aimed at faculty, fellows, and students who are using or considering 13C NMR or 13C mass spectrometry for metabolic studies. The morn- ing training session was an introduction to 13C NMR iso- topomer analysis, factors in experimental design and interpre- tation, analysis of 13C NMR spectra, and an informal time in

which symposium attendees could briefly present and discuss their data. In the afternoon session, the guest faculty focused on 13C NMR and 13C Mass Spectrometry in metabolic re- search with an emphasis on analysis of kinetics. The recep- tion and dinner provided a time for interaction between the attendees and speakers. After dinner, Dr. Robert Shulman discussed his lab's recent metabolic studies in the human brain. A list of the speakers is provided in the Summary of Research Progress. Brochures describing the symposium were sent to potential attendees and a symposium brochure is included in the appendix materials. The Symposium was at- tended by more than 70 people, with attendees primarily from Texas, but several coming from Florida, Georgia, Massachu- setts, Missouri, and Tennessee. A copy of the Symposium handout supplied to the attendees is included in the Appen- dix. Support for the Symposium is obtained from registration fees, corporate sponsors, and the Department of Radiology. The support received is included in OTHER FUNDS on the Resource Summary page. This support covered the dinner and reception. BRTP funds were used for staff support in the organization of the Symposium and to support the travel costs of members of our External Advisory Committee. (Training 2) REPORT PERIOD: (09/01/97-08/31/98)

Thesaurus Terms: biomedical resource, education, magnetic resonance imaging, nuclear magnetic resonance spectroscopy, technology/technique bioimaging/biomedical imaging

Institution: University Of Texas SW Med Ctr/Dallas Southwestern Medical Ctr/ Dallas

Dallas, TX 75390 Fiscal Year: 1999 Department: Radiology Project Start: 30-Sep-85 Project End: 14-Aug-01 ICD: National Center For Research

Resources IRG: ZRG7

IN VlVO 13C & 1H NMR ISOTOPOMER ANALYSIS

Grant Number: 5P41RR02584-120001 PI Name: Malloy, Craig R.

Abstract: We have continued the development of 13C NMR isotopomer methods for diagnostic applications. Significant advances include the first use of HMQC-TOCSY for mea- surement of anaplerosis and substrate oxidation, the first ap- plication of HMQC-TOCSY for quantitation of citric acid cycle kinetics from tissue extracts, and the demonstration that high quality 13C NMR spectra suitable for isotopomer analy- sis can be obtained in humans from urinary phenylacetyl-

993

glutamine, acetaminophen glucuronide or blood glucose. A broad range of problems related to hepatic intermediary me- tabolism which previously could be addressed only with ra- diotracers can now be handled with stable isotopes. (Core 2) REPORT PERIOD: (09/01/97-08/31/98)

Thesaurus Terms: Mammalia, biological product, biomedi- cal resource, cardiovascular system, computer, liver, nuclear magnetic resonance spectroscopy, statistics/biometry, tech- nology/technique human tissue

Institution: University Of Texas SW Med Ctr/Dallas Southwestern Medical Ctr/ Dallas Dallas, TX 75390

Fiscal Year: 1999 Department: Radiology Project Start: 30-Sep-85 Project End: 14-Aug-01 ICD: National Center For Research

Resources IRG: ZRG7

contribution of glucose to oxidative energy production re- mained modest. In contrast, oxidation of lactate and pyruvate was stimulated by hypertrophy to the extent that their me- tabolism provided most of the energy production even at physiological concentrations. (Service 9) REPORT PERIOD: (09/01/97-08/31/98)

Thesaurus Terms: Mammalia, biomedical resource, cardio- vascular system, nuclear magnetic resonance spectroscopy, technology/technique animal tissue

Institution: University Of Texas SW Med Ctr/Dallas Southwestern Medical Ctr/ Dallas Dallas, TX 75390

Fiscal Year: 1999 Department: Radiology Project Start: 30-Sep-85 Project End: 14-Aug-01 ICD: National Center For Research

Resources IRG: ZRG7

~ROJECT TITLE ~ROJECT TITLE

INTERMEDIARY METABOLISM & CATIONS BY NMR

Grant Number: 5P41RR02584-120020 PI Name: Malloy, Craig R.

Abstract: We continue to apply 13C NMR methods for analysis of metabolism in the isolated rat heart. Over the last year one target has been analysis of metabolism in hypertro- pkied heart tissue. Earlier studies indicated that energy pro- duction from exogenous fatty acids or carbohydrates and from endogenous energy stores may be substantially dis- rupted in left ventricular hypertrophy. The contribution of long chain fatty acids (0.35 mM), lactate (1.2 mM), pyruvate (0.09 raM), glucose (5.5 raM), acetoacetate (0.12 raM), a- hydroxybutyrate (0.05 mM), and endogenous sources to en- ergy production was determined by 13C NMR isotopomer analysis in two standard models of left ventricular hypertro- phy, the spontaneously hypertensive rat and the aortic banded Sprague-Dawley rat. The fraction of acetyl-CoA derived from various sources was not different between the two con- trol groups: fatty acids, 0.46-0.56; lactate plus pyruvate, 0.25-0.32; ketones, 0.11-0.12, glucose, 0.03-0.05: and endog- enous sources, 0.03-0.06. However, oxidation of fatty acids was significantly decreased in spontaneously hypertensive rats (0.20 q 0.02 of acetyl-CoA production, mean q s.d.) or in banded Sprague-Dawley rats (0.24 q 0.04 of acetyl-CoA pro- duction). Ketone and octanoate oxidation was unaffected by hypertrophy. Oxidation of glucose and glycolysis was in- creased in both models of pressure overload, but the overall

SOUTHWESTERN BIOMEDICAL MAGNETIC RESONANCE FACILITY

Grant Number: 5P41RR02584-12 PI Name: Malloy, Craig R.

Abstract: NMR and mass spectrometry methods will be de- veloped in 3 core research projects. Studies in Core 1 will test new 2D NMR and decoupling techniques as well as other methods to develop very high sensitivity. 13/C NMR isotopo- mer analysis. These methods have fundamental advantages over conventional tracer studies, and as such are broadly ap- plicable to diverse biological questions and animal models. The specific target is to establish protocols for quantitation of fluxes through key pathways involved with gluconeogenesis, glycogenolysis and fatty acid oxidation in the human liver by analysis of 13/C in metabolic products in blood and urine. These procedures have potential for rapid translation to clini- cal research in numerous institutions. In Core 2 computa- tional methods will be expanded to integrate all forms of 13/ C isotopomer data (2D NMR, mass spectroscopy and tandem mass spectrometry), and more complex problems in isotopo- mer analysis will be investigated. Core 3 will extend our ca- pabilities of monitoring biological cations. Superior 23/Na NMR shift agents and new ligands to monitor divalent cat- ions will be a high priority. The Facility has added a 600 MHz NMR spectrometer in the last few months, and the ex- isting 300 MHs and 500 MHz systems have been upgraded. The Facility will support 5 NMR spectroscopy/imaging sys- tems at two universities. Multiple independent investigators

994