This application is for the purchase of a Hypersense Dynamic Nuclear Polarizer (DNP) instrument which is already on loan and sited in the Advanced Imaging Research Center in close proximity to a narrow bore 600MHz NMR spectrometer. A common goal of the investigators in the center is the study of metabolic fluxes using 13C isotopomer analysis. Different incarnations of the isotopomer analysis method have been used to study perfused organs and cells as well as mice, rats, and humans. A variety of metabolic pathways have been assayed as well, including the Kreb's cycle, gluconeogenesis and glycogenolysis, b-oxidation, ketogenesis, etc. Often, the studies are carried out on extracts of blood drawn from the subject. ? ? Common to all these applications is a need for enhanced sensitivity for 13C NMR studies. Currently, two 14.1Tesla magnets are dedicated to metabolic studies at UT Southwestern. Even with the outstanding hardware available, survival experiments on mice and rats are not feasible due to the quantity of metabolite needed to acquire the 13C spectra in a reasonable amount of time. In most mouse studies, blood from two to three animals must be pooled to isolate single metabolites for NMR analysis. With the addition of the Hypersense technology, survival experiments for mice should be attainable at the very least. Hypersense has the potential for 10000 time gains in sensitivity for NMR, transforming the range of applications for isotopomer analysis. Perhaps even more importantly, the Hypersense has already demonstrated the ability to elucidate metabolic flux in perfused organs. Real time measurements of bicarbonate production and Kreb's cycle turnover have already been made in rat hearts. ? ? Hypersense DNP is a fundamental change in the sensitivity for NMR experiments. Integration of this technology into research already underway promises a quantum leap in the power of 13C isotopomer analysis. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR024592-01
Application #
7390180
Study Section
Special Emphasis Panel (ZRG1-SBIB-N (30))
Program Officer
Tingle, Marjorie
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
1
Fiscal Year
2008
Total Cost
$421,000
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Lumata, Lloyd L; Merritt, Matthew E; Malloy, Craig R et al. (2013) Dissolution DNP-NMR spectroscopy using galvinoxyl as a polarizing agent. J Magn Reson 227:14-9
Lumata, Lloyd; Kovacs, Zoltan; Sherry, A Dean et al. (2013) Electron spin resonance studies of trityl OX063 at a concentration optimal for DNP. Phys Chem Chem Phys 15:9800-7
Lumata, Lloyd; Merritt, Matthew E; Kovacs, Zoltan (2013) Influence of deuteration in the glassing matrix on 13C dynamic nuclear polarization. Phys Chem Chem Phys 15:7032-5
Lumata, Lloyd; Merritt, Matthew E; Malloy, Craig R et al. (2012) Impact of Gd3+ on DNP of [1-13C]pyruvate doped with trityl OX063, BDPA, or 4-oxo-TEMPO. J Phys Chem A 116:5129-38
Lumata, Lloyd; Merritt, Matthew E; Hashami, Zohreh et al. (2012) Production and NMR characterization of hyperpolarized (107,109)Ag complexes. Angew Chem Int Ed Engl 51:525-7
Harrison, Crystal; Yang, Chendong; Jindal, Ashish et al. (2012) Comparison of kinetic models for analysis of pyruvate-to-lactate exchange by hyperpolarized 13 C NMR. NMR Biomed 25:1286-94
Lumata, Lloyd; Merritt, Matthew; Khemtong, Chalermchai et al. (2012) The efficiency of DPPH as a polarising agent for DNP-NMR spectroscopy. RSC Adv 2:12812-12817
Lumata, Lloyd; Kovacs, Zoltan; Malloy, Craig et al. (2011) The effect of 13C enrichment in the glassing matrix on dynamic nuclear polarization of [1-13C]pyruvate. Phys Med Biol 56:N85-92
Lumata, Lloyd; Jindal, Ashish K; Merritt, Matthew E et al. (2011) DNP by thermal mixing under optimized conditions yields >60,000-fold enhancement of 89Y NMR signal. J Am Chem Soc 133:8673-80
Merritt, Matthew E; Harrison, Crystal; Sherry, A Dean et al. (2011) Flux through hepatic pyruvate carboxylase and phosphoenolpyruvate carboxykinase detected by hyperpolarized 13C magnetic resonance. Proc Natl Acad Sci U S A 108:19084-9

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