Support is requested to purchase a rampable clinical MRI system, 1.5 to 3.0 T, equipped for 13C chemical shift imaging of hyperpolarized molecules as reporters of flux through specific metabolic pathways in the human heart. UT Southwestern has a long record of research in 13C NMR spectroscopy for analysis of intermediary metabolism in the heart and, more recently, a productive research program in 13C dynamic nuclear polarization (DNP) has been established. Even at this early stage of development, it is clear that 13C DNP offers fundamentally new insights into physiology and disease models in animals and there is little doubt that the technology will be applicable in human patients with heart disease. Current research programs at Southwestern, however, are limited by the lack of a flexible MR instrument suitable for developing in vivo 13C imaging studies. The proposed scanner will be installed at the Advanced Imaging Research Center and integrated with the existing research program in DNP. The immediate goal is to image hyperpolarized 13C in the heart and liver of rodents and larger animals to establish the basis for clinical trials in humans. This facility will be unique because of the combined local expertise in molecular biology, metabolism, synthetic chemistry, 13C NMR spectroscopy, and cardiology. UT Southwestern does not receive industry support for studies with hyperpolarized nuclei nor do we have intellectual property agreements with any company related to production or applications of hyperpolarized nuclei. Consequently, we are free to explore DNP as judged appropriate. Dynamic nuclear polarization has the potential to fundamentally transform molecular imaging for clinical exams.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR029119-01
Application #
7842399
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (31))
Program Officer
Birken, Steven
Project Start
2011-09-16
Project End
2014-03-15
Budget Start
2011-09-16
Budget End
2014-03-15
Support Year
1
Fiscal Year
2011
Total Cost
$2,237,277
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
Wang, Jian-Xiong; Merritt, Matthew E; Sherry, A Dean et al. (2016) Accelerated chemical shift imaging of hyperpolarized (13) C metabolites. Magn Reson Med 76:1033-8
Malloy, Craig R; Sherry, A Dean (2016) Biochemical Specificity in Human Cardiac Imaging by 13C Magnetic Resonance Imaging. Circ Res 119:1146-1148
Jin, Eunsook S; Moreno, Karlos X; Wang, Jian-Xiong et al. (2016) Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver. NMR Biomed 29:466-74
Wang, Jian-Xiong; Merritt, Matthew E; Sherry, Dean et al. (2016) A general chemical shift decomposition method for hyperpolarized (13) C metabolite magnetic resonance imaging. Magn Reson Chem 54:665-73
Bankson, James A; Walker, Christopher M; Ramirez, Marc S et al. (2015) Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors. Cancer Res 75:4708-17
Buescher, Joerg M; Antoniewicz, Maciek R; Boros, Laszlo G et al. (2015) A roadmap for interpreting (13)C metabolite labeling patterns from cells. Curr Opin Biotechnol 34:189-201