National Center for In Vivo Metabolism (EB015908) This application proposes to renew a Biomedical Technology Research Centers (BTRC) focused on the use of stable isotopes to probe metabolism in human patients. The BTRC is motivated by the strong current interest in disruptions of intermediary metabolism in high impact conditions such as nonalcoholic fatty liver disease, cancer, congestive heart failure, diabetes and others. Although we have considerable knowledge from animal and cell models about metabolic pathways, little of this information can be used for clinical research and direct patient care because the information yield from traditional metabolic studies such as PET is so poor. Stable isotopes with detection of metabolic products by NMR are attractive because of the inherently rich information content of these exams which is far superior to alternatives. The poor inherent sensitivity of NMR is the critical obstacle to clinical translation. One solution is analysis of tissue biopsies and blood samples in high resolution analytical systems, an approach pioneered in this BTRC. Another solution is imaging and spectroscopy of hyperpolarized nuclei. There are a number of major opportunities to help translation of this technology to the clinic, including better 15N and 13C probes, improved software for simulation and data analysis, improved integration of NMR and mass spectrometry data, implementation of hyperpolarization exams in human patients, and validation of hyperpolarization results. We propose coordinated development of technologies focused on in vivo exams. Three technology research and development projects are planned, all driven by specific needs of our collaborative users. In TR&D 1, we will develop new probes tailored for 15N and 13C hyperpolarization and provide the infrastructure to understand the biological value of these probes. In TR&D 2, we will develop integrated methods for combining data from mass spectrometry and NMR spectroscopy exams, with the purpose of probing metabolism in small, biopsy- sized tissue samples. TR&D 3 will focus on in vivo applications of 13C NMR and creation of an infrastructure for hyperpolarization studies in human patients. The capacity to investigate imaging and spectroscopy of hyperpolarized nuclei is limited to a small handful of centers in the nation. The ability to integrate conventional analytical NMR and mass spectrometry methods with hyperpolarization exams is even less accessible. This program will leverage extraordinary institutional support for space, equipment and personnel in a combined basic research and clinical environment. This diverse user group, including the physicians, share one commonality in having a long track record of metabolic studies using conventional NMR and mass spectrometry for examining metabolism. The Center will retain its exclusive focus on metabolism and continue efforts in training young scientists.

Public Health Relevance

National Center for In Vivo Metabolism (EB015908) All high-impact diseases are associated with abnormal fluxes in biochemical pathways. We have a great deal of knowledge about metabolism in disease, based on animal and cell experiments, yet little of that information can actually be used in management of an individual patient because of limitations in technology. Our purpose is to provide personalized metabolic exams in patients. The methods offer significant advantages compared to current studies: superior information about biochemical pathways, absence of ionizing radiation, and simple integration with standard imaging methods.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZEB1)
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Wang, Shumin
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University of Texas Sw Medical Center Dallas
Internal Medicine/Medicine
Schools of Medicine
United States
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Park, Jae Mo; Wu, Marvin; Datta, Keshav et al. (2017) Hyperpolarized Sodium [1-13C]-Glycerate as a Probe for Assessing Glycolysis In Vivo. J Am Chem Soc 139:6629-6634
Zhang, Lei; Martins, André F; Zhao, Piyu et al. (2017) Enantiomeric Recognition of d- and l-Lactate by CEST with the Aid of a Paramagnetic Shift Reagent. J Am Chem Soc 139:17431-17437
Tiwari, Vivek; An, Zhongxu; Ganji, Sandeep K et al. (2017) Measurement of glycine in healthy and tumorous brain by triple-refocusing MRS at 3 T in vivo. NMR Biomed 30:
Lin, Gigin; Keshari, Kayvan R; Park, Jae Mo (2017) Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy. Contrast Media Mol Imaging 2017:6053879
Neeland, Ian J; Hughes, Connor; Ayers, Colby R et al. (2017) Effects of visceral adiposity on glycerol pathways in gluconeogenesis. Metabolism 67:80-89
Zhang, Lei; Evbuomwan, Osasere M; Tieu, Michael et al. (2017) Protonation of carboxyl groups in EuDOTA-tetraamide complexes results in catalytic prototropic exchange and quenching of the CEST signal. Philos Trans A Math Phys Eng Sci 375:
Zhou, Heling; Zhang, Zhang; Denney, Rebecca et al. (2017) Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging. Oncotarget 8:37464-37477
Marco-Rius, Irene; von Morze, Cornelius; Sriram, Renuka et al. (2017) Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-13 C]dihydroxyacetone. Magn Reson Med 77:65-73
Funk, Alexander M; Anderson, Brian L; Wen, Xiaodong et al. (2017) The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose. J Magn Reson 284:86-93
Marco-Rius, Irene; Cao, Peng; von Morze, Cornelius et al. (2017) Multiband spectral-spatial RF excitation for hyperpolarized [2-13 C]dihydroxyacetone 13 C-MR metabolism studies. Magn Reson Med 77:1419-1428

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