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)
Project #
Application #
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Wang, Shumin
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Chiu, Tsuicheng D; Arai, Tatsuya J; Campbell Iii, James et al. (2018) MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors. PLoS One 13:e0198065
Xie, Fang; Cai, Huawei; Peng, Fangyu (2018) Anti-prostate cancer activity of 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide copper complexes in vivo by bioluminescence imaging. J Biol Inorg Chem :
Imakura, Yuki; Nonaka, Hiroshi; Takakusagi, Yoichi et al. (2018) Rational Design of [13 C,D14 ]Tert-butylbenzene as a Scaffold Structure for Designing Long-lived Hyperpolarized 13 C Probes. Chem Asian J 13:280-283
Kikuchi, Kazufumi; Ishimatsu, Keisuke; Zhang, Shanrong et al. (2018) Presaturation Power Adjusted Pulsed CEST: A Method to Increase Independence of Target CEST Signals. Contrast Media Mol Imaging 2018:3141789
Garda, Zoltán; Molnár, Enik?; Kálmán, Ferenc K et al. (2018) Effect of the Nature of Donor Atoms on the Thermodynamic, Kinetic and Relaxation Properties of Mn(II) Complexes Formed With Some Trisubstituted 12-Membered Macrocyclic Ligands. Front Chem 6:232
Zhou, Heling; Arias-Ramos, Nuria; López-Larrubia, Pilar et al. (2018) Oxygenation Imaging by Nuclear Magnetic Resonance Methods. Methods Mol Biol 1718:297-313
Jin, Eunsook S; Lee, Min Hee; Murphy, Rebecca E et al. (2018) Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver. Am J Physiol Endocrinol Metab 314:E543-E551
Pérez-Malo, Marylaine; Szabó, Gergely; Eppard, Elisabeth et al. (2018) Improved Efficacy of Synthesizing *MIII-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study. Inorg Chem 57:6107-6117
Yang, Li-Min; Zheng, Hui; Ratnakar, James S et al. (2018) Engineering a pH-Sensitive Liposomal MRI Agent by Modification of a Bacterial Channel. Small 14:e1704256
Wu, Cheng-Yang; Satapati, Santhosh; Gui, Wenjun et al. (2018) A novel inhibitor of pyruvate dehydrogenase kinase stimulates myocardial carbohydrate oxidation in diet-induced obesity. J Biol Chem 293:9604-9613

Showing the most recent 10 out of 149 publications