This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Despite recent advances in molecular biology that have provided a fuller understanding of the transcriptional basis of disease, technology that allows the ultimate end product of transcription, metabolic flux, to be measured in vivo is very limited. The importance of measuring flux is highlighted by a number of examples in animal models where changes in enzyme expression do not match changes in flux through the enzyme. Thus, if the metabolic basis of disease is to be explicitly understood, techniques which measure in vivo fluxes must be further developed so that they can be easily utilized by basic and clinical scientists. NMR isotopomer analysis of small molecule metabolites is well suited to make these measurements because chemical shift and spin-spin coupling allow the isotopomer populations to be very well defined. Knowledge of isotopic distributions in metabolites is tantamount to knowing the flux through the biochemical pathways that generated the isotopomers. The continued focus of Core I is to address technology development for NMR based metabolic analysis with an emphasis on improved sensitivity of NMR isotopomer analysis of in vivo metabolism.
The specific aims are: 1. Multiplexing metabolic flux.
This aim seeks to expand the number of metabolic pathways measured in a single in vivo experiment by incorporating additional13C tracers of hepatic fluxes into the techniques developed in the previous funding cycle.
This aim will improve the experimental efficiency of the NMR isotopomer method (compared to other methods of isotope detection) by making simultaneous measurements of multiple hepatic fluxes. 2. Mathematical analysis of tracer data from complex systems.
Our aim i s to more fully refine the mathematical models that describe hepatic fluxes with respect to parameter sensitivity, experimental design and extend an existing kinetic model from a simple onecompartment tissue model to a more realistic two-compartment model. This will enhance our capabilities to use 13C NMR multiplet data for analysis of liver and brain metabolism as we move toward more in vivo work on our new high field human scanners. 3. Improve NMR detection of 2H and 13C for metabolic studies. To increase the applicability of our metabolic flux measurements, it is essential that we continue to increase the sensitivity of both the 2H and 13C NMR experiments, the backbone of this methodology. We will extend 2H NMR and JHSQC experiments to 18.8T to take advantage of the increased sensitivity and dispersion of the higher magnetic field and develop the necessary methods to take maximum advantage of new micro-solenoidal probes that offer higher sensitivity for sample limited cases. Finally, we will test the suitability of new high temperature superconducting NMR probes for metabolic measurements.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002584-20
Application #
7600831
Study Section
Special Emphasis Panel (ZRG1-SBIB-Q (40))
Project Start
2007-09-01
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
20
Fiscal Year
2007
Total Cost
$302,429
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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
Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus et al. (2017) Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance. Sci Rep 7:11719
Moreno, Karlos X; Harrison, Crystal E; Merritt, Matthew E et al. (2017) Hyperpolarized ?-[1-13 C]gluconolactone as a probe of the pentose phosphate pathway. NMR Biomed 30:
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
Zhang, Liang; Habib, Amyn A; Zhao, Dawen (2016) Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging. Oncotarget 7:38693-38706
Walker, Christopher M; Merritt, Matthew; Wang, Jian-Xiong et al. (2016) Use of a Multi-compartment Dynamic Single Enzyme Phantom for Studies of Hyperpolarized Magnetic Resonance Agents. J Vis Exp :e53607
Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C et al. (2016) pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent. Magn Reson Med 75:2432-41
Malloy, Craig R; Sherry, A Dean (2016) Biochemical Specificity in Human Cardiac Imaging by 13C Magnetic Resonance Imaging. Circ Res 119:1146-1148
Moss, Lacy R; Mulik, Rohit S; Van Treuren, Tim et al. (2016) Investigation into the distinct subcellular effects of docosahexaenoic acid loaded low-density lipoprotein nanoparticles in normal and malignant murine liver cells. Biochim Biophys Acta 1860:2363-2376
Bastiaansen, Jessica A M; Merritt, Matthew E; Comment, Arnaud (2016) Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-(13)C]butyrate and [1-(13)C]pyruvate. Sci Rep 6:25573

Showing the most recent 10 out of 374 publications