Real-time Metabolic Imaging

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jul 14

PMID 16837573

Citations 311

Authors

Klaes Golman

Rene In t Zandt

Mikkel Thaning

Affiliations

Soon will be listed here.

Abstract

The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10-15% polarization of (13)C(1) in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of approximately 10 s. Real-time molecular imaging with MRI has become a reality.

Citing Articles

Metabolic PCTA-Based Shift Reagents for the Detection of Extracellular Lactate Using CEST MRI.

Chiaffarelli R, Cruz P, Cotton J, Kelm T, Lee S, Ghaderian M JACS Au. 2025; 5(2):779-790.

PMID: 40017765 PMC: 11862947. DOI: 10.1021/jacsau.4c01020.

Simultaneous noninvasive quantification of redox and downstream glycolytic fluxes reveals compartmentalized brain metabolism.

Patel S, Porcari P, Coffee E, Kim N, Berishaj M, Peyear T Sci Adv. 2024; 10(51):eadr2058.

PMID: 39705365 PMC: 11661454. DOI: 10.1126/sciadv.adr2058.

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

Ariyasingha N, Samoilenko A, Chowdhury M, Nantogma S, Oladun C, Birchall J Chem Biomed Imaging. 2024; 2(10):698-710.

PMID: 39483636 PMC: 11523004. DOI: 10.1021/cbmi.4c00041.

Enhanced Solubility and Polarization of C-Fumarate with Meglumine Allows for In Vivo Detection of Gluconeogenic Metabolism in Kidneys.

Huynh M, Erfani Z, Al Nemri S, Chirayil S, Kovacs Z, Park J ACS Appl Mater Interfaces. 2024; 16(29):37435-37444.

PMID: 38984763 PMC: 11272437. DOI: 10.1021/acsami.4c03163.

Detection of early-stage NASH using non-invasive hyperpolarized C metabolic imaging.

von Morze C, Blazey T, Shaw A, Spees W, Shoghi K, Ohliger M Sci Rep. 2024; 14(1):14854.

PMID: 38937567 PMC: 11211431. DOI: 10.1038/s41598-024-65951-z.

References

Morikawa S, Inubushi T . Fast (13)C-glucose metabolite mapping in rat brain using (1)H echo planar spectroscopic imaging technique at 2T. J Magn Reson Imaging. 2001; 13(5):787-91. DOI: 10.1002/jmri.1109. View

Mansson S, Johansson E, Magnusson P, Chai C, Hansson G, Petersson J . 13C imaging-a new diagnostic platform. Eur Radiol. 2006; 16(1):57-67. DOI: 10.1007/s00330-005-2806-x. View

Naressi A, Couturier C, Devos J, Janssen M, Mangeat C, de Beer R . Java-based graphical user interface for the MRUI quantitation package. MAGMA. 2001; 12(2-3):141-52. DOI: 10.1007/BF02668096. View

Vanhamme L, SUNDIN T, Hecke P, Huffel S . MR spectroscopy quantitation: a review of time-domain methods. NMR Biomed. 2001; 14(4):233-46. DOI: 10.1002/nbm.695. View

Mongan P, Capacchione J, Fontana J, West S, Bunger R . Pyruvate improves cerebral metabolism during hemorrhagic shock. Am J Physiol Heart Circ Physiol. 2001; 281(2):H854-64. DOI: 10.1152/ajpheart.2001.281.2.H854. View

Bluml S, Moreno-Torres A, Shic F, Ross B . Tricarboxylic acid cycle of glia in the in vivo human brain. NMR Biomed. 2002; 15(1):1-5. DOI: 10.1002/nbm.725. View

Wiechert W . An introduction to 13C metabolic flux analysis. Genet Eng (N Y). 2002; 24:215-38. DOI: 10.1007/978-1-4615-0721-5_10. View

Golman K, Ardenkjaer-Larsen J, Petersson J, Mansson S, Leunbach I . Molecular imaging with endogenous substances. Proc Natl Acad Sci U S A. 2003; 100(18):10435-9. PMC: 193579. DOI: 10.1073/pnas.1733836100. View

Ardenkjaer-Larsen J, Fridlund B, Gram A, Hansson G, Hansson L, Lerche M . Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003; 100(18):10158-63. PMC: 193532. DOI: 10.1073/pnas.1733835100. View

10.

Morris P, Bachelard H . Reflections on the application of 13C-MRS to research on brain metabolism. NMR Biomed. 2003; 16(6-7):303-12. DOI: 10.1002/nbm.844. View

11.

Ross B, Lin A, Harris K, Bhattacharya P, Schweinsburg B . Clinical experience with 13C MRS in vivo. NMR Biomed. 2003; 16(6-7):358-69. DOI: 10.1002/nbm.852. View

12.

Burich R, King V . Pyruvate handling by the intact functioning kidney of the dog. Am J Physiol. 1973; 225(2):389-92. DOI: 10.1152/ajplegacy.1973.225.2.389. View

13.

Baverel G, Bonnard M, PELLET M . Lactate and pyruvate metabolism in isolated human kidney tubules. FEBS Lett. 1979; 101(2):282-6. DOI: 10.1016/0014-5793(79)81026-1. View

14.

Brown T, Kincaid B, Ugurbil K . NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci U S A. 1982; 79(11):3523-6. PMC: 346453. DOI: 10.1073/pnas.79.11.3523. View

15.

Schadewaldt P, Munch U, Prengel M, STAIB W . Estimation of pyruvate decarboxylation in perfused rat skeletal muscle. Biochem Biophys Res Commun. 1983; 116(2):456-61. DOI: 10.1016/0006-291x(83)90545-4. View

16.

Schadewaldt P, Munch U, STAIB W . Evidence for the compartmentation of pyruvate metabolism in perfused rat skeletal muscle. Biochem J. 1983; 216(3):761-4. PMC: 1152572. DOI: 10.1042/bj2160761. View

17.

Sibson N, Dhankhar A, MASON G, Behar K, Rothman D, Shulman R . In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proc Natl Acad Sci U S A. 1997; 94(6):2699-704. PMC: 20152. DOI: 10.1073/pnas.94.6.2699. View

18.

Jucker B, Rennings A, Cline G, Petersen K, Shulman G . In vivo NMR investigation of intramuscular glucose metabolism in conscious rats. Am J Physiol. 1997; 273(1 Pt 1):E139-48. DOI: 10.1152/ajpendo.1997.273.1.E139. View

19.

Oz G, Berkich D, Henry P, Xu Y, LaNoue K, Hutson S . Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci. 2004; 24(50):11273-9. PMC: 6730363. DOI: 10.1523/JNEUROSCI.3564-04.2004. View

20.

Mallet R, Sun J, Marty Knott E, Sharma A, Olivencia-Yurvati A . Metabolic cardioprotection by pyruvate: recent progress. Exp Biol Med (Maywood). 2005; 230(7):435-43. DOI: 10.1177/153537020523000701. View