31P-Magnetization Transfer Magnetic Resonance Spectroscopy Measurements of In Vivo Metabolism

  1. Gerald I. Shulman2,4,5
  1. 1Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
  2. 2Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
  3. 3Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut
  4. 4Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut
  5. 5Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut
  1. Corresponding author: Douglas E. Befroy, douglas.befroy{at}yale.edu.

Abstract

Magnetic resonance spectroscopy offers a broad range of noninvasive analytical methods for investigating metabolism in vivo. Of these, the magnetization-transfer (MT) techniques permit the estimation of the unidirectional fluxes associated with metabolic exchange reactions. Phosphorus (31P) MT measurements can be used to examine the bioenergetic reactions of the creatine-kinase system and the ATP synthesis/hydrolysis cycle. Observations from our group and others suggest that the inorganic phosphate (Pi) → ATP flux in skeletal muscle may be modulated by certain conditions, including aging, insulin resistance, and diabetes, and may reflect inherent alterations in mitochondrial metabolism. However, such effects on the Pi → ATP flux are not universally observed under conditions in which mitochondrial function, assessed by other techniques, is impaired, and recent articles have raised concerns about the absolute magnitude of the measured reaction rates. As the application of 31P-MT techniques becomes more widespread, this article reviews the methodology and outlines our experience with its implementation in a variety of models in vivo. Also discussed are potential limitations of the technique, complementary methods for assessing oxidative metabolism, and whether the Pi → ATP flux is a viable biomarker of metabolic function in vivo.

  • Received April 30, 2012.
  • Accepted July 11, 2012.

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