Effects of isoflurane anesthesia on hyperpolarized (13)C metabolic measurements in rat brain

Magn Reson Med. 2013 Oct;70(4):1117-24. doi: 10.1002/mrm.24532. Epub 2012 Oct 19.

Abstract

Purpose: Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose-dependent increase in cerebral blood flow and cerebral blood volume. Despite the widespread use of isoflurane in hyperpolarized (13)C preclinical research studies, a quantitative assessment of its effect on metabolic measurements is limited. This work investigates the effect of isoflurane anesthesia dose on hyperpolarized (13)C MR metabolic measurements in rat brain for [1-(13)C]pyruvate and 2-keto[1-(13)C]isocaproate.

Methods: Dynamic 2D and 3D spiral chemical shift imaging was used to acquire metabolic images of rat brain as well as kidney and liver following bolus injections of hyperpolarized [1-(13)C]pyruvate or 2-keto[1-(13)C]isocaproate. The impact of a "low dose" vs. a "high dose" of isoflurane on cerebral metabolite levels and apparent conversion rates was examined.

Results: The cerebral substrate signal levels, and hence the metabolite-to-substrate ratios and apparent conversion rates, were found to depend markedly on isoflurane dose, while signal levels of metabolic products and their ratios, e.g. bicarbonate/lactate, were largely insensitive to isoflurane levels. No obvious dependence on isoflurane was observed in kidney or liver for pyruvate.

Conclusion: This study highlights the importance of careful attention to the effects of anesthesia on the metabolic measures for hyperpolarized (13)C metabolic imaging in brain.

Keywords: anesthesia; brain; hyperpolarized 13C; isoflurane; metabolic imaging; metabolite ratios.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Anesthetics, Inhalation / administration & dosage
  • Animals
  • Artifacts
  • Brain / drug effects*
  • Brain / metabolism*
  • Caproates / metabolism*
  • Carbon Isotopes / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Isoflurane / administration & dosage*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Metabolic Clearance Rate / drug effects
  • Pyruvic Acid / metabolism*
  • Rats
  • Rats, Wistar
  • Tissue Distribution / drug effects

Substances

  • Anesthetics, Inhalation
  • Caproates
  • Carbon Isotopes
  • isocaproic acid
  • Pyruvic Acid
  • Isoflurane