title: Effects of isoflurane anesthesia on hyperpolarized (13)C metabolic measurements in rat brain.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, California, USA; Department of Radiology, Stanford University, Lucas MRI Center, Stanford, California, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Ralph
authors.initials: R
authors.lastname: Hurd
authors.forename: Kelvin
authors.initials: K
authors.lastname: Billingsley
authors.forename: Lasitha
authors.initials: L
authors.lastname: Senadheera
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D016477:Artifacts; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002208:Caproates / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000008:administration & dosage*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D002208:Caproates; D002247:Carbon Isotopes; C034527:isocaproic acid; D019289:Pyruvic Acid; D007530:Isoflurane
keywords: anesthesia; brain; hyperpolarized 13C; isoflurane; metabolic imaging; metabolite ratios