title: Detection of inflammatory arthritis by using hyperpolarized 13C-pyruvate with MR imaging and spectroscopy.
abstract: OBJECTIVE
  To examine the feasibility of using magnetic resonance (MR) spectroscopy with hyperpolarized carbon 13 ((13)C)-labeled pyruvate to detect inflammation.
  
  
  METHODS
  The animal care and use committee approved all work with animals. Arthritis was induced in the right hind paw of six rats; the left hind paw served as an internal control. The lactate dehydrogenase-catalyzed conversion of pyruvate to lactate was measured in inflamed and control paws by using (13)C MR spectroscopy. Clinical and histologic data were obtained to confirm the presence and severity of arthritis. Hyperpolarized (13)C-pyruvate was intravenously injected into the rats before simultaneous imaging of both paws with (13)C MR spectroscopy. The Wilcoxon signed rank test was used to test for differences in metabolites between the control and arthritic paws.
  
  
  RESULTS
  All animals showed findings of inflammation in the affected paws and no signs of arthritis in the control paws at both visible inspection (clinical index of 3 for arthritic paws and 0 for control paws) and histologic examination (histologic score of 3-5 for arthritic paws and 0 for control paws). Analysis of the spectroscopic profiles of (13)C-pyruvate and converted (13)C-lactate showed an increase in the amount of (13)C-lactate in inflamed paws (median lactate-to-pyruvate ratio, 0.50; mean lactate-to-pyruvate ratio ± standard deviation, 0.52 ± 0.16) versus control paws (median lactate-to-pyruvate ratio, 0.27; mean lactate-to-pyruvate ratio, 0.32 ± 0.11) (P < .03). The ratio of (13)C-lactate to total (13)C was also significantly increased in inflamed paws compared with control paws (P < .03).
  
  
  CONCLUSIONS
  These results suggest that alterations in the conversion of pyruvate to lactate as detected with (13)C-MR spectroscopy may be indicative of the presence of inflammatory arthritis.
authors.affiliation: Department of Radiology, Stanford University, Stanford, Calif, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: MacKenzie
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: James S
authors.initials: JS
authors.lastname: Tropp
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002247:Carbon Isotopes / Q000378:metabolism; D003287:Contrast Media / Q000378:metabolism; D004195:Disease Models, Animal; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000378:metabolism; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D009942:Organometallic Compounds / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D002247:Carbon Isotopes; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D011773:Pyruvates; C062402:gadoteridol; D019344:Lactic Acid; D005682:Gadolinium