In vivo carbon-13 dynamic MRS and MRSI of normal and fasted rat liver with hyperpolarized 13C-pyruvate.
BACKGROUND
The use of in vivo (13)C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active (13)C substrates, allowing for rapid assessment of (13)C metabolism in vivo. The present study applied hyperpolarized (13)C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states.


METHODS
[1-(13)C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI).


RESULTS
Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased (13)C-alanine levels (P < 0.01) compared to normal.


CONCLUSIONS
This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology.
Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158-2512, USA.
Simon
S
Hu
Albert P
AP
Chen
Matthew L
ML
Zierhut
Robert
R
Bok
Yi-Fen
YF
Yen
Marie A
MA
Schroeder
Ralph E
RE
Hurd
Sarah J
SJ
Nelson
John
J
Kurhanewicz
Daniel B
DB
Vigneron
D000409:Alanine / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D005215:Fasting; D005240:Feasibility Studies; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation* / Q000379:methods*; D008297:Male; D008954:Models, Biological; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid; D000409:Alanine