In Vivo Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized 13C-Pyruvate

UCSF & UCB Joint Graduate Group in Bioengineering Berkeley CA USA
Molecular Imaging & Biology (Impact Factor: 2.77). 11/2009; 11(6):399-407. DOI: 10.1007/s11307-009-0218-z
Source: PubMed


The use of in vivo13C 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 13C substrates, allowing for rapid assessment of 13C metabolism in vivo. The present study applied hyperpolarized 13C 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.

[1-13C]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).

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 13C-alanine levels (P < 0.01) compared to normal.

This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized 13C 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.

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    • "In previous studies where hyperpolarized [1- 13 C]pyruvate was used as a substrate, a decrease in the 13 C alanine signal was observed in a perfused liver model and in the liver in vivo after a fasting period and this reduction was ascribed to a cellular redox state change and a reduction in ALT activity respectively (Merritt et al. 2011; Hu et al. 2009). However, a direct comparison with results obtained using pyruvate as a hyperpolarized substrate is challenging since different metabolite pools are enriched and the reaction pathways and directions probed are different. "
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