Combining hyperpolarized13C MRI with a liver-specific gadolinium contrast agent for selective assessment of hepatocyte metabolism.
Hyperpolarized13C MRI is a powerful tool for studying metabolism, but can lack tissue specificity. Gadoxetate is a gadolinium-based MRI contrast agent that is selectively taken into hepatocytes. The goal of this project was to investigate whether gadoxetate can be used to selectively suppress the hyperpolarized signal arising from hepatocytes, which could in future studies be applied to generate specificity for signal from abnormal cell types.



Baseline gadoxetate uptake kinetics were measured using T1-weighted contrast enhanced imaging. Relaxivity of gadoxetate was measured for [1-13C]pyruvate, [1-13C]lactate, and [1-13C]alanine. Four healthy rats were imaged with hyperpolarized [1-13C]pyruvate using a three-dimensional (3D) MRSI sequence prior to and 15 min following administration of gadoxetate. The lactate:pyruvate ratio and alanine:pyruvate ratios were measured in liver and kidney.



Overall, the hyperpolarized signal decreased approximately 60% as a result of pre-injection of gadoxetate. In liver, the lactate:pyruvate and alanine:pyruvate ratios decreased 42% and 78%, respectively (P < 0.05) following gadoxetate administration. In kidneys, these ratios did not change significantly. Relaxivity of gadoxetate for [1-13C]alanine was 12.6 times higher than relaxivity of gadoxetate for [1-13C]pyruvate, explaining the greater selective relaxation effect on alanine.



The liver-specific gadolinium contrast-agent gadoxetate can selectively suppress normal hepatocyte contributions to hyperpolarized13C MRI signals. Magn Reson Med 77:2356-2363, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Michael A
MA
Ohliger
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Cornelius
C
von Morze
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Irene
I
Marco-Rius
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Jeremy
J
Gordon
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Peder E Z
0000-0003-4183-3634
PEZ
Larson
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Robert
R
Bok
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Hsin-Yu
HY
Chen
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
John
J
Kurhanewicz
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
Daniel
D
Vigneron
D000818:Animals; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D004338:Drug Combinations; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002247:Carbon Isotopes; D004338:Drug Combinations; C073590:gadolinium ethoxybenzyl DTPA; C000615229:Carbon-13; D019786:Gadolinium DTPA
gadoxetate; hyperpolarized carbon; liver; metabolism; pyruvate