Distinguishing metabolic signals of liver tumors from surrounding liver cells using hyperpolarized 13C MRI and gadoxetate
Shubhangi Agarwal, Jeremy Gordon, Robert A. Bok, Cornelius von Morze, Daniel B. Vigneron, John Kurhanewicz, Michael A. Ohliger
Abstract
Purpose
To use the hepatocyte-specific gadolinium-based contrast agent gadoxetate combined with hyperpolarized (HP) [1-13C]pyruvate MRI to selectively suppress metabolic signals from normal hepatocytes while preserving the signals arising from tumors.
Methods
Simulations were performed to determine the expected changes in HP 13C MR signal in liver and tumor under the influence of gadoxetate. CC531 colon cancer cells were implanted into the livers of five Wag/Rij rats. Liver and tumor metabolism were imaged at 3 T using HP [1-13C] pyruvate chemical shift imaging before and 15 min after injection of gadoxetate. Area under the curve for pyruvate and lactate were measured from voxels containing at least 75% of normal-appearing liver or tumor.
Results
Numerical simulations predicted a 36% decrease in lactate-to-pyruvate (L/P) ratio in liver and 16% decrease in tumor. In vivo, baseline L/P ratio was 0.44 ± 0.25 in tumors versus 0.21 ± 0.08 in liver (p = 0.09). Following administration of gadoxetate, mean L/P ratio decreased by an average of 0.11 ± 0.06 (p < 0.01) in normal-appearing liver. In tumors, mean L/P ratio post-gadoxetate did not show a statistically significant change from baseline. Compared to baseline levels, the relative decrease in L/P ratio was significantly greater in liver than in tumors (−0.52 ± 0.16 vs. −0.19 ± 0.25, p < 0.05).
Conclusions
The intracellular hepatobiliary contrast agent showed a greater effect suppressing HP 13C MRI metabolic signals (through T 1 shortening) in normal-appearing liver when compared to tumors. The combined use of HP MRI with selective gadolinium contrast agents may allow more selective imaging in HP 13C MRI.