Distinguishing metabolic signals of liver tumors from surrounding liver cells using hyperpolarized 13 C MRI and gadoxetate

Magn Reson Med. 2024 May;91(5):2114-2125. doi: 10.1002/mrm.29918. Epub 2024 Jan 25.

Abstract

Purpose: To use the hepatocyte-specific gadolinium-based contrast agent gadoxetate combined with hyperpolarized (HP) [1-13 C]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 13 C 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 [1-13 C] 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 13 C MRI metabolic signals (through T1 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 13 C MRI.

Keywords: CC531; Eovist; carbon-13; colon cancer; gadolinium; gadoxetate; hyperpolarized MRI; liver.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Contrast Media* / pharmacology
  • Gadolinium / pharmacology
  • Gadolinium DTPA
  • Hepatocytes / metabolism
  • Lactates / metabolism
  • Liver / metabolism
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / metabolism
  • Magnetic Resonance Imaging / methods
  • Pyruvates / metabolism
  • Rats

Substances

  • Contrast Media
  • Gadolinium
  • gadolinium ethoxybenzyl DTPA
  • Gadolinium DTPA
  • Pyruvates
  • Lactates