Hyperpolarized γ-Glutamyl-[1-¹³C]Glycine MRI Detects Liver Injury Non-Invasively

To evaluate hyperpolarized (HP) γ-glutamyl-[1-¹³C]glycine ([¹³C]GG) MRI as a non-invasive method for assessing liver injury through imaging of hepatic enzymatic activity.

In this prospective preclinical imaging study, five mice underwent HP ¹³C MRI at baseline and 48 h after induction of acute liver injury with carbon tetrachloride (CCl₄). Dynamic slice-selective HP ¹³C spectra through the liver were acquired at 3 T. Signals from [¹³C]GG and its cleavage product [1-¹³C]glycine (catalyzed by γ-glutamyl-transferase or GGT) were quantified. Glycine-to-GG area-under-the-curve (AUC) ratios were calculated. Paired comparisons were analyzed using a two-tailed t-test. Liver histopathology was analyzed after imaging.

At baseline, HP [¹³C]GG demonstrated detectable in vivo hepatic conversion to [1-¹³C]glycine. Following CCl₄-induced injury, glycine production decreased in all animals despite similar substrate delivery. On average, the glycine-to-GG ratio declined by 25% (p = 0.024). Histology confirmed centrilobular necrosis, steatosis, inflammation, and hepatocyte injury, with relative preservation of periportal structures. Ex vivo GGT activity measurements (normalized to tissue mass) were directionally consistent with the imaging findings.

HP [¹³C]GG MRI detects alterations in hepatic extracellular enzymatic activity following acute injury. The observed reduction in product formation likely reflects changes in functional accessibility of enzyme activity due to tissue injury, highlighting the potential of HP MRI for non-invasive assessment of liver function.