Hyperpolarized MRI Detects Increased [1‐ ¹³ C]Pyruvate Metabolism in Early Liver Regeneration

ABSTRACT

Surgical resection remains the primary curative approach for malignant liver tumors and liver regeneration is essential for patient recovery following major hepatic resection. While its molecular and cellular mechanisms have been extensively studied, the in vivo metabolic dynamics underlying early regeneration remain incompletely characterized. Hyperpolarized [1‐ ¹³ C]pyruvate MRI (HP‐MRI) offers a unique, noninvasive method to assess real‐time metabolic fluxes in regenerating liver tissue. Twelve male Wistar rats were randomized to either 70% partial hepatectomy (PH; n  = 6) or nonsurgical controls ( n  = 6). On postoperative day 1, all animals underwent HP‐MRI and multiparametric proton MRI. Metabolic fluxes were quantified using area‐under‐the‐curve ratios for lactate‐to‐pyruvate (L/P), alanine‐to‐pyruvate (A/P), and lactate‐to‐alanine (L/A). The PH group showed significantly higher L/P (0.267 [95% CI: 0.225–0.310] vs. 0.168 [95% CI: 0.135–0.200]; p  < 0.001) and A/P (0.236 [95% CI: 0.153–0.319] vs. 0.150 [95% CI: 0.128–0.172]; p  = 0.028) ratios compared to controls, indicating increased exchange of pyruvate to lactate and alanine. L/A ratios remained unchanged. These findings were supported by elevated biochemical markers of hepatic injury and changes in quantitative MRI parameters, including reduced ADC and IVIM flow fraction. HP‐MRI revealed increased glycolytic and transaminase activity during early liver regeneration, consistent with the metabolic demands of hepatocyte proliferation. These results demonstrate the feasibility of HP‐MRI for noninvasive metabolic assessment of liver regeneration in vivo and additionally provide insights into early regenerative metabolism. This suggests HP‐MRI as a promising tool for assessing postoperative recovery in patients undergoing major hepatectomy.