Proof-of-Concept Study of Hyperpolarized [1-¹³C]Pyruvate MRI in Participants with Hepatocellular Carcinoma

Purpose To assess the feasibility of hyperpolarized [1-¹³C]pyruvate MRI (HP-MRI) as an adjunct to standard CT/MRI-based Liver Imaging Reporting and Data System (LI-RADS) categorization for noninvasive metabolic characterization of hepatocellular carcinoma (HCC). Materials and Methods This prospective, exploratory, single-center study included participants with liver lesions and control participants who underwent HP-MRI between June 2023 and June 2025. Lesions identified on CT and/or MRI scans were categorized according to LI-RADS. HP-MRI metabolic readout included ratios from dynamic ¹³C imaging, such as the lactate-to-pyruvate (L/P) ratio, alanine-to-pyruvate (A/P) ratio, alanine-to-lactate (A/L) ratio, and corresponding tumor-to-background ratios (TBRs). Established HCCs were compared with indeterminate lesions that subsequently progressed to HCC using unpaired t tests and Hedges g. Results Fourteen participants were included (median age, 64 years; IQR, 53-70 years]; 14 [100%] male): 10 participants with lesions on CT/MRI scans and four control participants. A/P and A/L ratios were lower in indeterminate lesions that progressed (n = 4) than established HCCs (n = 5), both in absolute measures and indexed to TBRs (P < .05), whereas there was no evidence of differences in the L/P ratio. In contrast, L/P TBR was higher in indeterminate lesions that progressed than in established HCCs (P = .03). Alanine-indexed TBRs showed large effect sizes, with Hedges g ranging from 2.01 (95% CI: 0.33, 3.70) to 3.02 (95% CI: 0.97, 5.08). One LI-RADS category 3 (LR-3) lesion under surveillance showed no early progression, and progression could not be confirmed for an LR-4 lesion. Conclusion Adjunctive HP-MRI provided complementary lesion-level metabolic information beyond standard CT and/or MRI, and a reduced A/L ratio emerged as a candidate marker of malignant progression. Keywords: Liver, Oncology, Cirrhosis, Hepatocellular Carcinoma Supplemental material is available for this article. Clinical Trials Information System hosted by the European Medicines Agency (EU-CTIS 2024-512490-27-00) © RSNA, 2026.