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<p>Metabolic dysfunction and hepatocellular injury coexist in liver disease but remain difficult to disentangle non-invasively. Hyperpolarized magnetic resonance imaging (HP MRI) enables in vivo metabolic interrogation but has primarily been applied to rapid exchange pathways. Here we evaluate whether complementary hyperpolarized molecular probes provide pathway-specific information on hepatic injury and methyl-donor metabolism in a rat model of steatohepatitis induced by a methionine- and choline-deficient diet. Hyperpolarized [1,4-<sup>13</sup>C<sub>2</sub>]fumarate MRI detected robust conversion to [1,4-<sup>13</sup>C<sub>2</sub>]malate in diseased livers, reflecting injury-associated fumarate hydratase accessibility following loss of membrane integrity. In the same animals, hyperpolarized <sup>15</sup>N,d<sub>9</sub>-betaine enabled detection of downstream <sup>15</sup>N,d<sub>6</sub>-dimethylglycine as a readout of hepatic one-carbon metabolism over a multi-minute timescale. While malate signal increased markedly in steatohepatitis, dimethylglycine formation was reduced despite comparable parent betaine signal, indicating impaired metabolic engagement rather than altered substrate delivery. These hyperpolarized contrast mechanisms provide complementary metabolic readouts of hepatic injury and methyl-donor metabolism in vivo, extending hyperpolarized MRI toward probing endogenous metabolic processes on extended timescales.</p>

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Complementary hyperpolarized 13C and 15N MRI reveal divergent signatures of hepatic injury and methyl-donor metabolism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月17日

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  • Ingeborg S. Skre,
  • Magnus Karlsson,
  • Juan D. Sánchez-Heredia,
  • Vebjørn S. Skre,
  • Peter A. Rasmussen,
  • Mathilde H. Lerche

摘要

Metabolic dysfunction and hepatocellular injury coexist in liver disease but remain difficult to disentangle non-invasively. Hyperpolarized magnetic resonance imaging (HP MRI) enables in vivo metabolic interrogation but has primarily been applied to rapid exchange pathways. Here we evaluate whether complementary hyperpolarized molecular probes provide pathway-specific information on hepatic injury and methyl-donor metabolism in a rat model of steatohepatitis induced by a methionine- and choline-deficient diet. Hyperpolarized [1,4-13C2]fumarate MRI detected robust conversion to [1,4-13C2]malate in diseased livers, reflecting injury-associated fumarate hydratase accessibility following loss of membrane integrity. In the same animals, hyperpolarized 15N,d9-betaine enabled detection of downstream 15N,d6-dimethylglycine as a readout of hepatic one-carbon metabolism over a multi-minute timescale. While malate signal increased markedly in steatohepatitis, dimethylglycine formation was reduced despite comparable parent betaine signal, indicating impaired metabolic engagement rather than altered substrate delivery. These hyperpolarized contrast mechanisms provide complementary metabolic readouts of hepatic injury and methyl-donor metabolism in vivo, extending hyperpolarized MRI toward probing endogenous metabolic processes on extended timescales.