Metabolic Changes in Different Stages of Liver Fibrosis: In vivo Hyperpolarized 13C MR Spectroscopy and Metabolic Imaging.

Abstract

The objective was to assess metabolic changes in different stages of liver fibrosis using hyperpolarized C-13 magnetic resonance spectroscopy (MRS) and metabolic imaging. Mild and severe liver fibrosis were induced in C3H/HeN mice (n = 14) by injecting thioacetamide (TAA). Other C3H/HeN mice (n = 7) were injected with phosphate buffer saline (PBS) (7.4 pH) as normal controls. Hyperpolarized C-13 MRS was performed on the livers of the mice, which was accompanied by intravoxel incoherent motion (IVIM) diffusion-weighted imaging with 12 b values. The differential metabolite ratios, apparent diffusion coefficient values, and IVIM parameters among the three groups were analyzed by a one-way analysis of variance test. The ratios of [1-13C]lactate/pyruvate, [1-13C]lactate/total carbon (tC), [1-13C]alanine/pyruvate, and [1-13C] alanine/tC were significantly higher in both the mild and severe fibrosis groups than in the normal control group (p < 0.05). While the [1-13C]lactate/pyruvate and [1-13C]lactate/tC ratios were not significantly different between mild and severe fibrosis groups, the ratios of [1-13C]alanine/pyruvate and [1-13C]alanine/tC were significantly higher in the severe fibrosis group than in the mild fibrosis group (p < 0.05). In addition, D* showed a significantly lower value in the severe fibrosis group than in the normal or mild fibrosis groups and negatively correlated with the levels of [1-13C] lactate and [1-13C]alanine. Our findings suggest that it might be possible to differentiate mild from severe liver fibrosis using the cellular metabolic changes with hyperpolarized C-13 MRS and metabolic imaging.