Non-invasive quantification of hepatic fibrosis in the CCl4 mouse model by magnetic resonance relaxometry (MRR): first results

Aims: To date research involving mouse models of liver fibrosis is hampered by the need of obtaining liver specimens to quantify liver injury. Hence development of non-invasive methods is critical to monitor potential therapies for hepatic fibrosis and to reduce the number of animals included in experiments. Our aim was to establish a protocol for non-invasive quantification of liver fibrosis in mice using magnetic resonance relaxometry (MRR). Methods: We studied BALB/cJ mice (n=10) after induction of liver fibrosis with CCl₄ (1.4mg/kg/week i.p. for 6 weeks) and control animals (n=11). To determine hepatic injury and fibrosis, serum activities of liver enzymes (ALT, AST) and hepatic collagen contents (via hydroxyproline, Hyp) were quantified. MRR was performed on a horizontal bore 9.4 Tesla animal scanner (Bruker Biospec 9.4/200) with a circular polarized receive/transmit coil. The relaxation times T1, T2 and T2* were acquired with turbo spin echo and multiple gradient echo techniques. Results: Compared to untreated mice, animals challenged with CCl₄ demonstrate significantly (p<0.001) increased hepatic collagen contents and transaminase activities. CCl₄-challenged mice display a significant (p<0.01) reduction of the T2- (18.5±0.5 vs. 20.2±0.6 ms) and T2* (8.0±0.2 vs. 9.3±0.2 ms) relaxation times as compared to controls. Furthermore, T2* correlates significantly (p<0.05) with raised Hyp levels in CCl₄-treated animals (454.5±26.1 vs. 208.0±46.7 μg/g liver). On the other hand, the T1 relaxation times do not differ between CCl₄-treated and control animals. Conclusions: The present MRR protocol demonstrates the feasibility of MRR as non-invasive method to discriminate between fibrotic and non-fibrotic liver tissue in small animals. Additional studies are currently being performed to develop algorithms allowing differentiation of fibrosis stages and assessment of fibrosis resolution by MRR.

MRT - liver fibrosis - magnetic resonance relaxometry