MRI Measures of Murine Liver Fibrosis

Background An imaging method that allows quantitative fibrosis estimates is needed to facilitate the diagnosis of chronic liver disease. Amide proton transfer (APT) and tissue sodium concentration (TSC) estimates could meet this need. Hypothesis APT and TSC estimates correlate with fibrosis in a mouse model of chronic liver disease. Study Type Prospective. Phantoms/Animal Model Male C57Bl/6 mice given CCl4 or vehicle (N = 8 each) twice weekly for 16 weeks. Field Strength/Sequence Liver T-1 (Look-Locker gradient recalled echo [GRE] sequence), T-2 (multiecho spin echo sequence), T-1rho (fast spin echo sequence with 500 Hz spin locking pulse), and APT (GRE sequence with off-resonance pulses) data were acquired at 7 T at 12 and 16 weeks. Liver sodium data (multiple echo GRE sequence) were acquired at 12 weeks at 9.4 T. Assessment Liver proton T-1, T-2, T-1rho, APT, sodium T-2*, and TSC were calculated. Histological measures included Sirius Red, hematoxylin and eosin, liver hydroxyproline content, and serum alanine transaminase (ALT). Statistical Tests Welch's two-sided t-test was used to test for differences between control and CCl4-treated groups for serum ALT, hydroxyproline, Sirius Red staining, T-1, T-2, T-1rho, APT, TSC, and sodium T-2*. Pearson's correlations between liver T-1, APT, TSC, or sodium T-2* with Sirius Red staining and hydroxyproline levels were calculated. Results APT was significantly different (P < 0.05) between groups in the left liver lobe at 16 weeks (CCl4: 8.0% +/- 1.2%, controls: 6.2% +/- 1.0%), as were average liver TSC at 12 weeks (CCl4: 38 mM +/- 5 mM, controls: 27 mM +/- 2 mM), and average sodium liver T-2* at 12 weeks (CCl4: 10 msec +/- 1.0 msec, controls: 12 msec +/- 1.9 msec). APT, TSC, and sodium T-2* correlated significantly (P < 0.05) with Sirius Red staining and hydroxyproline levels. Data Conclusion Liver TSC and APT significantly correlated with histopathologic markers of fibrosis in this mouse model. Evidence Level 1 Technical Efficacy Stage 3.

Automated summary

The study demonstrated that Amide Proton Transfer (APT) and Tissue Sodium Concentration (TSC) correlate with fibrosis in a mouse model of chronic liver disease, suggesting potential clinical applications.