MRI Measures of Murine Liver Fibrosis.

ABSTRACT

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 T1 (Look-Locker gradient recalled echo [GRE] sequence), T2 (multiecho spin echo sequence), T1rho (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 T1 , T2 , T1rho , APT, sodium T2 *, 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, T1 , T2 , T1rho , APT, TSC, and sodium T2 *. Pearson's correlations between liver T1 , APT, TSC, or sodium T2 * 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 T2 * at 12 weeks (CCl4 10 msec ± 1.0 msec, controls 12 msec ± 1.9 msec). APT, TSC, and sodium T2 * 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.