Detection of Steatohepatitis in a Rat Model by Using Spectroscopic Shear-Wave US Elastography.

Abstract

Purpose To compare low- versus high-frequency ultrasonographic (US) elastography for detection of steatohepatitis in rats by using histopathologic findings as the reference standard. Materials and Methods Between March and September 2014, after receiving approval from the institutional animal care committee, 60 male Sprague-Dawley rats were fed either a standard chow for 4 weeks or a methionine- and choline-deficient diet for 1, 4, 8, or 12 weeks to induce a continuum of steatohepatitis severity. Liver shear stiffness was assessed in vivo by using US elastography at low (40-130-Hz) and high (130-220-Hz) frequencies. Histologic features (steatosis, inflammation, and fibrosis) and modified nonalcoholic steatohepatitis categories were used as reference standards. Definite steatohepatitis was divided into steatohepatitis with fibrosis stage 1 or lower and stage 2 and higher. Analyses included the Kendall τ correlation, multivariable linear regression analyses, Kruskal-Wallis rank sum test, and post hoc Dunn test with Holm correction. Results Correlations between liver shear stiffness and histologic features were higher at high frequencies than at low frequencies (low frequency: 0.08, 0.24, and 0.20 for steatosis, inflammation, and fibrosis, respectively; high frequency: 0.11, 0.35, and 0.50, respectively). The absolute value of multivariable regression coefficients was higher at high frequencies for the presence of steatosis, inflammation grade, and fibrosis stage (low frequency: -0.475, 0.157, and 0.209, respectively; high frequency: -0.893, 0.357, and 0.447, respectively). The model fit was better at high frequencies (adjusted R2 = 0.57) than at low frequencies (adjusted R2 = 0.21). There was a significant difference between steatohepatitis categories at both low and high frequencies (P = .022 and P < .001, respectively). Conclusion Liver shear stiffness measured with US elastography provided better distinction of steatohepatitis categories at high frequencies than at low frequencies. Further, liver shear stiffness decreased with steatosis and increased with inflammation and fibrosis at both low and high frequencies. © RSNA, 2016 Online supplemental material is available for this article.