Purpose: To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis.
Materials and methods: All procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions.
Results: Ishak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively).
Conclusion: Contrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model.
Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.
RSNA, 2012