Quantitative Assessment of Extracellular Volume in Doxorubicin-Induced Liver Injury in Beagle Models by Equilibrium Computed Tomography

PURPOSE: The purpose of this study was to determine whether liver extracellular volume (ECV) measured using equilibrium computed tomography (EQ-CT) can be used to quantitatively assess doxorubicin-induced liver injury (DILI). METHODS: The ethical approval was obtained from the Institutional Animal Care and Use Committee regulations. Thirteen dogs administered with doxorubicin for 0 to 24 weeks were imaged by contrast-enhanced EQ-CT. The dogs were divided into 3 groups: the baseline (13 dogs), 16-week (10 dogs), and 24-week (7 dogs) groups. Pathological analysis of the liver was performed using hematoxylin-eosin and Masson staining. Liver ECV uptake was calculated for each group and correlated with the histopathological and serological findings of hepatic fibrosis (hyaluronic acid and procollagen type III). RESULTS: In the baseline group, the median ECVs of the right and left liver lobes were 21.78% (interquartile range [IQR], 16.78%-26.68%) and 20.91% (IQR, 16.39%-24.07%), respectively. In the 16- and 24-week groups, the median ECVs of these 2 liver lobes were 28.18% (IQR, 20.56%-34.61%) and 25.96% (IQR, 14.07%-41.38%) and 29.71% (IQR, 27.19%-35.25%) and 29.22% (IQR, 22.62%-38.67%), respectively. There were no significant differences in ECV between the left and right lobes in the 3 groups (P < 0.05). Both the 16- and 24-week groups showed significantly higher ECV than did the primary group (P = 0.001-0.0006). However, there were no significant differences in ECV between the 16-week group and 24-week group (P = 0.412). There was a positive correlation between the serum index and edema due to the inflammation and necrosis associated with DILI (R = 0.6534, R = 0.7129). CONCLUSIONS: Extracellular volume measured by EQ-CT imaging can accurately predict the potential DILI through the quantification of ECV changes.