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

Abstract

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). 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). 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). Extracellular volume measured by EQ-CT imaging can accurately predict the potential DILI through the quantification of ECV changes.