Gd-EOB-DTPA-enhanced MRI in the diagnosis of intrahepatic cholestasis in mice: an experimental study.

BACKGROUND

The diagnosis of intrahepatic cholestasis remains challenging due to a lack of reliable noninvasive biomarkers. This study aimed to define the diagnostic utility of semi-quantitative parameters from Gd-EOB-DTPA-enhanced MRI for assessing pathological severity in a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced intrahepatic cholestasis.

METHODS

Thirty female Kunming mice were divided into control (n = 5) and DDC-fed (n = 20) groups. Multi-timepoint (0-60 min post-injection) Gd-EOB-DTPA-enhanced MRI at 3.0T was performed to derive kinetic parameters-maximum relative enhancement (REmax), time-to-peak (TTP), and maximum slope (Slopemax)-from liver parenchyma and gallbladder. Histopathological scoring of key features (bile duct proliferation, cholestasis, hepatocyte degeneration, periductular fibrosis, porphyrin emboli) and serum biochemistry served as reference standards. Correlations and diagnostic performance were analyzed statistically.

RESULTS

DDC feeding induced progressive cholestatic injury, evident on histology from week 2 onward. MRI revealed distinct kinetic impairments: attenuated hepatic REmax (strong inverse correlations with bile duct proliferation [rs = -0.661, P = 0.0003] and cholestasis [rs = -0.546, P = 0.005]) and suppressed gallbladder positive Slopemax (inversely correlated with cholestasis severity [rs = -0.663, P = 0.0003]). Gallbladder positive Slopemax demonstrated exceptional diagnostic accuracy (AUC = 0.950), outperforming hepatic parameters. Serum biomarkers (AST, ALT) were elevated but did not correlate with MRI kinetics.

CONCLUSIONS

Gd-EOB-DTPA-enhanced MRI quantitatively captures functional impairment in mice intrahepatic cholestasis. Gallbladder excretion kinetics (Slopemax) and hepatic uptake (REmax) serve as sensitive, non-invasive biomarkers strongly correlated with histopathological severity, offering a promising approach for functional assessment that complements conventional serology and morphology.