Humanized mouse models make it possible to study human specific pathogens in small animals. In this study we exploit a humanized mouse model with both human hepatocytes and human immune system to understand the inflammatory and fibrotic processes after hepatitis B virus infection. Diffusion weighted imaging (DWI) and arterial spin labelling (ASL) MRI were conducted to track the diffusivity and perfusion in the disease progression.The humanized mouse model with both human hepatocytes and human immune system was developed as reported elsewhere ¹. The mice were divided into two groups. One group was infected with Hepatitis B virus and the other group without infection was used as control. MRI was done on a 7 Tesla scanner (ClinScan, Bruker Biospin, Germany) with a mouse body volume coil for Tx/Rx. Mice were monitored over three months post infection. Liver anatomy was measured by a respiratory triggered T1w-Fast Spin Echo imaging (TR/TE=400/9 ms). Respiratory triggered DWI (TR/TE = 5000/24 ms; b = 0; 500; 1000 s mm 2) was obtained and then linearly registered to the anatomy and fit for mean diffusivity using FSL. T1 map was obtained using an inversion-recovery SE-EPI sequence with TR/TE=10000/18 ms and variable TI. FAIR ASL sequence with respiratory triggered SE-EPI (TR/TE = 4000 /18 ms; TI =100;350;750;1500;2500;3800 ms) was done, and fitted for quantitative perfusion ². Histo-pathological changes were studied.Infected mice developed liver lesions which showed hypo-intensity in T1-weighted images (figure 1A). The lesion areas had reduced mean diffusivity with the value of 0.007 mm²/s at the 3^rd month, compared to 0.01 mm²/s in normal liver (figure 1B,F). The lesion area also showed reduced perfusion, which was greatly attenuated from 500 mL/100g/min in normal liver to about 300 mL/100g/min in the infected liver as early as 1 month post infection (figure 1D,E). Histological studies confirmed the areas of liver with hypo-intensity to be associated with immune cell infiltration and with high collagen content as a result of fibrosis (figure 1G). Imaging pathological changes in liver infection is critical for evaluation of therapy towards viral hepatitis. We showed that an ensemble of imaging markers could indicate the progression of hepatitis B infection in a humanized mouse liver model. The reduced diffusivity may be related to collagen deposition ³. The highly reduced perfusion may be associated with splenomegaly with portal hypertension as result of viral infection ⁴. The hypo-intense lesion in T1-weighted MRI may be resulted from collagen deposition due to fibrosis. The multimodal approach would be useful biomarkers for translational study of therapeutic response in infectious liver diseases.