Quantitative Functional Evaluation of Liver Fibrosis in Mice with Dynamic Contrast-enhanced Photoacoustic Imaging

Abstract

Background Dynamic contrast-enhanced (DCE) photoacoustic (PA) imaging (PAI) is a novel noninvasive imaging modality that uses the differences in optical absorption of oxyhemoglobin and deoxyhemoglobin and may be performed in a dynamic fashion to image the indocyanine green (ICG) pharmacokinetics in the liver. Purpose To determine whether DCE PAI parameters (maximum peak time [T_max] and half-life [T_1/2]) derived from the PA liver function curve correlate with fibrosis determined using histopathologic analysis. Materials and Methods Between June 2020 and October 2020, 28 male mice aged 8 weeks were intraperitoneally injected with carbon tetrachloride solution every 2 days to establish a liver fibrosis model. At the 1st, 4th, and 8th week of modeling, the changes in liver structure were monitored dynamically by using a PA technique. The T_max and T_1/2 of ICG were calculated at different pathologic stages and within a control group. Corresponding liver histopathologic results and blood biochemical data were obtained. Spearman rank correlation was used to evaluate the relationship between the DCE PAI results and histologic scores. Results The PA liver function curve showed that the T_max and T_1/2 varied among groups (mean T_max: control group, 9 seconds ± 1.8 [standard deviation]; 1 week, 51 seconds ± 4.4; 4 weeks, 73 seconds ± 5.3; 8 weeks, 104 seconds ± 6.6; P < .001) (mean T_1/2: control group, 28 seconds ± 6.5; 1 week, 201 seconds ± 12.4; 4 weeks, 285 seconds ± 11; 8 weeks, 318 seconds ± 30.5; P < .001). There was a positive correlation between the dynamic parameters (T_max and T_1/2) and the histopathologic scores; the Spearman ρ ratios for the Sirius red and α-smooth muscle actin (αSMA)-positive areas versus the T_max were 0.93 and 0.94 (P < .001 for both), and the Spearman ρ ratios for the Sirius red and αSMA-positive areas versus T_1/2 were 0.87 and 0.89 (P < .001 for both). Conclusion Dynamic contrast-enhanced photoacoustic imaging demonstrated a higher maximum peak time and half-life in mice with induced fibrosis compared with control mice without fibrosis, and these values correlated with histologic measures of fibrosis. © RSNA, 2021 Online supplemental material is available for this article.