Ultrasensitive US microvessel imaging of hepatic microcirculation in the cirrhotic rat liver

Background: Liver microcirculation dysfunction plays a vital role in the occurrence and development of liver diseases, and thus, there is a clinical need for in vivo, noninvasive, and quantitative evaluation of liver microcirculation. Purpose: To evaluate the feasibility of ultrasensitive US microvessel imaging (UMI) in the visualization and quantification of hepatic microvessels in healthy and cirrhotic rats. Materials and Methods: In vivo studies were performed to image hepatic microvasculature by means of laparotomy in Sprague-Dawley rats (five cirrhotic and five control rats). In vivo conventional power Doppler US and ex vivo micro-CT were performed for comparison. UMI-based quantifications of perfusion, tortuosity, and integrity of microvessels were compared between the control and cirrhotic groups by using the Wilcoxon test. Spearman correlations between quantification parameters and pathologic fibrosis, perfusion function, and hepatic hypoxia were evaluated. Results: UMI helped detect minute vessels below the liver capsule, as compared with conventional power Doppler US and micro-CT. With use of UMI, lower perfusion indicated by vessel density (median, 22% [IQR, 20% 28%] vs 41% [IQR, 37% 46%]; P = .008) and fractional moving blood volume (FMBV) (median, 6.4% [IQR, 4.8% 8.6%] vs 13% [IQR, 12% 14%]; P = .008) and higher tortuosity indicated by the sum of angles metric (SOAM) (median, 3.0 [IQR, 2.9 3.0] vs 2.7 [IQR, 2.6 2.9]; P = .008) were demonstrated in the cirrhotic rat group compared with the control group. Vessel density (r = 0.85, P = .003), FMBV (r = 0.86, P = .002), and median SOAM (r = -0.83, P = .003) showed strong correlations with pathologically derived vessel density labeled with dextran. Vessel density (r = -0.81, P = .005) and median SOAM (r = 0.87, P = .001) also showed strong correlations with hepatic tissue hypoxia. Conclusion: Contrast-free ultrasensitive US microvessel imaging provided noninvasive in vivo imaging and quantification of hepatic microvessels in cirrhotic rat liver.