Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.
OBJECTIVE
To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model.


METHODS
Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia.


RESULTS
Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively).


CONCLUSIONS
CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Lin
L
Zhai
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Lan-Yan
LY
Qiu
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Yuan
Y
Zu
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Yan
Y
Yan
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Xiao-Zhuan
XZ
Ren
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Jun-Feng
JF
Zhao
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Yu-Jiang
YJ
Liu
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Ji-Bin
JB
Liu
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Lin-Xue Qian, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Lin-Xue
LX
Qian
D000818:Animals; D019540:Area Under Curve; D001706:Biopsy; D001783:Blood Flow Velocity; D001795:Blood Pressure Determination / Q000379:methods*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D003287:Contrast Media; D004285:Dogs; D005240:Feasibility Studies; D005260:Female; D006499:Hepatic Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006975:Hypertension, Portal / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008099:Liver / Q000473:pathology; D008102:Liver Circulation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D010743:Phospholipids; D017082:Portal Pressure; D011169:Portal Vein / Q000000981:diagnostic imaging* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D012039:Regional Blood Flow; D013459:Sulfur Hexafluoride; D013997:Time Factors; D014463:Ultrasonography
D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D002251:Carbon Tetrachloride; D013459:Sulfur Hexafluoride
Animal model; Contrast-enhanced ultrasound; Liver fibrosis; Noninvasive technique; Portal venous pressure