Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2015; 21(15): 4509-4516
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4509
Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis
Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Ji-Bin Liu, Lin-Xue Qian
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 Liu, Ultrasound/Radiology, Thomas Jefferson University, Philadelphia, PA 19107, United States
Author contributions: Qian LX and Zhai L designed the study; Zhai L, Qiu LY, Zu Y, Yan Y, Ren XZ, Zhao JF, Liu YJ and Qian LX performed the experiments; Zhai L, Qiu LY, Zu Y, Yan Y and Ren XZ participated in the treatment of animals; Qian LX and Zhai L analyzed the data; Zhai L and Liu JB wrote the paper.
Ethics approval: The study was reviewed and approved by the Beijing Friendship Hospital Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Beijing Friendship Hospital, Capital Medical University (IACUC protocol number: 12-5001).
Conflict-of-interest: The authors declare no conflicting interest.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lin-Xue Qian, MD, Department of Ultrasonography, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Beijing 100050, China. qianlinxue2002@163.com
Telephone: +86-10-63138576 Fax: +86-10-63138217
Received: November 14, 2014
Peer-review started: November 17, 2014
First decision: December 11, 2014
Revised: December 31, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: April 21, 2015
Processing time: 156 Days and 23.4 Hours
Abstract

AIM: 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).

CONCLUSION: CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

Keywords: Animal model; Contrast-enhanced ultrasound; Liver fibrosis; Noninvasive technique; Portal venous pressure

Core tip: The measurement of portal pressure plays an important role in the evaluation of liver disease progression. Contrast-enhanced ultrasound techniques can provide hemodynamic parameters of blood circulation and tissue perfusion. The introduction of the area under the time-intensity curve and intensity at portal/arterial phase parameters has obvious advantages over absolute values, such as peak intensity, as the approach reduces other sources of interference. These parameters were negatively correlated with free portal pressure, supporting the use of contrast-enhanced ultrasound as a method to non-invasively estimate portal pressure.