Medical Engineering and Physics 39 (2017) 66–72
Contents lists available at ScienceDirect
Medical Engineering and Physics
journal homepage: www.elsevier.com/locate/medengphy
Model-dependent and model-independent approaches for evaluating
hepatic fibrosis in rat liver using shearwave dispersion ultrasound
vibrometry
Haoming Lin
a
, Xinyu Zhang
a , b , c
, Yuanyuan Shen
a , b , c , ∗
, Yi Zheng
d
, Yanrong Guo
a
, Ying Zhu
a
,
Xianfen Diao
a , b , c
, Tianfu Wang
a , b , c
, Siping Chen
a , b , c
, Xin Chen
a , b , c , ∗
a
School of Biomedical Engineering, Shenzhen University, Shenzhen, China
b
National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Shenzhen, China
c
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Shenzhen, China
d
Department of Electrical and Computer Engineering, St. Cloud State University, St. Cloud, MN 56301, USA
a r t i c l e i n f o
Article history:
Received 18 December 2015
Revised 18 October 2016
Accepted 23 October 2016
Keywords:
Liver fibrosis
Shear wave velocity
Dispersion
Elastography
Model-dependent and model-independent
approaches
a b s t r a c t
This study assesses gradations of hepatic fibrosis in rat livers using both model-dependent and model-
independent approaches. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl
4
); 6 rats
served as the controls. Shear wave velocity as a function of frequency, referred to as velocity dispersion,
was measured in vitro by an ultrasound elastography method called shearwave dispersion ultrasound vi-
brometry (SDUV). For the model-dependent approach, the velocity dispersion data were fit to the Voigt
model to solve the viscoelastic modulus. For the model-independent approach, the pattern of the ve-
locity dispersion data was analyzed by linear regression to extract the slope and intercept features. The
parameters obtained by both approaches were evaluated separately using a receiver operating character-
istic (ROC) curve analysis. The results show that, of all the parameters for differentiating between grade
F0–F1 and grade F2–F4 fibrosis, the intercept had the greatest value for the area under the ROC curve.
This finding suggests that the model-independent approach may provide an alternative method to the
model-dependent approach for staging liver fibrosis.
©2016 IPEM. Published by Elsevier Ltd. All rights reserved.
1. Introduction
Liver fibrosis results from chronic damage to the liver in
conjunction with excessive accumulation of extracellular matrix
protein. The main causes of liver fibrosis include many types of
chronic liver diseases, such as hepatitis virus infection and alco-
holic and non-alcoholic fatty liver disease [1] . The gold standard
for assessing the degree of fibrosis is biopsy. However, liver biopsy
is an invasive procedure with potential complications such as
bleeding and pain [2] . In addition, sampling errors may occur
because an extremely small portion of the liver is sampled and
liver fibrosis is heterogeneously distributed [3] . Therefore, reliable,
simple and non-invasive methods for assessing liver fibrosis are
needed [4,5] .
Recently, a number of ultrasound-based elastography tech-
niques, including strain elastography [6] , transient elastography
(TE) [7,8] , acoustic radiation force impulse (ARFI) imaging [9] ,
∗
Corresponding authors at: School of Biomedical Engineering, Shenzhen Univer-
sity, Shenzhen, China.
E-mail addresses: yyshen@szu.edu.cn (Y. Shen), chenxin@szu.edu.cn (X. Chen).
supersonic shear imaging (SSI) [10] , and shearwave dispersion
ultrasound vibrometry (SDUV) [11] , have been applied to non-
invasively measure the biomechanical properties of the liver for
evaluating fibrosis. These techniques usually apply an external
force or acoustic radiation force to induce a deformation or dis-
placement in the soft tissue and detect the dynamic response
of the soft tissue to these forces, which relates qualitatively or
quantitatively to the mechanical properties of the soft tissue.
Some recent review papers have summarized various current
commercially available elastographic techniques and discussed
their characteristics, limitations and suitability for specific clinical
applications [12–14] . Of these methods, TE and ARFI have been
widely used in clinical practice for the evaluation of liver fibrosis
and have been validated in large cohorts of patients with chronic
hepatitis B and C, and non-alcoholic fatty liver disease (NAFLD)
[15–22] . For the patients with viral hepatitis, the detection of
significant fibrosis (METAVIR score ≥ F2) is clinically important
because it indicates that patients should receive antiviral treat-
ment [23] . It is regarded that both TE and ARFI can provide
reliable measurements of liver stiffness for assessing significant
fibrosis and can help to reduce the use of liver biopsies [24] .
http://dx.doi.org/10.1016/j.medengphy.2016.10.007
1350-4533/© 2016 IPEM. Published by Elsevier Ltd. All rights reserved.