Noninvasive Evaluation of Liver Fibrosis Using Real-time Tissue Elastography and Transient Elastography (FibroScan)

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1 ORIGINAL RESEARCH Noninvasive Evaluation of Liver Fibrosis Using Real-time Tissue Elastography and Transient Elastography (FibroScan) Fankun Meng, MD, Ying Zheng, MD, Qi Zhang, MD, Xiaojie Mu, MD, Xiaoluan Xu, MD, Haiying Zhang, MD, Lei Ding, MD Received February 10, 2014, from the Department of Ultrasound, You an Hospital, Capital Medical University, Beijing, China (F.M., Y.Z., X.M., X.X., H.Z., L.D.); and Department of Ultrasound, Hitachi Medical Corporation, Beijing, China (Q.Z.). Revision requested March 7, Revised manuscript accepted for publication June 17, Drs Meng and Zheng contributed equally to this work. Address correspondence to Fankun Meng, MD, of Ying Zheng, MD, Department of Ultrasound, You an Hospital, Capital Medical University, 8 Youwai Xitoutiao St, Feng Tai District, Beijing, China. mengfankun818@126.com Abbreviations AUC, area under the curve; ROI, region of interest doi: /ultra Objectives The purpose of this study was to assess liver fibrosis with real-time tissue elastography and to compare the results with those of transient elastographic (FibroScan; Echosens, Paris, France) measurements by using liver biopsy as the reference standard. Methods Real-time tissue elastography and percutaneous liver biopsy were performed in 166 patients with chronic hepatitis B (estimation group). The relationship between the parameters obtained via real-time tissue elastography and the hepatic fibrosis stage was evaluated by a stepwise multiple linear regression, and the regression equation was used to calculate the liver fibrosis index. The diagnostic performance of the liver fibrosis index was validated and compared with FibroScan in 121 other patients with chronic hepatitis B (validation group). Results The liver fibrosis index was calculated as follows: liver fibrosis index = low-strain area ratio skewness mean kurtosis. The liver fibrosis index and liver stiffness measured by FibroScan were both significantly associated with the fibrosis stage in the validation group (r= and 0.664, respectively; both P<.001). The areas under the receiver operating characteristic curves for the liver fibrosis index and liver stiffness were and for predicting substantial fibrosis (scores F2), and for predicting severe fibrosis ( F3), and and for predicting cirrhosis (F4), respectively. Conclusions Real-time tissue elastography is an effective method for assessing liver fibrosis, with diagnostic performance similar to that of transient elastography. Key Words chronic hepatitis B; gastrointestinal ultrasound; FibroScan; liver fibrosis; real-time tissue elastography The prognosis of patients with chronic viral hepatitis is closely related to the progression of hepatic fibrosis. A precise assessment of the stage of hepatic fibrosis is important for surveillance and treatment decisions in patients with chronic hepatitis. 1 At present, liver biopsy is the reference standard for the diagnosis of liver fibrosis. 2 However, it is an invasive method, which is associated with physical and mental discomfort and is not suitable for patients who need to be examined repeatedly to monitor the progression of hepatic fibrosis. 3 In addition, the accuracy of liver biopsy is limited because of sampling errors. 4 Furthermore, there are considerable intraobserver and interobserver variabilities when analyzing the same biopsy sample. 5 Therefore, a few alternative noninvasive methods have been proposed for evaluation of the liver fibrosis stage, such as sonographic transient elastography (FibroScan; 2015 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2015; 34:

2 Echosens, Paris, France), 6 9 real-time tissue elastography, and laboratory tests (ie, aspartate aminotransferaseto-platelet ratio index, 18 FibroIndex, 19 Forns score, 20 Hepascore, 21 FibroTest, 22 and FibroMeter 23 ). FibroScan is based on sonographic measurement of the propagation velocity of an elastic shear wave: the faster the wave, the stiffer the medium. It measures liver stiffness, expressed in kilopascals. Liver stiffness measured by FibroScan has been reported to be well correlated with the histologically assessed liver fibrosis stage in patients with hepatitis B or C. 6 9 It can be used to accurately detect early hepatic fibrosis, 24 advanced fibrosis, 25 and cirrhosis. 8,9 Additionally, the recently developed XL probe has improved the feasibility of FibroScan in obese patients. 26,27 Nevertheless, there are technical limitations that may prevent accurate liver stiffness measurement in patients with ascites, severe hepatic atrophy, and narrow intercostal spaces. 28,29 Real-time tissue elastography is a recently developed ultrasound-based modality that enables visualization of tissue elasticity distribution juxtaposed with B-mode reference images even in patients with ascites and narrow intercostal spaces. 12,16 Extensive research on real-time tissue elastography has been focused on the evaluation of malignant tumors in the mammary gland, thyroid, prostate, and liver. Also, it is useful for diagnosis of liver fibrosis in diffuse liver diseases, especially hepatitis C The purpose of this study was to assess liver fibrosis with real-time tissue elastography in patients with chronic hepatitis B and to compare the results with those of FibroScan measurements by using liver biopsy as the reference standard. Materials and Methods Patients and Study Protocol This study was approved by the local Ethical Committee, and written informed consent was obtained from all participants. From August 2010 to June 2011, 348 consecutive inpatients with hepatitis B were referred to our institution for liver biopsy. Of these patients, 287 (139 men and 148 women; mean age ± SD, 37 ± 11 years; range, years) were included in the study. Study inclusion criteria were the presence of hepatitis B surface antigen with negative findings for serum anti hepatitis C virus antibodies. Exclusion criteria included ascites (because FibroScan cannot be applied to such cases), acute flares of chronic hepatitis, coinfection with other hepatitis viruses, and other liver diseases such as primary biliary cirrhosis and alcoholic liver disease. From August 2010 to January 2011, 166 of these patients (estimation group; 78 men and 88 women; mean age, 37 ± 9 years; range, years) were studied to develop the liver fibrosis index. Real-time tissue elastography and percutaneous liver biopsy were performed in the estimation group. From February 2011 to June 2011, the other 121 patients (validation group; 61 men and 60 women; mean age, 36 ± 13 years; range, years) were studied to validate the diagnostic performance of the liver fibrosis index obtained via real-time tissue elastography. The usefulness of the liver fibrosis index was compared with FibroScan and percutaneous liver biopsy. Fifteen healthy adult volunteers (5 men and 10 women; mean age, 29 ± 4 years; range, years) served as a control group. Inclusion criteria were normal liver enzyme levels, negative findings for anti hepatitis C virus antibodies, negative findings for hepatitis B surface antigen, no metabolic disorders, no history of relevant concomitant illness (heart, lung, or liver disease or neoplasia), and no history of long-term administration of any medication or excessive alcohol use. Real-time Tissue Elastography Liver elasticity was measured with real-time tissue elastography by a single experienced physician and with FibroScan by another experienced physician after overnight fasting on the same day. The physicians were blinded to the liver biopsy results and to each other s results. Real-time tissue elastography was performed with a HI VISION 900 ultrasound system (Hitachi Medical Corporation, Tokyo, Japan) using a 3 7-MHz linear array probe 24 to 48 hours before liver biopsy. All participants were examined in a supine position with the right arm tucked behind the head to facilitate probe access. The probe was placed on the intercostal space at the level of the right lobe of the liver by applying slight manual compression while the participants briefly held their breath. The deformation of the liver depended on the rhythmic beat of the heart and vessels. An identical area ( cm), 1 cm below the liver surface and free of large blood vessels, was set as the region of interest (ROI) for all participants. The frame of the ROI was chosen when the color-coded images on real-time tissue elastography were stable, and 11 parameters associated with tissue stiffness in the ROI given by the ultrasound device were read and recorded (Figure 1), including the mean and standard deviation of relative strain within the ROI, skewness and kurtosis on the strain histogram, low-strain (blue) area ratio within the ROI, complexity of the low-strain region, textural complexity, textural local homogeneity (inverse 404 J Ultrasound Med 2015; 34:

3 difference moment), textural homogeneity (angular second moment), contrast, and correlation. 10,12,14 Transient Elastography Transient elastography was performed with FibroScan before or after (in random order) real-time tissue elastography. The patient position and measurement sites for the FibroScan probe were the same as those for real-time tissue elastography. The measurements were performed until 10 valid results had been obtained. A median of 10 valid measurements was regarded as the liver stiffness for each participant, expressed in kilopascals. Measurements with an interquartile range-to-median ratio of 0.30 or higher, or an interquartile range-to-median ratio lower than 0.30 with a median of less than 7.1 kpa, were considered reliable. 30 Liver Histologic Analysis Sonographically guided percutaneous liver biopsy was performed using an 18-gauge needle with samples taken from the right lobe in each patient. The biopsy specimen was considered adequate if the number of portal tracts was at least 6 and the length of it was at least 1.2 cm. The biopsy specimen was fixed in formalin and embedded in paraffin. Four-micrometer-thick sections were stained with hematoxylin-eosin and Masson s trichrome. An experienced pathologist blinded to all patient characteristics analyzed all of the biopsy specimens. The liver fibrosis was staged on a scale of F0 to F4 according to the METAVIR scoring system: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis and few septa; F3, numerous septa without cirrhosis; and F4, cirrhosis. Figure 1. Representative real-time tissue elastogram from a patient with chronic viral hepatitis B. The intensity of blue indicates regions where fibrosis is more advanced. Statistical Analysis Continuous data are expressed as mean ± standard deviation unless otherwise indicated. Continuous variables were tested for normality of distribution with the Kolmogorov- Smirnov test. The 11 parameters obtained via real-time tissue elastography were introduced into a stepwise multiple linear regression to evaluate the relationship between the results from real-time tissue elastography (as independent variables) and the hepatic fibrosis stage (as a dependent variable) in the estimation group. The independent predictors of the hepatic fibrosis stage were selected, and the regression equation was used to calculate the liver fibrosis index. 10,12,14 The diagnostic performance of the liver fibrosis index obtained via real-time tissue elastography and liver stiffness obtained via FibroScan was assessed by receiver operating characteristic curves in the validation group. Optimal cutoff values for the liver fibrosis index and liver stiffness were chosen to maximize the sum of sensitivity and specificity. The DeLong test was used to compare the areas under the curves (AUCs) between the liver fibrosis index and liver stiffness. The correlations between the two sonographic methods and the histologic fibrosis stage were assessed by the Spearman correlation coefficient. Variables were compared among the histologic fibrosis stages by 1-way repeated measures analysis of variance followed by post hoc tests (Scheffé test for equal variances assumed and Dunnett C test for equal variances not assumed) if the analysis of variance resulted in significance when the data had a normal distribution or by Kruskal-Wallis 1-way analysis of variance on ranks when the normality test failed. All statistical analyses were performed with SPSS version 17.0 software (IBM Corporation, Armonk, NY) and MedCalc version software (MedCalc Software, Ostend, Belgium). P <.05 was considered statistically significant. Results General Characteristics Tables 1 3 depict the general characteristics of the estimation and validation groups. Real-time tissue elastography and FibroScan were both successfully performed. Hepatic fibrosis was also successfully assessed by liver biopsy from all patients. Liver Fibrosis Index by Real-time Tissue Elastography The values of 11 parameters obtained via real-time tissue elastography in the estimation and validation groups are shown in Tables 4 and 5. In the estimation group, the J Ultrasound Med 2015; 34:

4 low-strain area ratio, skewness, mean, and kurtosis were identified as the independent predictors of the liver fibrosis stage by multivariate linear regression analysis (liver fibrosis stage = low-strain area ratio skewness mean kurtosis; R 2 = 0.841; P <.001). This regression equation was used to calculate the liver fibrosis index in the validation group. Table 5 shows the liver fibrosis index for each fibrotic stage in the validation and control groups. There were significant differences between F1 and F2 and between F3 and F4 when compared between adjacent stages (both P <.05). The differences were significant when the liver fibrosis index was compared between nonadjacent fibrotic stages (all P <.05). The liver fibrosis index was significantly associated with the fibrosis stage in the validation group (r= 0.667; P <.001). As the liver fibrotic stage progressed, there tended to be a higher liver fibrosis index. The AUCs, which are measurements of the diagnostic accuracy of a test, were for the diagnosis of substantial fibrosis ( F2), for the diagnosis of severe fibrosis ( F3), and for the diagnosis of cirrhosis (F4; Figure 2). The optimal liver fibrosis index cutoff values, as well as the corresponding sensitivities and specificities, are shown in Table 6. Liver Stiffness by FibroScan Table 5 shows the liver stiffness measurements by FibroScan in the validation and control groups. There were significant differences between F1 and F2, between F2 and F3, and between F3 and F4 when liver stiffness was compared between adjacent fibrotic stages (all P <.05). Also, significant differences were observed between all nonadjacent fibrotic stages (all P <.05). For comparison of histologic liver fibrosis stages and liver stiffness, a high correlation of increasing liver stiffness with an increasing fibrosis stage was found (r = 0.664; P <.001). The AUCs for liver stiffness by FibroScan were for the diagnosis of substantial fibrosis ( F2), for the diagnosis of severe fibrosis ( F3), and for the diagnosis of cirrhosis (F4; Figure 2). The optimal cutoff Table 1. General Characteristics in the Estimation Group Characteristic F0 (n = 44) F1 (n = 38) F2 (n = 35) F3 (n = 33) F4 (n = 16) P Age, y 32 ± 7 34 ± 6 38 ± 8 a 40 ± 10 a,b 49 ± 9 a,b,c,d <.001 Male/female 17/27 20/18 16/19 15/18 10/6 <.001 BMI, kg/m 2 19 ± 4 20 ± 3 20 ± 4 21 ± 2 a 19 ± 5 d <.001 AST, IU/L ± ± a ± a,b ± a ± a,c <.001 ALT, IU/L ± ± ± a ± a,b ± c,d <.001 TBIL, μmol/l 9.15 ± ± ± 9.69 a ± 8.59 a ± 9.57 a,b <.001 DBIL, μmol/l 2.16 ± ± ± ± 2.11 a,b 7.01 ± 2.58 a,b <.001 PTA, % ± ± ± ± ± Platelets, 10 9 /L ± ± ± ± ± a,b,c <.001 Data are expressed as mean ± SD where applicable. ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; DBIL, direct bilirubin; PTA, prothrombin time activity; and TBIL, total bilirubin. a P <.05 versus F0; b P <.05 versus F1; c P <.05 versus F2; d P <.05 versus F3. Table 2. General Characteristics in the Validation and Control Groups Control Validation (n = 121) Characteristic (n = 15) F0 (n = 23) F1 (n = 42) F2 (n = 15) F3 (n = 12) F4 (n = 29) P Age, y 29 ± 4 28 ± 8 32 ± ± 9 39 ± ± 10 a,b,c,d <.001 Male/female 5/10 8/15 20/22 8/7 2/10 23/6 <.001 BMI, kg/m 2 20 ± 3 22 ± 2 a 21 ± 3 19 ± 4 b,c 20 ± 4 19 ± 4 b,c <.001 AST, IU/L ± ± ± a ± a,b,c ± a,d ± a,d <.001 ALT, IU/L ± ± a ± a ± a,b ± a,b ± a,d,e <.001 TBIL, μmol/l ± ± ± ± ± ± DBIL, μmol/l 2.60 ± ± ± ± 7.39 a,b 3.98 ± ± 4.62 a,b,e <.001 PTA, % ± ± ± ± ± ± Platelets, 10 9 /L ± ± ± ± ± ± a,b,c,d <.001 Data are expressed as mean ± SD where applicable. Abbreviations are as in Table 1. a P <.05 versus control; b P <.05 versus F0; c P <.05 versus F1; d P <.05 versus F2; e P < 0.05 versus F J Ultrasound Med 2015; 34:

5 values, as well as corresponding sensitivities and specificities, are shown in Table 6. The AUCs for real-time tissue elastography and FibroScan were statistically comparable for the diagnoses of substantial fibrosis ( F2; z = 1.245; P =.2132), severe fibrosis ( F3; z = 0.760; P =.4470), and cirrhosis (F4; z = 0.500; P =.6170). Therefore, real-time tissue elastography and FibroScan had a similar ability for discriminating hepatic fibrosis. Table 3. Comparison of General Characteristics Between the Estimation and Validation Groups Characteristic Estimation Validation P Age, y 37 ± 9 36 ± Male/female 78/88 61/ BMI, kg/m 2 20 ± 2 20 ± AST, IU/L ± ± ALT, IU/L ± ± TBIL, μmol/l ± ± DBIL, μmol/l 4.70 ± ± PTA, % ± ± Platelets, 10 9 /L ± ± Data are expressed as mean ± SD where applicable. Abbreviations are as in Table 1. Table 4. Results Obtained via Real-time Tissue Elastography in the Estimation Group Parameter F0 F1 F2 F3 F4 P Mean 117 ± ± ± 8 a,b 100 ± 12 a,b 93 ± 16 a,b,c <.001 SD 44 ± 5 48 ± 6 52 ± 7 a,b 59 ± 7 a,b,c 60 ± 5 a,b,c <.001 %Area 6.7 ± ± 5.0 a 19.4 ± 8.3 a,b 26.4 ± 12.0 a,b 33.1 ± 13.2 a,b,c <.001 COMP 17.5 ± ± 2.7 a 23.9 ± 4.4 a,b 25.6 ± 6.7 a,b 32.0 ± 10.7 a,b <.001 KURT 2.39 ± ± ± ± 0.23 a,b 2.42 ± SKEW ± ± ± ± a,b,c ± a,b,c <.001 CONT 145 ± ± ± 40 a,b 246 ± 48 a,b,c 242 ± 53 a,b,c <.001 ENT 3.77 ± ± 0.08 a 3.88 ± 0.06 a 3.88 ± 0.07 a 3.85 ± 0.13 <.001 IDM ± ± a ± a ± c ± <.001 ASM ± ± a ± ± b ± <.001 CORR ± ± ± ± ± Data are expressed as mean ± SD. %Area indicates low-strain area ratio within the ROI; ASM, angular second moment; COMP, complexity of the low-strain region; CONT, contrast; CORR, correlation; ENT, textural complexity; IDM, inverse difference moment; KURT, kurtosis; and SKEW, skewness. a P <.05 versus F0; b P <.05 versus F1; c P <.05 versus F2; d P <.05 versus F3. Table 5. Results Obtained via Real-time Tissue Elastography and FibroScan in the Validation and Control Groups Validation Parameter Control F0 F1 F2 F3 F4 P MEAN 116 ± ± ± ± 10 a 101 ± 9 a,b,c 92 ± 17 a,b,c,d,e <.001 SD 48 ± 5 51 ± ± 10 a 60 ± 8 a,b,c 65 ± 6 a,b,c 64 ± 8 a,b,c <.001 %Area 11.9 ± ± ±10.7 a 25.1 ± 10.3 a,b,c 30.6 ± 8.6 a,b,c 37.5 ± 14.4 a,b,c,d <.001 COMP 20.9 ± ± ± ± 7.4 a 31.4 ± 8.7 a,b,c 38.5 ± 14.2 a,b,c,d,e <.001 KURT 2.71 ± ± ± ± ± ± 1.08 e.059 SKEW 0.21 ± ± ± ± 0.16 a,b 0.43 ± 0.12 a,b,c 0.65 ± 0.35 a,b,c,d,e <.001 CONT 171 ± ± ± ± 59 a,b,c 242 ± 37 a,b,c 261 ± 55 a,b,c <.001 ENT 3.88 ± ± ± ± ± ± 0.16 d.049 IDM ± ± a ± ± ± a ± a,b,c,d <.001 ASM ± ± ± ± ± a,b,c ± a,b,c,d,e <.001 CORR ± ± a ± a ± ± a,c,d ± a <.001 Liver fibrosis index 2.57 ± ± ± 0.90 a 3.84 ± 0.78 a,b,c 4.21 ± 0.65 a,b,c 4.79 ± 0.86 a,b,c,d,e <.001 Stiffness, kpa 4.09 ± ± ± ± 7.87 a,b,c ± a,b,c,d ± a,b,c,d,e <.001 Data are expressed as mean ± SD. Abbreviations are as in Table 4. a P <.05 versus control; b P <.05 versus F0; c P <.05 versus F1; d P <.05 versus F2; e P <.05 versus F3. J Ultrasound Med 2015; 34:

6 Discussion Identification of liver fibrosis stages is important in the clinical management of chronic hepatitis because the treatment and prognosis of chronic hepatitis depend on the extent and progression of the hepatic fibrosis. Several noninvasive methods such as routine laboratory tests, serum fibrosis markers, transient elastography (FibroScan), and real-time tissue elastography have been developed for diagnosis of hepatic fibrosis. This study mainly focused on comparisons between real-time tissue elastography and FibroScan. Our study shows that the measurements from both real-time tissue elastography and FibroScan are closely correlated with histologic liver fibrosis stages. The two methods have a similar ability for discriminating hepatic fibrosis and show high diagnostic accuracy. Transient Elastography FibroScan consists of an ultrasound transducer that produces a vibration with a low frequency and mild amplitude. The vibration induces an elastic shear wave that propagates through the liver. 31 The propagation velocity of the shear wave is proportional to the liver tissue stiffness and is used as an indicator of hepatic fibrosis. 32 Consistent with our study, a number of researches have demonstrated that FibroScan measurements are significantly correlated with the histological fibrosis stage and have high diagnostic accuracy for discriminating hepatic fibrosis in patients with chronic hepatitis B. 6 9 The AUCs of FibroScan ranged from 0.81 to 0.95, with a cutoff value of 6.3 to 7.9 kpa for assessment of substantial fibrosis. 9 FibroScan has been considered to have acceptable diagnostic accuracy in patients with chronic hepatitis B. 6 Figure 2. Receiver operating characteristic curves for the liver fibrosis index from real-time tissue elastography and liver stiffness from transient elastography for diagnoses of substantial fibrosis ( F2; A), severe fibrosis ( F3; B), and cirrhosis (F4; C). Table 6. Results for the Liver Fibrosis Index Obtained via Real-time Tissue Elastography and Liver Stiffness Obtained via FibroScan for Determination of the Liver Fibrotic Stage Liver Fibrosis Index Liver Stiffness Parameter F2 F3 F4 F2 F3 F4 AUC Optimal cutoff kpa kpa kpa Sensitivity, % Specificity, % Positive predictive value, % Negative predictive value, % J Ultrasound Med 2015; 34:

7 However, there are some confounding factors that can influence FibroScan measurements. In patients with acute flares of chronic hepatitis B, FibroScan should not be performed unless alanine aminotransferase levels are stabilized because the extent of necroinflammatory activity has been known to influence FibroScan measurements. 33 FibroScan is also impossible in patients with ascites, since shear waves do not propagate in liquid. In addition, it is difficult in patients with a high body mass index or narrow intercostal spaces. 28,29 Recently, a new FibroScan probe (XL probe) has been developed to lessen the failure rate in obese patients, and its good efficacy has been shown in some investigations. 26,27 Real-time Tissue Elastography Real-time tissue elastography is a novel method for assessing tissue elasticity. It calculates the strain of the examined structures and displays the relative hardness of tissue as real-time color images using conventional ultrasound equipment. The tissue elasticity distribution and conventional B-mode images can be visualized at the same time. 17 Moreover, in this study, a new method was applied to quantitatively evaluate hepatic elasticity with 11 parameters characterizing tissue stiffness in the ROI. Four independent predictors were selected by a stepwise multivariate regression analysis of these 11 parameters to define the liver fibrosis index. The liver fibrosis index formula derived in this study is different from those in other studies. 10,12,14 In those studies, patients with chronic hepatitis C were included, and the liver fibrosis index was estimated by using 9 image variables as independent predictors. Real-time tissue elastography has been regarded as a promising technique capable of noninvasive evaluation of fibrosis with high diagnostic accuracy in patients with diffuse liver disease Tatsumi et al 13 found that the levels of liver strain measured by real-time tissue elastography correlated well with liver stiffness in patients with chronic liver disease. Koizumi et al 11 reported that the liver elasticity derived from real-time tissue elastography was significantly related to the fibrosis stage and performed better than serum fibrosis markers for diagnosis of liver fibrosis in patients with chronic hepatitis C. Also, real-time tissue elastography has successfully been used in patients with chronic hepatitis B. 34 Comparisons Between Real-time and Transient Elastography Our results showed that both real-time tissue elastography and transient elastography (FibroScan) were useful for noninvasive evaluation of liver fibrosis, with comparable diagnostic performance. However, considering the unfavorable conditions limiting the application of FibroScan, real-time tissue elastography seems to be a better test than FibroScan. One advantage of real-time tissue elastography is that it is integrated into a conventional ultrasound system and is performed with conventional probes. Therefore, it can be performed during routine sonographic examinations without any need for additional equipment. In addition, only an M-mode image can be obtained in FibroScan to localize the optimal measurement site, whereas placement of the ROI in real-time tissue elastography is relatively easy on a conventional B-mode image, and interfering structures such as blood vessels can be avoided. 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