Supersonic Shear Wave Imaging of the Spleen for Staging of Liver Fibrosis in Rats

The goal of the work described here was to explore the cause of spleen stiffness (SS) in hepatic fibrogenesis and evaluate the value of SS in liver fibrosis (LF) staging. LF was induced with carbon tetrachloride (CCl₄) in rats (n = 40). Supersonic shear wave imaging and contrast-enhanced ultrasound were performed to determine liver stiffness (LS), SS and splenic hemodynamics. SS, LS and free portal pressure exhibited moderate correlations with fibrosis stage (r = 0.744–0.835, p < 0.001). Time–intensity curves of contrast-enhanced ultrasound for the spleen were presented as decreasing peak intensity and slope of decrease, and increasing time to peak. Splenic sinus dilation and congestion were observed on histopathologic analysis. The area under the receiver operating characteristic curve of SS was higher than that of LS for differentiating LF stages 0–2 from stages 3–4 (Z = 2.293, p = 0.02). SS is a reliable diagnostic marker for the assessment of LF in the CCl₄ model, especially for severe fibrosis. Elevated portal pressure is the cause of increasing SS.     

Acoustic Radiation Force Impulse and Supersonic Shear Imaging Versus Transient Elastography for Liver Fibrosis Assessment

Our study compared three elastographic methods—transient elastography (TE), acoustic radiation force impulse (ARFI) imaging and supersonic shear imaging (SSI)—with respect to the feasibility of their use in liver fibrosis evaluation. We also compared the performance of ARFI imaging and SSI, with TE as the reference method. The study included 332 patients, with or without hepatopathies, in which liver stiffness was evaluated using TE, ARFI and SSI. Reliable measurements were defined as a median value of 10 (TE, ARFI imaging) or 5 (SSI) liver stiffness measurements with a success rate ≥60% and an interquartile range interval <30%. A significantly higher percentage of reliable measurements were obtained using ARFI than by using TE and SSI: 92.1% versus 72.2% (p < 0.0001) and 92.1% versus 71.3% (p < 0.0001). Higher body mass index and older age were significantly associated with inability to obtain reliable measurements of liver stiffness using TE and SSI. In 55.4% of patients, reliable liver stiffness measurements were obtained using all three elastographic methods, and ARFI imaging and TE were similarly accurate in diagnosing significant fibrosis and cirrhosis, with TE as the reference method.     

Shear Wave Elastography for Evaluation of Liver Fibrosis

The prognosis and management of chronic viral hepatitis mainly depend on the extent of liver fibrosis, particularly in chronic hepatitis C. Liver histologic analysis is still considered the reference standard in the assessment of liver fibrosis despite the interobserver and interobserver variability in staging and some morbidity and mortality risks. Thus, noninvasive methods for assessing liver fibrosis are of great clinical interest. In the last decade, ultrasound‐based techniques to estimate the stage of liver fibrosis have become commercially available. They all have the capability to noninvasively evaluate differences in the elastic properties of soft tissues by measuring tissue behavior when a mechanical stress is applied. Shear wave elastography relies on the generation of shear waves determined by the displacement of tissues induced by the force of a focused ultrasound beam or by an external push. This article reviews the results that have been obtained with shear wave elastography for assessment of liver fibrosis.     

Diagnostic Accuracy of 2-D Shear Wave Elastography for the Non-Invasive Staging of Liver Fibrosis in Patients with Elevated Alanine Aminotransferase Levels

This study assessed the diagnostic accuracy of 2-D shear wave elastography (2-D-SWE) for the non-invasive staging of liver fibrosis and compared the findings with those for biochemical markers (the aspartate aminotransferase-to-platelet index and fibrosis-4 index) of liver fibrosis in patients with elevated alanine aminotransferase (ALT) levels (>5?×?the upper limit of normal). Patients with chronic liver diseases and elevated ALT levels who underwent liver biopsy were consecutively included. Receiver operating characteristic (ROC) curves were constructed to assess overall accuracy and to identify optimal cutoff values. After exclusions, data from 105 patients were analyzed. The areas under the ROC curves (AUROCs) for significant fibrosis, severe fibrosis and cirrhosis were 0.83, 0.86 and 0.91, respectively. The optimal cutoff values for predicting significant fibrosis, severe fibrosis and cirrhosis were 10.6, 13.2 and 17.6?kPa, respectively. The AUROCs of 2-D-SWE were significantly higher than those of biochemical markers for predicting significant fibrosis, severe fibrosis and cirrhosis (all p values?<?0.05). Therefore, the diagnostic performance of 2-D-SWE in assessing liver fibrosis stages in patients with elevated ALT levels was promising. The optimal cutoff values were increased but appropriate for this cohort because the baseline levels of liver stiffness measurements were increased in these patients, even in the absence of fibrosis.     

超声弹性成像评价肝纤维化程度的初步探讨

目的 探讨超声弹性成像在评价肝纤维化程度中的应用价值.方法 慢性乙型肝炎患者50例,进行肝穿前作超声弹性成像评分,分为1～4分,将肝组织纤维化病理分期与超声弹性成像评分进行对比分析.结果 超声弹性成像评分与肝组织纤维化病理分期的相关系数为0.813(P=0.000),超声弹性成像评分随肝纤维化程度的上升而增高.肝纤维化S4期作为早期肝硬化诊断指标,通过ROC曲线分析超声弹性成像评分曲线下面积为0.883(P=0.000),敏感性88.9%、特异性95.1%.结论 超声弹性成像在评价肝纤维化程度中具有独特优势和广阔的应用前景.     

Comparison of 2-D Shear Wave Elastography and Transient Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B

This study compared 2-D shear wave elastography (SWE) and transient elastography (TE) for liver fibrosis staging in patients with chronic hepatitis B (CHB) infection using liver biopsy as the reference standard. Patients with CHB infection who underwent liver biopsy were consecutively included. After exclusions, 257 patients were analyzed. Two-dimensional SWE resulted in a significantly higher rate of reliable measurements (98.1%, 252/257) than TE (93.0%, 239/257) (p = 0.011). Liver stiffness measurements of the two examinations exhibited a strong correlation (r = 0.835, p < 0.001). In patients given a confirmed histologic diagnosis, Spearman's rank coefficients were 0.520 in stage F0 (p < 0.001), 0.684 in stage F1 (p < 0.001), 0.777 in stage F2 (p < 0.001), 0.672 in stage F3 (p < 0.001) and 0.755 in stage F4 (p < 0.001). There were no significant differences between the areas under the receiver operating characteristic (ROC) curves of 2-D SWE and TE for liver fibrosis staging (all p values > 0.05). Two-dimensional SWE had diagnostic accuracy comparable to that of TE for liver fibrosis staging. The measurements that the two techniques provide are not interchangeable.     

Non-invasive Assessment of Liver Fibrosis in a Rat Model: Shear Wave Elasticity Imaging Versus Real-Time Elastography

The purpose of this study was to investigate the diagnostic value of shear wave elasticity imaging (SWEI) and real-time elastography (RTE) in liver fibrosis induced by dimethylnitrosamine (DMN) and to compare the accuracy of these methods. Seventy male Wistar rats given a single intra-peritoneal injection of DMN and 10 control rats given a saline injection underwent SWEI and RTE to determine their shear wave velocity (V_s) and liver fibrosis (LF) index, respectively. Correlations between V_s or the LF index and histologic stage of liver fibrosis (S0–S4) were analyzed, and the diagnostic values of the techniques were assessed using a receiver operating characteristic curve. A positive correlation was found between V_s and stage of liver fibrosis (r = 0.947, p < 0.001) and between LF index and stage (S) of liver fibrosis (r = 0.662, p < 0.001). For V_s, the areas under the receiver operating characteristic curve for the diagnosis of fibrosis, S ≥ S1, S ≥ S2, S ≥ S3 and S = S4, were 0.983, 0.995, 0.999 and 0.964, respectively; for the LF index, the values were 0.871, 0.887, 0.761 and 0.839, respectively (all p < 0.001). V_s and the LF index values in rats with severe inflammatory activity were significantly higher than those in controls (p < 0.001). In conclusion, positive correlations exist between V_s or the LF index and the severity of liver fibrosis in rats. V_s is more accurate than the LF index in predicting liver fibrosis in rats. However, severe inflammatory activity may reduce the accuracy of both techniques.     

Point Shear Wave Elastography for Non-invasive Assessment of Liver Fibrosis in Patients with Viral Hepatitis

Elastography point quantification (ElastPQ) is a new ultrasound-based shear wave elastography method for non-invasive assessment of liver fibrosis. We evaluated the diagnostic accuracy of ElastPQ in patients with chronic viral hepatitis. Fibrosis stage (F) was determined by transient elastography (F0/F1: <7.1 kPa, F2: 7.1–9.4 kPa, F3: 9.5–12.4 kPa, F4: ≥12.5 kPa). Area under the receiver operator characteristics curve (AUROC) analysis was performed to assess ElastPQ cutoffs for significant fibrosis (≥F2) and cirrhosis (F4). Paired transient elastography and ElastPQ measurements were obtained from 217 patients (mean age ± SEM: 49 ± 0.79 years, 68.2% male, F0/F1: n?=?98 [45.0%], F2: 47 [21.6%], F3: 22 [10.1%], F4: 50 [22.9%]). AUROC for ≥F2 was 0.843 (95% confidence interval: 0.791–0.895), and for F4, 0.933 (95% confidence interval: 0.894–0.972). The optimal ElastPQ cutoff for F2 was 6.68 kPa (sensitivity: 80.7%, specificity: 70.4%, positive predictive value: 78.5%, negative predictive value: 72.3%), and for F4 11.28 kPa (sensitivity: 86.0%, specificity: 85.6%, positive predictive value: 60.52%, negative predictive value: 97.16%). In conclusion, ElastPQ represents an accurate tool for non-invasive staging of liver fibrosis in patients with viral hepatitis.     

Liver Stiffness Measurements by Means of Supersonic Shear Imaging in Patients Without Known Liver Pathology

We used supersonic shear imaging to determine the liver stiffness (LS) values of 82 patients without known liver pathology and studied the factors that influence these measurements. Five LS measurements were made in each subject, and the median value, expressed in kilopascals, was calculated. Reliable LS measurements were obtained in 84.5% of patients. Higher body mass index and older age were associated with failure to obtain reliable measurements. The mean value of LS measurements determined by SSI in our cohort of patients without known liver pathology was 6 ± 1.4 kPa. The mean LS measurements determined by SSI for men were significantly higher than those for women; body mass index did not significantly influence SSI measurements. Thus, 6 kPa is the mean SSI value in patients without known liver pathology, with higher values being obtained in men.     

On Patient Related Factors and Their Impact on Ultrasound-Based Shear Wave Elastography of the Liver

The aim of the study was to investigate patient-related factors associated with either reliable or poorly reliable measurement results of ultrasound-based shear wave elastography (SWE) of the liver. A total of 188 patients were analyzed prospectively with binary logistic regression using the interquartile range/median as cutoff to define two groups based on reliable and poorly reliable SWE results. SWE results correlated significantly with liver biopsy. Factors associated with reliable SWE results (i.e., no negative impact on measurements) were age, sex, cirrhosis, antiviral and/or cardiovascular medication, smoking habits and body mass index. Factors associated with poorly reliable SWE results were increased skin-to-liver capsule distance (odds ratio?=?3.08, 95% confidence interval: 1.70–5.60) and steatosis (odds ratio?=?2.89, 95% confidence interval: 1.33–6.28). These findings indicate that the interquartile range/median as a quality parameter is useful in avoiding poorly reliable SWE results. How best to examine patients with increased skin-to-liver capsule distance is a matter of some controversy, as the incidences of obesity, diabetes and metabolic syndrome are increasing worldwide; however, our results indicate that reliable SWE results can be obtained in this group of patients by using ultrasound-based SWE.     

Normal Liver Stiffness in Healthy Adults Assessed By Real-Time Shear Wave Elastography and Factors That Influence This Method

Real-time shear wave elastography (SWE) is a novel two-dimensional elastographic method that is used to estimate the severity of liver fibrosis. However, the normal range of liver stiffness (LS) and the possible factors that influence SWE are not well understood. The aims of the current study are to define the normal range of LS in healthy subjects and to explore the factors that may affect SWE. A total of 509 healthy subjects underwent SWE to determine the stiffness of their livers, and the effects of gender, age and body mass index (BMI) on LS were analyzed. The effects of different factors on SWE, including the testing position, measurement depth and size of the region of interest (ROI), were analyzed in 137 subjects. SWE imaging was successfully performed in 502 healthy subjects (98.6%, 502/509). The mean value of the SWE measurements in 502 individuals was 5.10 ± 1.02 kPa, and the 95% confidence interval was 5.02–5.19 kPa (range: 2.4–8.7 kPa). We found that the detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V. LS was greater at a depth >5 cm (5.78 ± 1.66 kPa) compared with depths ≤5 cm (4.66 ± 0.77 kPa, p < 0.001); LS was also greater in men than in women (5.45 ± 1.02 kPa vs. 4.89 ± 0.96 kPa, p < 0.001). However, there were no significant differences in the LS values regarding the size of the ROI, age or BMI (all p > 0.05). The mean LS value in all 502 healthy subjects was 5.10 ± 1.02 kPa. The mean LS value obtained by SWE was not influenced by the size of the ROI, age or BMI, but the mean value was significantly influenced by the different segments of the liver, the detection depth and gender.     

Assessing Hepatic Fibrosis Using 2-D Shear Wave Elastography in Patients with Liver Tumors: A Prospective Single-Center Study

The purpose of this study was to investigate the diagnostic performance of 2-D shear wave elastography (2-D-SWE) in evaluations of liver stiffness in patients with liver tumors before resection. A total of 121 consecutive patients with hepatocellular carcinoma (HCC) (n = 93), intra-hepatic cholangiocarcinoma (n = 6), mixed hepatocellular carcinoma and intra-hepatic cholangiocarcinoma (n = 6), liver metastases (n = 10) and benign tumors (n = 6) were prospectively enrolled in this study from June 2015 to March 2016. Three valid 2-D-SWE measurements for each patient and median liver stiffness values were calculated. Fibrosis staging was evaluated according to the METAVIR scoring system. A receiver operating characteristic curve analysis was used to assess diagnostic performance. In this study, we found that median liver stiffness values were significantly higher in patients with primary liver tumors than in those with liver metastases and benign tumors (11.80 kPa vs. 5.85 kPa, p < 0.001). In addition, liver stiffness, assessed using 2-D-SWE, was highly correlated with pathologically confirmed liver fibrosis stage. Liver fibrosis stage and liver stiffness values were analyzed using Spearman's correlation (0.708, p < 0.001). The median liver stiffness values were as follows: F1, 6.7 kPa; F2, 6.33 kPa; F3, 9.2 kPa; F4, 13.7 kPa. The area under the receiver operating characteristic curves of the liver stiffness values that predicted significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4) were 83.5%, 91.6% and 88.1%, respectively. According to the Youden index, the optimal cutoff values for predicting significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4) were 7.05 kPa (sensitivity = 74.6%, specificity = 100.0%), 9.45 kPa (sensitivity = 78.8%, specificity = 100.0%) and 11.1 kPa (sensitivity = 83.1%, specificity = 89.3%), respectively. We conclude that 2-D-SWE is a useful, accurate and non-invasive method for evaluating hepatic fibrosis in patients with liver tumors adapted to hepatectomy (ClinicalTrials.gov ID: NCT02958592).     

Intra-Individual Comparison between 2-D Shear Wave Elastography (GE System) and Virtual Touch Tissue Quantification (Siemens System) in Grading Liver Fibrosis

Ultrasound-based shear wave elastography (SWE) has recently gained substantial attention for non-invasive assessment of liver fibrosis. The purpose of this study was to perform an intra-individual comparison between 2-D shear wave elastography (2-D-SWE with a GE system) and Virtual Touch Tissue Quantification (VTTQ with a Siemens system) to assess whether these can be used interchangeably to grade fibrosis. Ninety-three patients (51 men, 42 women; mean age, 54 y) with liver disease of various etiologies (hepatitis B virus?=?47, hepatitis C virus?=?22; alcohol?=?6, non-alcoholic steatohepatitis?=?5, other?=?13) were included. Using published system-specific shear wave speed cutoff values, liver fibrosis was classified into clinically non-significant (F0/F1) and significant (≥F2) fibrosis. Results indicated that intra-modality repeatability was excellent for both techniques (GE 2-D-SWE: intra-class correlation coefficient?=?0.89 [0.84–0.93]; VTTQ: intra-class correlation coefficient?=?0.90 [0.86–0.93]). Intra-modality classification agreement for fibrosis grading was good to excellent (GE 2-D-SWE: κ?=?0.65, VTTQ: κ?=?0.82). However, inter-modality agreement for fibrosis grading was only fair (κ?=?0.31) using published system-specific shear wave speed cutoff values of fibrosis. In conclusion, although both GE 2-D-SWE and Siemens VTTQ exhibit good to excellent intra-modality repeatability, inter-modality agreement is only fair, suggesting that these should not be used interchangeably.     

Acoustic Structure Quantification Versus Point Shear Wave Speed Measurement for the Assessment of Liver Fibrosis in Viral Hepatitis B

This study was conducted to evaluate the value of acoustic structure quantification (ASQ) technology versus that of point shear wave speed measurement (PSWSM) imaging technology for the assessment of liver fibrosis stage. A total of 104 patients with chronic hepatitis B (CHB) and 30 healthy control patients underwent ASQ and PSWSM examinations. Seven quantitative parameters were obtained from ASQ, and a principal component analysis was used to establish the integrative indicators. A quantitative parameter, known as the shear wave speed (SWS, m/s), was obtained from the PSWSM. The METAVIR scores for the assessment of pathologic liver fibrosis were used as a benchmark. Liver fibrosis stages exhibited a good correlation with the integrative indicators and SWS (r?=?0.682, p?<0.001; r?=?0.651, p?<0.001). The areas under the receiver operating characteristic curves for ASQ and PSWSM were 0.705 and 0.854 for mild liver fibrosis (F?≥?1, p?=?0.045), 0.813 and 0.743 for significant liver fibrosis (F?≥?2, p?=?0.115), 0.839 and 0.857 for severe liver fibrosis (F?≥?3, p?=?0.417) and 0.874 and 0.971 for liver cirrhosis (F?=?4, p?=?0.016), respectively. In conclusion, both ASQ and PSWSM were promising ultrasonic methods for assessing liver fibrosis in patients with CHB; however, PSWSM was more valuable for identifying mild liver fibrosis (F?≥?1) and cirrhosis (F?=?4) than ASQ, and the combination of PSWSM and ASQ improved the accuracy of diagnosing severe liver fibrosis (F?≥?3).     

Real-Time Elastography in the Assessment of Liver Fibrosis: A Review of Qualitative and Semi-quantitative Methods for Elastogram Analysis

Despite its invasiveness, liver biopsy is still considered the gold standard for the assessment of hepatic fibrosis. Non-invasive ultrasound-based techniques are increasingly employed to assess parenchymal stiffness and the progression of chronic diffuse liver diseases. Real-time elastography is a rapidly evolving technique that can reveal the elastic properties of tissues. This review examines qualitative and semi-quantitative methods developed for analysis of real-time liver elastograms, to estimate parenchymal stiffness and, indirectly, the stage of fibrosis. Qualitative analysis is the most immediate approach for elastogram analysis, but this method increases intra- and inter-observer variability, which is seen as a major limitation of real-time elastography. Semi-quantitative methods include analysis of the histogram derived from color-coded maps, as well as calculation of the elastic ratio and fibrosis index.     

Quantitative Shear Wave Elastography in the Evaluation of Metastatic Cervical Lymph Nodes

Our aim was to compare the diagnostic performance of shear wave elastography (SWE) with that of gray-scale ultrasound (US) in differentiating metastatic from benign lymph nodes in patients with head and neck malignancies. Maximum shear elasticity modulus (maxSM) was measured on SWE. The reference standard was pathologic diagnosis after surgery. We examined 67 lymph nodes (34 metastatic, 33 benign) from 15 patients (8 men and 7 women; mean age, 54.2 years). The maxSM value was significantly higher for metastatic than benign lymph nodes (41.06 ± 36.34 kPa vs. 14.22 ± 4.19 kPa, p < 0.0001) at a cutoff level of 19.44 kPa. Accuracy, sensitivity and specificity were 94, 91 and 97%, respectively, for SWE, and 91, 88 and 94%, respectively, for gray-scale US. Multiple regression analysis showed that the maxSM value (r = 0.882) and gray-scale US criteria (r = 0.837) were independent variables. SWE may be a valuable quantitative reproducible method for characterizing cervical lymph nodes.     

Inter- and Intra-Operator Reliability and Repeatability of Shear Wave Elastography in the Liver: A Study in Healthy Volunteers

This study assessed the reproducibility of shear wave elastography (SWE) in the liver of healthy volunteers. Intra- and inter-operator reliability and repeatability were quantified in three different liver segments in a sample of 15 subjects, scanned during four independent sessions (two scans on day 1, two scans 1 wk later) by two operators. A total of 1440 measurements were made. Reproducibility was assessed using the intra-class correlation coefficient (ICC) and a repeated measures analysis of variance. The shear wave speed was measured and used to estimate Young's modulus using the Supersonics Imagine Aixplorer. The median Young's modulus measured through the inter-costal space was 5.55 ± 0.74 kPa. The intra-operator reliability was better for same-day evaluations (ICC = 0.91) than the inter-operator reliability (ICC = 0.78). Intra-observer agreement decreased when scans were repeated on a different day. Inter-session repeatability was between 3.3% and 9.9% for intra-day repeated scans, compared with to 6.5%–12% for inter-day repeated scans. No significant difference was observed in subjects with a body mass index greater or less than 25 kg/m².