Wenwu Ling

Assessment of impact factors on shear wave based liver stiffness measurement

Shear wave based ultrasound elastographies have been implemented as non-invasive methods for quantitative assessment of liver stiffness. Nonetheless, there are only a few studies that have investigated impact factors on liver stiffness measurement (LSM). Moreover, standard examination protocols for LSM are still lacking in clinical practice. Our study aimed to assess the impact factors on LSM to establish its standard examination protocols in clinical practice. We applied shear wave based elastography point quantification (ElastPQ) in 21 healthy individuals to determine the impact of liver location (segments I-VIII), breathing phase (end-inspiration and end-expiration), probe position (sub-costal and inter-costal position) and examiner on LSM. Additional studies in 175 healthy individuals were also performed to determine the influence of gender and age on liver stiffness. We found significant impact of liver location on LSM, while the liver segment V displayed the lowest coefficient of variation (CV 21%). The liver stiffness at the end-expiration was significantly higher than that at the end-inspiration (P=2.1E-05). The liver stiffness was 8% higher in men than in women (3.8 ± 0.7 kPa vs. 3.5 ± 0.4 kPa, P=0.0168). In contrast, the liver stiffness was comparable in the different probe positions, examiners and age groups (P>0.05). In conclusion, this study reveals significant impact from liver location, breathing phase and gender on LSM, while furthermore strengthening the necessity for the development of standard examination protocols on LSM.

Stiffness Value and Serum Biomarkers in Liver Fibrosis Staging: Study in Large Surgical Specimens in Patients with Chronic Hepatitis B

Purpose To investigate the capabilities of stiffness value and serum biomarkers in the staging of liver fibrosis in patients with chronic hepatitis B (CHB), with pathologic findings in large surgical specimens serving as the reference standard. Materials and Methods This study was approved by the institutional review board, and informed consent was obtained from all patients. Liver stiffness (determined by means of ultrasonography-based elastography point quantification), aspartate aminotransferase-platelet ratio index (APRI), and fibrosis index (based on the four-factor Fibrosis-4 [FIB-4] calculation) were obtained in 386 patients with CHB. With pathologic fibrosis stages in large surgical specimens as the reference standard, capabilities and cutoffs of stiffness and serum biomarkers were first investigated in a cohort of 284 patients and then validated in an independent cohort of 102 patients by means of area under the receiver operating characteristic curve (AUC) analysis. Results Liver stiffness demonstrated significantly stronger correlation with fibrosis stages than did APRI and FIB-4 (r = 0.738 vs r = 0.477 vs r = 0.427, respectively; P < .05 for all). In the development cohort, liver stiffness had significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.97, 0.96, 0.91, and 0.87, respectively) than APRI (0.89, 0.84, 0.73, and 0.74, respectively) and FIB-4 (0.82, 0.79, 0.70, and 0.72, respectively). In the validation cohort, liver stiffness was validated as showing significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.99, 0.95, 0.89, and 0.88, respectively) than APRI (0.83, 0.76, 0.78, and 0.68, respectively) and FIB-4 (0.76, 0.69, 0.75, and 0.67, respectively). Conclusion Liver stiffness demonstrated considerable capability in identifying each stage of liver fibrosis in patients with CHB, whereas serum biomarkers showed limited capabilities. (©) RSNA, 2016 Online supplemental material is available for this article.

Hepatocellular Carcinoma: Stiffness Value and Ratio to Discriminate Malignant from Benign Focal Liver Lesions

PURPOSE To investigate the use of stiffness value and stiffness ratio (ratio of lesion to background liver parenchyma values) to discriminate malignant from benign focal liver lesions by using histologic results as the reference standard. MATERIALS AND METHODS This study was approved by the institutional review board, and written informed consent was obtained. Three hundred seventy-three patients with focal liver lesions proven at histologic examination underwent measurement of liver stiffness with elastography point quantification. First, stiffness values in two regions of the background liver parenchyma (at 0.5-2 cm and >2 cm from the lesion periphery) near 163 hepatocellular carcinomas were analyzed to determine a reference background liver for calculating the stiffness ratio. Second, the use of the lesion stiffness value and the stiffness ratio for prediction of liver malignancy was investigated in a cohort of patients with 58 benign and 201 malignant lesions. Results were validated in another independent cohort of patients with 25 benign and 89 malignant lesions by using analysis of the area under the receiver operating characteristic (AUC) curve. RESULTS The coefficient of variation for the background liver at 0.5-2 cm from the lesion was higher (196%) than that at greater than 2 cm from the lesion (66%). In the development phase, diagnostic accuracy with use of the stiffness value was significantly higher than that with use of the stiffness ratio for discrimination of malignant from benign lesions (AUC, 0.86 vs 0.66, respectively; P < .001). Diagnostic performance with the stiffness value was lower than that with the stiffness ratio (AUC, 0.53 vs 0.86, respectively; P < .001) for discrimination of cirrhotic nodules from other benign lesions. Diagnostic performance with the stiffness value was significantly lower than that with the stiffness ratio (AUC, 0.58 vs 0.71 respectively; P = .007) for discrimination of metastasis from primary liver cancers. In the validation phase, similar findings were revealed for the discrimination of malignant from benign lesions (AUC, 0.87 vs 0.67; P < .001) and discrimination between metastasis and primary liver cancers (AUC, 0.49 vs 0.73; P < .001). CONCLUSION Use of stiffness values measured in the liver parenchyma at more than 2 cm from the lesion allowed better diagnostic performance than did values measured in a region closer to the tumor. Stiffness value was more accurate than stiffness ratio for differentiation of malignant from benign focal liver lesions, but the stiffness ratio might be useful for subclassification of benign and malignant lesions. Online supplemental material is available for this article.

Effects of Vascularity and Differentiation of Hepatocellular Carcinoma on Tumor and Liver Stiffness: In Vivo and in Vitro Studies

Tissue stiffness has been found to be a useful predictor of malignancy in various cancers. However, data on the stiffness of hepatocellular carcinomas (HCCs) and their background livers are contradictory. The aim of this study was to investigate the effects of vascularity and histologic differentiation on HCC stiffness. Elastography point quantification (ElastPQ), a new shear wave-based elastography method, was used to measure liver stiffness in vivo in 99 patients with pathology-proven HCC. Lesion vascularity was assessed using contrast-enhanced ultrasound, computed tomography and/or magnetic resonance imaging. The association of HCC vascularity and differentiation with liver stiffness was determined. In addition, in vitro stiffness of 20 of the 99 surgical HCC specimens was mechanically measured and compared with in vivo measurements. We found that in vivo stiffness was significantly higher than in vitro stiffness in both HCCs and their background livers (p < 0.0001). Moreover, significantly higher stiffness was observed in hyper-vascular and poorly differentiated lesions than in hypo-vascular (p = 0.0352) and moderately to well-differentiated lesions (p = 0.0139). These in vivo and in vitro studies reveal that shear wave-based ultrasound elasticity quantification can effectively measure in vivo liver stiffness.

Contrast-enhanced ultrasonographic findings of hepatic paragonimiasis

AIM To investigate the features of hepatic paragonimiasis on contrast-enhanced ultrasound (CEUS) imaging. METHODS Fifteen patients with hepatic paragonimiasis who were admitted to our hospital between March 2008 and August 2012 were enrolled to this study. The conventional ultrasound and CEUS examinations were performed with a Philips IU22 scanner with a 1-5-MHz convex transducer. After conventional ultrasound scanning was completed, the CEUS study was performed. Pulse inversion harmonic imaging was used for CEUS. A bolus injection of 2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent (SonoVue) was administered. CEUS features were retrospectively reviewed and correlated with pathological findings. RESULTS In total, 16 lesions were detected on CEUS. The mean size of the lesions was 4.4 ± 1.6 cm (range, 1.7-6.6 cm). Subcapsular location was found in 12 lesions (75%). All the lesions were hypoechoic. Six lesions (37.5%) were of mixed content, seven (43.8%) were solid with small cystic areas, and the other three (18.8%) were completely solid. Ten lesions (62.5%) were rim enhanced with irregular tract-like nonenhanced internal areas. Transient wedge-shaped hyperenhancement of the surrounding liver parenchyma was seen in seven lesions (43.8%). Areas with hyper- or iso-enhancement in the arterial phase showed contrast wash-out and appeared hypoenhanced in the late phase. The main pathological findings included: (1) coagulative or liquefactive necrosis within the lesion, infiltration of a large number of eosinophils with the formation of chronic eosinophilic abscesses and sporadic distribution of Charcot-Leyden crystals; and (2) hyperplasia of granulomatous and fibrous tissue around the lesion. CONCLUSION Subcapsular location, hypoechogenicity, rim enhancement and tract-like nonenhanced areas could be seen as the main CEUS features of hepatic paragonimiasis.

Contrast-enhanced ultrasound in diagnosis of primary hepatic angiosarcoma

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor that occurs mainly in the elderly, with almost no specific symptoms or tumor markers. Information on the imaging characteristics of this tumor is limited due to its rarity. Therefore, it is difficult to diagnose PHA. So far, its definite diagnosis depends on histopathologic examination combined with immunohistochemical results. Patients with PHA have a poor prognosis in spite of surgical resection of this tumor. In this case report, we present a 72-year-old woman with PHA, focusing on the imaging features of this tumor, especially its enhancement pattern on contrast-enhanced ultrasound images. Contrast-enhanced ultrasound provided helpful information for diagnosis.

The preliminary application of liver imaging reporting and data system (LI-RADS) with contrast-enhanced ultrasound (CEUS) on small hepatic nodules (≤ 2cm)

To evaluate the diagnostic accuracy of liver imaging reporting and data system (LI-RADS) with contrast-enhanced ultrasound (CEUS) for patients at risk for hepatocellular carcinoma with hepatic nodules (≤2cm). We retrospectively evaluated 56 CEUS exam records of hepatic nodules (≤2cm) performed between January 2015 and July 2016 at West China hospital. Each nodule was classified into a LI-RADS-CEUS category by two radiologists according to imaging features. The ultimate CEUS categories were then compared with pathological reports and their correlation was then calculated. Inter-observer agreement for LI-RADS between reader A and B was κ, 0.690, illustrating good consistency. The diagnostic accuracy of LR-5 on hepatocellular carcinoma (HCC) was 86.49% but 11.11% for LR-M. LI-RADS-CEUS is a potential standardized categorization system for high-risk HCC patients but might also increase the false-negative diagnosis of nodules of less than 2cm.

Grading fatty liver by ultrasound time-domain radiofrequency signal analysis: an in vivo study of rats

This study aimed to assess the severity of fatty liver (FL) by analyzing ultrasound radiofrequency (RF) signals in rats. One hundred and twenty rats (72 in the FL group and 48 in the control group) were used for this purpose. Histological results were the golden standard: 42 cases had normal livers (N), 30 cases had mild FL (L1), 25 cases had moderate FL (L2), 13 cases presented with severe FL (L3), and 10 cases were excluded from the study. Four RF parameters (Mean, Mean/SD ratio [MSR], skewness [SK], and kurtosis [KU] were extracted. Univariate analysis, spearman correlation analysis, and stepwise regression analysis were used to select the most powerful predictors. Receiver operating characteristic (ROC) analysis was used to compare the diagnostic efficacy of single indexes with a combined index (Y) expressed by a regression equation. Mean, MSR, SK, and KU were significantly correlated with FL grades (r=0.71, P<0.001; r=0.81, P<0.001; r=−0.79, P<0.001; and r=−0.74, P<0.001). The regression equation was Y=−4.48 + 3.20 × 10−2X1 + 3.15X2 (P<0.001), where Y=hepatic steatosis grade, X1 =Mean, and X2 =MSR. ROC analysis showed that the curve areas of the combined index (Y) were superior to simple indexes (Mean, MSR, SK, and KU) in evaluating hepatic steatosis grade, and they were 0.95 (L≥L1), 0.98 (L≥L2), and 0.99 (L≥L3). Ultrasound radiofrequency signal quantitative technology was a new, noninvasive, and promising sonography-based approach for the assessment of FL.

Can ultrasound elastography identify mass-like focal fatty change (FFC) from liver mass?

Abstract Focal fatty change (FFC) may mimic liver mass on conventional B-mode ultrasound. Clinical differentiation of mass-like FFC and liver mass is important due to different clinical interventions. Contrast-enhanced imaging (CEI) or biopsy is reliable for this differentiation, but is expensive and invasive. This study aimed to explore utilities of ultrasound elastography for this differentiation. This study enrolled 79 patients with focal liver lesions (FLLs), of which 26 were mass-like FFC confirmed by at least 2 CEI modalities. The other 53 were liver masses, confirmed by pathology (n = 28) or at least 2 CEI modalities (n = 25). Lesion stiffness value (SV), absolute stiffness difference (ASD), and stiffness ratio (SR) of lesion to background were obtained using point shear-wave elastography (pSWE) and compared between FFC group and liver mass group. The performance of SV, ASD, and SR for identifying FFC from liver mass was evaluated. SV was 5.6 ± 2.4 versus 16 ± 12 kPa, ASD was 2.0 ± 1.9 versus 11 ± 12 kPa, and SR was 1.4 ± 0.6 versus 3.0 ± 1.9 for FFC and liver mass group, respectively (P < .0001). The area under the receiver operating characteristic curve of SV, ASD, and SR for discriminating mass-like FFC and liver mass was 0.840, 0.842, and 0.791, respectively (P < .05). Particularly, with cut-off ASD < 1.0 kPa, positive predictive value was 100%, specificity was 100%, and accuracy was 82% for diagnosing FFC. pSWE may be a potential useful modality for identifying mass-like FFC from liver mass, which might help reduce the necessity for further CEI or biopsy for diagnosing mass-like FFC.

Assessment of liver fibrosis by ultrasound elastography and contrast-enhanced ultrasound: a randomized prospective animal study

This study aimed to assess liver fibrosis by contrast-enhanced ultrasound (CEUS) and point shear-wave elastography (pSWE) in rabbits and compare the performance of the two techniques. Eighty rabbits were divided into experimental (n=60) and control group (n=20). In the experimental group, liver fibrosis (F1–F4) was induced by subcutaneous injection of carbon tetrachloride. CEUS and pSWE of the liver was performed for the two groups at a 4-week interval for 40 weeks. The portal vein rise time (PV-RT), time to peak (PV-TTP), mean transit time (PV-MTT) and the maximum signal intensity (PV-Imax) were analyzed with time-intensity curves (TICs). Liver stiffness value (LSV) was obtained through pSWE. Histologic examination of liver specimens of the rabbits was performed to evaluate the fibrosis stage. PV-RT, PV-TTP, PV-Imax and LSV were significantly different among five liver fibrosis stages (F0–F4) (P<0.01). PV-Imax and LSV displayed better diagnostic performance than PV-RT, PV-TTP, PV-MTT. For diagnosing≥F1 stage fibrosis, the area under the receiver operating characteristic curve (AUROC) of PV-Imax was 0.870, which was similar to that of LSV 0.874 (P=0.94). For diagnosing ≥F2, ≥F3 and ≥F4 stage fibrosis, the AUROC of PV-Imax and LSV was 0.845 vs. 0.956 (P=0.04), 0.789 vs. 0.954 (P=0.01) and 0.707 vs. 0.933 (P=0.03). Both CEUS and pSWE had the potential to be complementary imaging tools in the evaluation of liver fibrosis. The performance of pSWE may be better than CEUS.