Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading

Objective

The quantitative parameters in the contrast-enhanced ultrasonography time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their possible implication for histological grading of HCC.

Methods

A total of 130 HCC patients (115 males and 15 females; age: 48.13±11.00 years) were studied using contrast-enhanced ultrasonography time–intensity curve and histological pathology. The quantification software Sonoliver® (TomTec Imaging Systems, Unterschleissheim, Germany) was applied to derive time–intensity curves of regions of interest in the interior of HCCs and in reference. Quantitative parameters of 115 patients were successfully obtained, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), rise slope (RS) and washout time (WT). Histological grading of HCC was performed using haematoxylin–eosin staining, and monoclonal antibodies specific for smooth muscle actin were used to observe unpaired arteries (UAs).

Results

There were significant differences among WTs in the three differentiated HCC groups (p<0.05). However, there were no significant differences among RT, TTP, RS and IMAX in the differentiated HCC groups. Moreover, the number of UAs in the differentiated HCC groups showed no statistical significance.

Conclusion

WT plays an important role in predicting well, moderately and poorly differentiated HCC.The majority of hepatocellular carcinomas (HCCs) develop through multistep hepatocarcinogenesis 1]. Various types of hepatocellular nodules are seen in cirrhotic livers. The International Working Party of the World Congress of Gastroenterology classifies hepatocellular nodules into six types: regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, well-differentiated HCC, moderately differentiated HCC and poorly differentiated HCC. The histopathological grades and types constitute well-established prognostic factors 2]. Thus, early diagnosis and confirmation of the type of hepatocellular nodules present and cellular differentiation before treatment are important.Although definite differentiation among HCC by imaging is usually impossible, the relationship between tumour cellular differentiation and image findings has been studied using contrast-enhanced (CE) CT, CEMRI and CE ultrasonography (CEUS). Tumour pathological differentiation correlates well with image findings ,3?8].Dynamic CEUS during the past decade has noticeably improved the detection and characterisation of focal liver lesions 9]. A previous study showed that CEUS and spiral CT provided a similar diagnostic accuracy in the characterisation of focal liver lesion 10]. The appearance of HCC on CEUS has also been described well. Current low-mechanical-index techniques for CEUS using second-generation microbubble agents have advantages in characterising HCC, including real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules. Some studies postulated that variations of enhancement patterns may be related to the pathological function of HCC ,5?8]. Moderately differentiated HCCs generally show classic enhancement features, with presence of hypervascularity in the arterial phase and washout during the portal phase, whereas well and poorly differentiated tumours account for most atypical variations in the arterial phase and portal venous phase 7].Reports assessing hepatocellular nodules have been based on visual analysis, despite the disadvantages of interobserver variability and low reproducibility of results. Although quantitative analysis CEUS perfusion provides more objective, reliable and reproducible results 11], the time–intensity curve (TIC) of CEUS has been obtained by quantification software for offline analysis ,12?14], from which a series of semi-quantitative perfusion parameters is extracted and analysed. An analysis of the parameters of TIC in HCC has proven the correlation of CEUS with unpaired arteries (UAs) in HCC 14]. In the present study, we compare the quantitative parameters in CEUS and UAs in different pathological gradings of HCCs to explore their possible implication for histological grading of HCC.