Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Evaluation of the Therapeutic Effect of Contrast-Enhanced Ultrasound on Different Types of Knee Osteoarthritis in the Elderly

Objective: To evaluate the curative effect of the Traditional Chinese Medicine (TCM) external therapy on knee osteoarthritis patients with different TCM constitutions using musculoskeletal ultrasonography and contrast-enhanced ultrasonography, and to explore the application value of contrast-enhanced ultrasonography in knee joint diseases. Methods: A total of 57 patients diagnosed with knee osteoarthritis in Shaanxi University of Traditional Chinese Medicine from December 2019 to May 2021 were collected, and they were divided into qi stagnation and blood stasis type group (23 cases) and cold-dampness obstruction type group (34 cases) according to the traditional Chinese medicine method. All patients were given acupuncture combined with TCM fumigation and washing. All patients underwent musculoskeletal ultrasonography and contrast-enhanced ultrasonography before and after treatment, observed and recorded relevant data, and compared the treatment effects between the two groups. Results: 85.96% (49/57) of knee osteoarthritis (KOA) patients had suprapatellar bursa effusion, 42.1% (24/57) had iliotibial band bursae effusion, some of which had poor sound transmission, and thickened synovium was seen in most effusions, 33.33% (19/57) had osteophyte formation. Compared with before treatment, the depth of suprapatellar sac effusion in the Qi stagnation and blood stasis type group decreased after treatment (P Conclusion: Musculoskeletal contrast-enhanced ultrasonography was used to quantitatively evaluate the efficacy of TCM external therapy on KOA for different TCM constitutions. Dynamic observation of synovial lesions of knee osteoarthritis provides a valuable imaging method for evaluating the efficacy of traditional Chinese medicine.

value of contrast-enhanced ultrasound in the differential diagnosis of gallbladder lesion

AIM To describe contrast-enhanced ultrasound(CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as(1) benign,(2) probably benign,(3) probably malignant or(4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared.RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS(e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8%and 95.2%, respectively. These were significantly higher than conventional ultrasound(82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer.CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound.

Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma

AIM: To analyze contrast-enhanced ultrasound(CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma(HEHE) in comparison to other multilocular benign focal liver lesions(FLL).METHODS: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus.RESULTS: HEHE manifested as a single(n = 3) or multinodular(n = 22) FLL. On CEUS, HEHE showed rim-like(18/25, 72%) or heterogeneous hyperenhancement(7/25, 28%) in the arterial phase and hypoenhancement(25/25, 100%) in the portal venous and late phases(PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas(18/25, 72%); in seven patients(7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature(P < 0.01).CONCLUSION: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.

Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

Objective: To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS). Methods: ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively. Imaging features of conventional ultrasound and CEUS were analyzed. The parameters of time intensity curve (TIC), including the arrival time, peak intensity (PI) in the lesions, the starting time for washout, and the intensity difference at 3 min (Delta I-3) after contrast agent infection between the lesion and the liver parenchyma, were compared between ICC and hepatic inflammatory lesions. Results: Twenty-five ICC and fifteen inflammatory patients were included in this study. Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound. Using CEUS, three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC; two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis. Washout started at 34.5 +/- 3.5 s and 61.5 +/- 12.9 s for ICC and inflammatory lesions respectively (P < 0.001). The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8 +/- 3.1 dB in ICC and 4.2 +/- 2.3 dB in inflammatory group (P < 0.001). The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-off value of the intensity difference was 7.7 dB. Conclusions: Combined with TIC analysis, and particularly with the characteristic of the early-starting and obvious washout in ICC, CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

Liver metastases:Contrast-enhanced ultrasound compared with computed tomography and magnetic resonance

The development of ultrasound contrast agents with excellent tolerance and safety profiles has notably improved liver evaluation with ultrasound(US)for several applications,especially for the detection of metastases.In particular,contrast enhanced ultrasonography(CEUS)allows the display of the parenchymal microvasculature,enabling the study and visualization of the enhancement patterns of liver lesions in real time and in a continuous manner in all vascular phases,which is similar to contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging.Clinical studies have reported that the use of a contrast agent enables the visualization of more metastases with significantly improved sensitivity and specificity compared to baseline-US.Furthermore,studies have shown that CEUS yields sensitivities comparable to CT.In this review,we describe the state of the art of CEUS for detecting colorectal liver metastases,the imaging features,the literature reports of metastases in CEUS as well as its technique,its clinical role and its potential applications.Additionally,the updated international consensus panel guidelines are reported in this review with the inherent limitations of this technique and best practice experiences.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma

BACKGROUND：Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection.It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations.The study aimed to illustrate characteristics of contrast-enhanced ultrasound（CEUS）and its diagnostic value in gallbladder adenoma.METHODS： Thirty-seven patients with 39 gallbladder adenoma- toid lesions （maximal diameter _〉10 mm and without metastasis） were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individuaUy among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS： Adenoma lesions showed iso-echogenicity in ul- trasound, and an eccentric enhancement pattern, ＂fast-in and synchronous-out＂ contrast enhancement pattern and homo- geneous at peak-time enhancement in CEUS. The homogenic- ity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion （100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively）. The characteristic of the eccentric enhance- ment pattern had the highest diagnostic ability in differenti- ating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively.CONCLUSIONS： CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps （〉_10 mm in diameter）. Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Contrast-enhanced ultrasound imaging for intestinal lymphoma

BACKGROUND Intestinal lymphoma is a rare tumor.Contrast-enhanced ultrasound(CEUS)findings of intestinal lymphoma have not been reported previously,and the relationship between CEUS and clinicopathological features and prognostic factors is still unknown.AIM To describe the B-mode US and CEUS features of intestinal lymphoma and investigate the correlation of CEUS and histopathological features.METHODS This was a single-center retrospective study.Eighteen patients with histologically confirmed intestinal lymphoma underwent B-mode US and CEUS examinations between October 2016 and November 2019.We summarized the features of Bmode US and CUES imaging of intestinal lymphoma and compared the frequency of tumor necrosis in intestinal lymphomas with reference to different pathological subtypes(aggressive or indolent)and clinical stage(early or advanced).The time–intensity curve parameters of CEUS were also compared between patients with normal and elevated serum lactate dehydrogenase.RESULTS In B-mode imaging,four patterns were observed in intestinal lymphoma:Mass type(12/18,66.7%),infiltration type(1/18,5.6%),mesentery type(4/18,22.2%)and mixed type(1/18,5.6%).All cases were hypoechoic and no cystic areas were detected.On CEUS,most cases(17/18,94.4%)showed arterial hyperechoic enhancement.All cases showed arterial enhancement followed by venous wash out.A relatively high rate of tumor necrosis(11/18,61.1%)was observed in this study.Tumor necrosis on CEUS was more frequent in aggressive subtypes(10/13,76.9%)than in indolent subtypes(1/5,20.0%)(P=0.047).There were no correlations between tumor necrosis and lesion size and Ann Arbor stage.There was no significant difference in time–intensity curve parameters between normal and elevated lactate dehydrogenase groups.CONCLUSION B-mode US and CEUS findings of intestinal lymphoma are characteristic.We observed a high rate of tumor necrosis,which appeared more frequently in aggressive pathological subtypes of intestinal lymphoma.

Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.

Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer

瞄准：作为基于微容器的灌注特征把发炎区分开来与胰腺的癌的一个方法评估提高对比的 endosonography。方法：在有怀疑的慢性胰炎的 86 个病人(变老：62+/-12 年；性别：f/m 38/48 ) ，胰腺的损害被常规内视镜的 B 模式，力量 Doppler 超声和提高对比的力量模式检验(日立 EUB 525， SonoVue， 2.4 mL， Bracco ) 用为恶意的损害的下列标准：用常规力量 Doppler 的没有可检测的 vascularisation 在用 SonoVue 提高对比的技术和没有可检测的静脉的容器里面的短距离上的动脉的容器的扫描、不规则的外观损害。如果所有标准是可检测的，恶意的损害被假定[内视镜的超声(EUS ) 指导了的标准答案好针渴望细胞学，操作] 。没有瘤形成的慢性胰炎的标准在 SonoVue 的注射前被定义为没有可检测的 vascularisation，在在 SonoVue 的注射和动脉、静脉的容器的察觉以后的至少 20 公里的距离上的容器的常规外观。结果：常规 EUS 的敏感和特性为胰腺的癌症分别地是 73.2% 和 83.3% 。与恶意的胰腺的损害和特性在 56 个病人中的 51 个增加到 91.1% 的提高对比的 EUS 的敏感与长期的煽动性的胰腺的疾病在 30 个病人中的 28 个增加了到 93.3% 。结论：提高对比的内视镜的超声改进在慢性胰炎和胰腺的癌之间的区别。

Management of hepatocellular carcinoma: The role of contrast-enhanced ultrasound

Hepatocellular carcinoma(HCC)is the sixth most common neoplasm and the third cause of cancer death worldwide.Contrast enhanced ultrasound(CEUS)has been applied for more than ten years and plays increasingly important roles in the management of HCC.On the basis of the Guideline and Good Clinical Practice Recommendations for CEUS in the liver-update 2012and related literature about the management of HCC,we summarize the main roles and applications of CEUS in the management of HCC,including HCC surveillance,diagnosis,CEUS-guided treatment,treatment response evaluation and follow-up.The diagnostic algorithm for HCC is also suggested.Meanwhile,the comparisons between CEUS and contrast enhanced computed tomography/magnetic resonance imaging(CECT/CEMRI)in these areas are made.Although CEUS is subject to the same limitation as ordinary US and is inferior to CECT/CEMRI in some aspects,CEUS has proved to be of great value in the management of HCC with inher-ent advantages,such as sufficient high safety profile making it suitable for patients with renal failure or allergic to iodine,absence of radiation,easy reproducibility and high temporal resolution.The tremendous application of CEUS to the diagnosis and treatment of HCC provides more opportunities for patients with HCC diagnosed at different stages.

Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound

BACKGROUNI）： Hepatocellular adenoma （HCA） is a rare benign tumor of the liver. It is of clinical importance to dif- ferentiate HCA from other liver tumors, especially hepatocel- lular carcinoma （HCC）. This study aimed to evaluate the char- acteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound （CEUS） findings. METHODS： Twenty-six patients （10 males and 16 females; mean age 36.2＋5.0 years） with 26 histopathologically proven HCAs were retrospectively identified. According to the maxi- mum diameter of HCAs, they were divided into three groups： 〈30 mm, 30-50 mm, and 〉50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit （Philips Bothell, WA, USA）. For each lesion, a dose of 2.4 mL SonoVue~ （Bracco Imaging Spa, Milan, Italy） was injected as a quick bolus into the cubital vein. Lesions＇ echogenicity, color-Doppler flow imaging and contrast en- hancement patterns were recorded. RESULTS： Grayscale ultrasound revealed that most of HCAs were hypoechoic （73.1%, 19/26）. Spotty calcifications were detected in 26.9% （7/26） of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% （12/26） of the HCAs. CEUS showed that 73.1% （19/26） of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% （14/26） showed decreased contrast enhancement in the late phase. There was no significant difference in enhance- ment patterns among different sizes of HCAs （P〉0.05）. Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs.

Application of contrast-enhanced ultrasound after livertransplantation:Current status and perspectives

Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents(UCAs), in combination with contrastspecific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and posttransplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrastenhanced ultrasound applications in liver transplantation.

Role of contrast-enhanced ultrasound in follow-up assessment after ablation for hepatocellular carcinoma

AIM:To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).METHODS:A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT).The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d.Both im-ages of follow-up CEUS and CECT were reviewed by radiologists.The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTPfree.LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule.The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci.On CEUS and CECT,LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e.,hyper-enhancing during the arterial phase and washout in the late phase).With CECT as the reference standard,the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.RESULTS:During a follow-up period of 1-31 mo (median,4 mo),169 paired CEUS and CECT examinations were carried out for the 141 patients.For a total of 221 ablated lesions,266 comparisons between CEUS and CECT findings were performed.Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT,there was significant difference (P < 0.001).In comparison with CECT,the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13,respectively;the sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%,97.4%,81.8%,94.4% and 92.3%,respectively.Meanwhile,131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT,there was also significant difference (P < 0.05).In comparison with CECT,the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65,respectively;the sensitivity,specificity,PPV,NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%,92.0%,92.4%,76.7% and 84.0%,respectively.CONCLUSION:The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparisonwith CECT.

Contrast-enhanced 3D ultrasound in the radiofrequency ablation of liver tumors

Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world.Radiofrequency ablation(RFA) is a well recognized,effective and minimally invasive means of treating malignant hepatic tumors.This article describes the use of contrast-enhanced 3D ultrasound(CE-3DUS) in the staging,targeting and follow-up of patients with liver tumors undergoing RFA.In particular,its value in the management of large hepatic lesions will be illustrated.Current limitations of CE-3DUS and future developments in the technique will also be discussed.In summary,CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence,in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.

Contrast-enhanced ultrasound in diagnosis and characterization of focal hepatic lesions

The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases,has led to an important increase in identification of focal liver lesions.The development of contrastenhanced ultrasound(CEUS) opens a new window in the diagnosis and follow-up of these lesions.This technique offers obvious advantages over the computed tomography and magnetic resonance,without a decrease in its sensitivity and specificity.The new second generation contrast agents,due to their intravascular distribution,allow a continuous evaluation of the enhancement pattern,which is crucial in characterization of liver lesions.The dual blood supply in the liver shows three different phases,namely arterial,portal and late phases.The enhancement during portal and late phases can give important information about the lesion's behavior.Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis.The role of emerging techniques as a contrastenhanced three-dimensional US is also discussed.In this article,the advantages,indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed.

Contrast-enhanced ultrasound:Improving the preoperative staging of hepatocellular carcinoma and guiding individual treatment

AIM:To investigate the clinical role of contrast-enhanced ultrasound(CEUS) combined with contrast-enhanced computed tomography(CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma(HCC) and guide surgical decisionmaking.METHODS:Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study.CEUS and CE-CT/MRI were performed before surgery.Intraoperative ultrasound(IOUS)wascarried out after liver mobilization.Lesions depicted by each imaging modality were counted and mapped.To investigate the impact of tumor size on the study,we divided the patients into two groups,the"Smaller group"(S-group,≤5 cm in diameter)and the"Largergroup"(L-group,>5 cm in diameter).The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CE-CT/MRI,CEUS,IOUS,CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared.Changes in the surgical strategy as a result of CEUS and IOUS were analyzed.RESULTS:One hundred and twenty-seven nodules,comprising 94 HCCs confirmed by histopathology and33 benign lesions confirmed by histopathology and follow-up,were identified in 69 patients.The overall diagnostic sensitivity rates of CE-CT/MRI,CEUS,IOUS and CEUS+CE-CT/MRI were 78.7%,89.4%,89.4%and 89.4%,respectively.There was a significant difference between CEUS+CE-CT/MRI and CE-CT/MRI(P=0.046).Combining CEUS with CT or MRI increased,the diagnostic specificity compared with CT/MRI,CEUS and IOUS,and this difference was statistically significant(100%,72.7%,97.0%,and 69.7%,P=0.004,P=0.002,P=0.002,respectively).The diagnostic accuracy was significantly higher for CEUS+CT/MRI compared with CT/MRI(92.1%vs 77.2%,P=0.001).The TNM staging of tumors based on CEUS+CE-CT/MRI approximated to the final pathological TNM staging(P=0.977).There was a significant difference in the accuracy of TNM staging when comparing CEUS+CECT/MRI with CE-CT/MRI(P=0.002).Before surgery,strategies were changed in 15.9%(11/69)of patients as a result of CEUS.Finally,only 5.7%(4/69)of surgical strategies were changed because of IOUS findings.In the S-group,CEUS revealed 12 false positive lesions,including seven false positive lesions that were diagnosedby preoperative imaging examinations and five by IOUS.In contrast,in the L-group,IUOS revealed eight new malignant lesions;six of these lesions were true HCCs that were also identified by preoperative CEUS.CONCLUSION:CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC.CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.

Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases

AIM:To assess if software assisted-contrast-enhanced ultrasonography (CEUS) provides reproducible perfusion parameters of hepatic parenchyma in patients affected by chronic liver disease. METHODS:Forty patients with chronic viral liver disease, with (n = 20) or without (n = 20) cirrhosis, and 10 healthy subjects underwent CEUS and video recordings of each examination were then analysed with Esaote's Qontrast software. CEUS dedicated software Qontrast was used to determine peak (the maximum signal intensity), time to peak (TTP), region of blood value (RBV) proportional to the area under the time-intensity curve, mean transit time (MTT) measured in seconds and region of blood flow (RBF). RESULTS:Qontrast-assisted CEUS parameters displayed high inter-observer reproducibility (k coefficients of 0.87 for MTT and 0.90 TTP). When the region of interest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients (vs non-cirrhotics and healthy subjects) (71.0 ± 11.3 s vs 82.4 ± 15.6 s, 86.3 ± 20.3 s, P < 0.05). MTTs in the patients with liver cirrhosis were significantly shorter than those of controls (111.9 ± 22.0 s vs 139.4 ± 39.8 s, P < 0.05), but there was no significant difference between the cirrhotic and non-cirrhotic groups (111.9 ± 22.0 s vs 110.3 ± 14.6 s). Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls (23.9 ± 5.9 vs 18.9 ± 7.1, P = 0.05). There were no significant intergroup differences in the RBVs and RBFs. CONCLUSION:Qontrast-assisted CEUS revealed reproducible differences in liver perfusion parameters during the development of hepatic fibrogenesis.

Contrast-enhanced ultrasound of the pancreas

The introduction of contrast-enhanced ultrasonography(CEUS) has led to major improvements in the diagnostic capabilities of ultrasound(US).The innovative use of CEUS for study of the pancreas has created the need for a definition of the most frequent dynamic features of solid and cystic masses.CEUS is less expensive compared to computed tomography and magnetic resonance imaging and is able to significantly improve the accuracy of US,allowing better characterization and staging of pancreatic pathologies.