Diagnosis of liver cirrhosis with contrast-enhanced ultrasound

The assessment of the extent of liver fibrosis is very important for the prognosis and clinical management of chronic liver diseases. Although liver biopsy is the gold standard for the assessment of liver fibrosis, new non-invasive diagnostic methods are urgently needed in clinical work due to certain limitations and complications of biopsy. Noninvasive imaging studies play an important role in the diagnosis of focal liver disease and diffuse liver diseases. Among them, ultrasonography is the first choice for study of the liver in clinical work. With the development of ultrasound contrast agents and contrast specific imaging techniques, contrast-enhanced ultrasound (CEUS) shows good performance and great potential in the evaluation of liver fibrosis. Researchers have tried different kinds of contrast agent and imaging method, such as arrival time of contrast agent in the hepatic vein, and quantitative analysis of the enhancement level of liver parenchyma, to evaluate the degree of liver fibrosis during the past 10 years. This review mainly summarizes the clinical studies concerning the assessment of liver fibrosis using CEUS.     

Focal liver lesions in cirrhosis: Role of contrast-enhanced ultrasonography

Contrast-enhanced ultrasound (CEUS) represents a great innovation for the evaluation of focal liver lesions (FLLs). The main advantage of CEUS is the real-time imaging examination and the very low toxicity in patients with renal failure. Liver cirrhosis has been recognized as a major risk factor for the onset of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). HCC in liver cirrhosis develops as the last step of a complex that leads to the gradual transformation from regenerative nodule through dysplastic nodule to HCC. In patients with liver cirrhosis, a surveillance program is recommended consisting of ultrasound (US) for detecting small focal lesions. A wide spectrum of benign and malignant lesions other than HCC may be found in the cirrhotic liver and their differentiation is important to avoid errors in staging diseases that may preclude potentially curative therapies. Several published studies have explored the value of CEUS in liver cirrhosis and they have been shown to have excellent diagnostic and prognostic performances for the evaluation of non-invasive and efficient diagnosis of FLLs in patients at high risk for liver malignancies. The purpose of this article is to describe and discuss CEUS imaging findings of FLLs including HCC and ICC, all of which occur in cirrhotic livers with varying prevalence.     

Detection and characterization of focal liver lesions with contrast-enhanced ultrasonography in patients with hepatitis C-induced liver cirrhosis

Background: Hepatitis C virus (HCV)-associated liver cirrhosis provides a major preneoplastic condition for hepatocellular carcinoma (HCC). Ultrasonography (US) is usually used for screening of HCC, but needs improvement.

Purpose: To assess whether use of a second-generation ultrasound contrast agent can improve characterization of focal liver lesions and detection of HCC in HCV-infected patients with liver cirrhosis.

Material and Methods: In total, 96 US studies in 49 HCV-infected patients with liver cirrhosis were performed. The patients were first examined with a baseline US. After this, a diagnostic decision was made and recorded. The patients were then re-examined with contrast-enhanced ultrasound (CEUS), and the diagnostic triage was repeated. The patients were followed up for at least 1 year.

Results: On baseline US, indeterminate focal lesions were found in 27 examinations. After CEUS, a confident diagnosis of HCC was made in eight of these examinations. In an additional eight US examinations, diagnosis of regenerative/dysplastic noduli was established. In one patient with no detectable focal lesion at baseline examination, an indeterminate malignant lesion was detected with CEUS. This lesion was further investigated with computed tomography and diagnosed as HCC.

Conclusion: Our study indicates that the use of CEUS significantly improves diagnostic confidence. CEUS improves the detection of HCC in patients with HCV-induced liver cirrhosis. Also, CEUS makes it possible to rule out malignancy in many cases where baseline US shows indeterminate focal lesions. In low-endemic countries, the use of CEUS in screening for HCC may be considered.     

超声造影对肝脏局灶性病变的定量分析及临床价值研究

目的 探讨超声造影对肝脏局灶性病变的定量分析结果及临床价值.方法 选取2017年1月～2019年1月100例肝脏病变患者,根据病变性质分为恶性组(n=67)和良性组(n=33).分别进行实时超声造影及彩色多普勒超声检查.应用时间-强度曲线(TIC曲线)分析超声造影图像.结合TIC曲线形态及由TIC曲线得到的病灶的始增时...     

灰阶超声造影在肝脏局灶性病变诊断中的应用

目的探讨实时灰阶超声造影在肝脏局灶性病变诊断与鉴别诊断中的应用价值。方法回顾性分析36例肝脏局灶性病变患者的超声造影表现,评价病灶增强时相及其形态学特征,并进行血流动力学分析。同时与CDFI进行比较,部分病例与CT进行对照。结果不同性质占位性病变具有不同的造影增强表现;与CDFI相比,超声造影可明显提高病灶血流显示率;同时,对于直径≤1.0cm病灶,检出率明显提高。结论超声造影在肝脏局灶性病变诊断和鉴别诊断中具有重要意义。     

Diagnosis of portal vein thrombosis discontinued with liver tumors in patients with liver cirrhosis and tumors by contrast-enhanced US: A pilot study

Aims

We assessed the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant portal vein thrombosis (PVT) in patients who had liver tumors.

Methods

Seventeen consecutive patients who had cirrhosis, liver tumors, and PVT were prospectively studied with CEUS. CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent (SonoVue, Bracco, Milan, Italy). Presence or absence of thrombus enhancement on CEUS were considered diagnostic for malignant or benign PVT. Five patients also underwent percutaneous portal vein fine-needle biopsy under US guidance. All patients were followed-up. Shrinkage of the thrombus and/or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis, whereas the enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered consistent with malignancy.

Results

Follow-up showed signs of malignant thrombosis in 14 of 17 patients. CEUS showed early arterial enhancement of the PVT in 14 patients of 14 malignant PVT, 1 patient of 3 benign PVT and the absence of thrombus enhancement in 2 patients of 3 benign PVT. FNB confirmed the results for malignant PVT in four of five patients, for benign granulomatous inflammation PVT in one of five patients in which CEUS showed early arterial enhancement of the PVT. The sensitivity, specificity and accuracy is 100%, 66.7% and 93.3% at diagnosis of malignant PVT using CEUS. In one patient with intrahepatic bile duct stone, CEUS were positive for malignant PVT, whereas FNB was negative (benign granulomatous inflammation PVT); follow-up examination confirmed benign PVT.

Conclusion

CEUS seems to be the pretty sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis and tumors.     

超声造影对肝脏转移癌的诊断应用价值

目的:探讨超声造影对肝脏转移癌的诊断应用价值.方法:对49例恶性肿瘤患者肝脏行常规超声检查及低机械指数超声造影检查,对肝内转移性病灶超声造影表现进行分析.结果:经超声造影新发现47个病灶,其中小于1.0cm的病灶占55.3%(26/47).肝转移病灶的增强模式可分为4种:A.病灶周边快速环状强化60/131(45.8%),病灶内部呈低或无增强,之后周边增强部分造影剂迅速退出呈低增强;B.病灶于动脉期呈快速整体强化并迅速廓清51/131(38.9%);C.病灶于动脉期和门脉期基本与肝脏实质同步强化,延迟晚期呈低增强12/131(9.2%);D.病灶于造影三期均低于肝实质呈低增强表现8/119(6.1%).结论:肝脏转移病灶来源和大小不同其增强模式表现亦不相同;实时超声造影可提高对肝脏转移病灶尤其可提高直径小于1.0cm的微小转移灶的检出率.     

Evaluation of renal urothelial carcinoma by contrast-enhanced ultrasonography

Purpose

To observe ultrasonographic features of urothelial carcinoma in renal pelvis and evaluate contrast-enhanced ultrasound (CEUS) in diagnosis.

Materials and methods

Fifty-two patients with urothelial carcinoma underwent preoperative conventional US, colour Doppler flow imaging (CDFI) and CEUS.

Results

Of 52 total lesions, 41 (78.8%) could be clearly identified by US, and 49 (94.2%) were enhanced by CEUS. Among US-imaged lesions, 39 (95.1%) were solid tumours, and two (4.9%) were mixed solid-cystic; 25 (61.0%) were isoechoic, 11 (26.8%) hypoechoic, and five (12.2%) hyperechoic. Analysis of tumour blood flow by CDFI characterised 17 avascular lesions (41.5% of total), 16 hypovascular (39.0%), and 8 hypervascular (19.5%). The resistance index ranged from 0.65 to 0.88 (mean of 0.71). Enhancement was seen in 49 lesions after injection of SonoVue. A slow enhancement pattern was observed in 36 lesions (73.5%) relative to renal cortex, and 13/49 (26.5%) showed simultaneous enhancement. At peak enhancement, 38 lesions (77.6%) were hypo-enhanced, six (12.2%) iso-enhanced, and five (10.2%) hyper-enhanced. There were 12 lesions with intertumoural necrosis or haemorrhage (24.5%) that were heterogeneously enhanced, and 37 (75.5%) were homogeneously enhanced. A fast washout pattern was observed in 46 lesions (93.9%), synchronous washout in two (4.08%), and slow washout in one (2.04%).

Conclusions

Slow-in, fast-out, and hypo-enhancement properties are associated with renal urothelial carcinoma and may thus have diagnostic value. We found that CEUS is able to identify tumours that are ambiguous by conventional US, and it thus significantly improves the confidence of diagnosis.     

超声造影与增强CT对肾癌的诊断分析

目的:本研究旨在比较超声造影(CEUS)和增强CT(CECT)在肾癌病灶中的诊断价值,探讨超声造影在肾癌的诊断价值。方法:对54例患者临床诊断为肾脏内占位性病灶进行CEUS和CECT检查,通过分析病灶CEUS和CECT的特点,比较两种方法的诊断效能。结果:54个病灶中34个为肾脏恶性肿瘤,20个为肾脏良性病灶,CEUS和CECT诊断敏感性、特异性、准确性、阳性预测值、阴性预测值分别为97.05%、85.0%、92.59%、91.67%、94.44%与91.18%、80.00%、87.04%、88.57%、84.21%。两种方法诊断差异无统计学意义(P>0.05)。结论:分析比较CEUS和CECT在诊断肾癌过程中,两种方法诊断效能无明显差异,均能为临床诊断提供重要依据,但CEUS对微循环灌注方面及假包膜的观察优于CECT;CEUS定量评价肾肿瘤血管现处于动物实验阶段,临床上特异指标的找寻仍有待于进一步研究。     

超声造影及增强CT诊断肾脏外伤的对比研究

目的评价超声造影(contrast-enhanced ultrasonography,CEUS)与增强CT在肾脏外伤诊断中的应用价值。方法 57例肾脏外伤患者分别进行超声造影与增强CT检查,根据美国创伤外科协会(AAST)肾外伤分级标准及肾外伤CT分级判断外伤程度,并对结果进行对照研究。结果超声造影发现1例I级肾外伤,而增强CT未发现;CEUS漏诊2例I级肾外伤;1例CEUS将Ⅲ级高估为Ⅳ级;2例将Ⅳ级低估为Ⅲ级。增强CT与CEUS各自的诊断符合率分别为98.2%、91.2%,两者诊断结果具有较好的一致性(P=0.000)。结论 :CEUS在评价实质器官外伤上具有优势,而增强CT在判断腹部合并伤方面更具优势,两种检查技术的有机组合必将大大提高诊断准确率。     

Diagnosis of liver cirrhosis with US: receiver-operating characteristic analysis of multidimensional caudate lobe indexes

To assess the utility of changes in the volume of the caudate lobe in the sonographic diagnosis of liver cirrhosis, the authors studied 58 patients with histologically proved cirrhosis, 18 patients with fatty liver, 28 patients with liver metastases, seven patients with lymphomatous liver involvement, and 75 healthy individuals. The longitudinal (CL), transverse (CT), and anteroposterior (CAP) diameters of the caudate lobe and the transverse diameter of the right lobe (RL) were measured, and one-, two-, and three-dimensional caudate lobe indexes and ratios were calculated. The analysis of the diagnostic performance of these criteria, compared by means of receiver-operating characteristic curves, revealed that the ratio of the three-dimensional caudate index (CI3) to the right lobe diameter (CI3/RL = [CL X CT X CAP]/RL) was superior to all other calculated criteria. At a specificity of 95%, the sensitivity of CI3/RL was 94.7%, compared with 73.3% for CT/RL. No significant differences were found between the control group and patients with fatty liver, metastases, or lymphomatous involvement. The study suggests that CI3/RL is the most reliable quantitative criterion for the US diagnosis of liver cirrhosis.     

超声造影与CT增强扫描对肝占位性病变的诊断价值比较

目的 :对比超声造影与CT增强扫描在肝占位性病变中的诊断价值,为临床诊断肝占位性病变提供参考依据。方法 :回顾性分析71例肝占位性病变患者的临床资料,比较超声造影与CT增强扫描的诊断阳性率,对比2种检查方法的诊断价值。结果:超声造影对肝癌、肝血管瘤及肝局灶性结节增生的诊断阳性率分别为83.33%、88.00%及82.14%,而CT增强扫描分别为88.89%、92.00%及85.71%,2种检查方法的诊断阳性率比较差异无统计学意义(P0.05)。此外,2种检查方法对肝癌、肝血管瘤及肝局灶性结节增生均具有较高的诊断效能(P0.05)。结论:超声造影与CT增强扫描对肝占位性病变的诊断价值相当。     

肝硬化结节与微小肝癌的彩超诊断与鉴别

目的:探讨联合应用二维超声、彩色多普勒、频谱多普勒、彩色能量多普勒等多种超声检查技术对肝硬化结节与微小肝癌的早期诊断与鉴别的临床意义。方法:对696例结节性肝硬化病人的临床检查中小于2 cm的异常回声结节进行进一步检查,筛选出微小肝癌结节,并与肝硬化结节鉴别。结果:肝硬化结节有细小而规则的结节及粗大的不规则的结节,而周边呈网格状增高回声,回声可较细而整齐,围绕不规则低回声区,境界清晰、中间类似正常肝组织回声,并有小血管的结构可见,周边无血流信号,无彩色多普勒能量成像;微小肝癌直径小于2 cm,癌结节的数目少,多为单发,76.5%呈低回声,病灶多为圆形或类圆形,边缘整齐,境界清楚,回声均匀,癌结节周边伴有声晕或后方伴增强效应,82.4%癌结节周边可见彩色血流环绕,内部见条状、树枝状、网篮状等彩色血流信号[5.4]。癌结节内血流呈高阻力动脉血流为主,88.2%的癌结节可出现彩色多普勒能量成像。结论:微小肝癌的早期诊断是早期治疗和改善预后的首要条件。联合应用多种超声技术可提高对微小肝癌的检出。超声检查无创伤、无痛苦、简便、可重复,目前已成为肝癌筛选检查的首选方法。     

Diagnosis of pancreatic tumors by endoscopic ultrasonography

Pancreatic tumors are highly diverse, as they can be solid or cystic, and benign or malignant. Since their imaging features overlap considerably, it is often difficult to characterize these tumors. In addition, small pancreatic tumors, especially those less than 2 cm in diameter, are difficult to detect and diagnose. For characterizing pancreatic tumors and detecting small pancreatic tumors, endoscopic ultrasonography (EUS) is the most sensitive of the imaging procedures currently available. This technique also provides good results in terms of the preoperative staging of pancreatic tumors. EUS-guided fine needle aspiration (EUS-FNA) has also proved to be a safe and useful method for tissue sampling of pancreatic tumors. Despite these advantages, however, it is still difficult to differentiate between benign and malignant, solid or cystic pancreatic tumors, malignant neoplasms, and chronic pancreatitis using EUS, even when EUS-FNA is performed. Recently, contrast-enhanced EUS with Doppler mode (CE-EUS) employing ultrasound contrast agents, which indicate vascularization in pancreatic lesions, has been found to be useful in the differential diagnosis of pancreatic tumors, especially small pancreatic tumors. However, Doppler ultrasonography with contrast-enhancement has several limitations, including blooming artifacts, poor spatial resolution, and low sensitivity to slow flow. Consequently, an echoendoscope was developed recently that has a broad-band transducer and an imaging mode that was designed specifically for contrast-enhanced harmonic EUS (CEH-EUS) with a second-generation ultrasound contrast agent. The CEH-EUS technique is expected to improve the differential diagnosis of pancreatic disease in the future. This review describes the EUS appearances of common solid and cystic pancreatic masses, the diagnostic accuracy of EUS-FNA, and the relative efficacies and advantages of CE-EUS and CEH-EUS along with their relative advantages and their complementary roles in clinical practice.     

Unidentified liver metastases at ultrasonography or computed tomography

Sixty-six patients with hepatic metastases, examined by ultrasonography (US) and computed tomography (CT) with an interval of a few days between the two examinations, showed discrepancies between the US and CT findings. The US and CT images were compared lesion by lesion, and the reasons why a metastasis was missed at US or CT were analysed. Lesions larger than 3 cm in diameter could be detected at technically successful examinations with both methods. The unreliable imaging regions with US were the ventrocranial aspect of the right lobe, the caudate lobe, and in obese patients the dorsal part of the right lobe. With CT, the caudal aspect of the left lobe, the area surrounding the gallbladder, and portions beneath the ribs were most unreliably imaged. Sometimes, at either US or CT, the image characteristics of the metastasis were too similar to those of the normal parenchyma to be differentiated.     

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma

Objective:

To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC).

Methods:

34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.

Results:

The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively.

Conclusion:

The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS.

Advances in knowledge:

Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.Dynamic contrast-enhanced ultrasonography (CEUS) has noticeably improved the detection and characterisation of focal liver lesions during the past decade [1]. The enhancement patterns of the lesion are evaluated in three vascular phases (the hepatic arterial, portal venous and late phases), where the hepatic arterial phase provides information on the degree and pattern of vascularity and the portal venous and late phases provide important information on the differention between benign and malignant liver lesions [1]. A previous study has shown that CEUS using SonoVue® (Bracco, Milan, Italy) and spiral-CT provides similar diagnostic accuracy in the characterisation of focal liver lesions [2].The typical enhancement of focal nodular hyperplasia (FNH) on CEUS showed hyperenhancement in the three vascular phases with a stellate vascular and centrifugal enhancement in the arterial phase or a hypoenhancing central scar in the late phase [1, 3–5]. However, these features have not been observed in all cases of FNH, particularly in small lesions. A study on FNH showed that 3 out of 13 lesions (23.1%) were hypoenhancing in the late phase [6] and 3 out of 10 lesions <3 cm had spoke-wheel patterns and 2 had central scars [4]. There is also a broad variation of stellate vascular enhancement in FNHs with a range from 27.3% to 73.3% and of central scar with a range from 36.4% to 63.3% [3–5]. Thus, it can be difficult to differentiate atypical FNHs from other hypervascular malignant tumours, such as hepatocellular carcinoma (HCC), and hypervascular metastases [3]. Furthermore, a hypoenhancing central scar has been described in fibrolamellar HCC and sclerosing or scirrhous HCC [7, 8], and a central feeding artery with spoke-wheel sign has also been described in two scirrhous HCCs [8]. Hence, a comprehensive approache rather than simply estimating the haemodynamics could be beneficial for differential diagnosis.The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which time–intensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9–11]. This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9]. In the present study, CEUS was applied to evaluate enhancing patterns of FNH and HCC; quantitative features of CEUS in the two groups were generated with the analytic software Sonoliver® (TomTec Imaging Systems, Germany) and compared to explore their potential in the differential diagnosis. Furthermore, the quantitative analysis of CEUS was used to characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.     

Role of ultrasonography and contrast-enhanced ultrasonography in a case of Krukenberg tumor

We report a case of Krukenberg tumor of gastric origin with adnexal metastasis,in which ultrasonography(US) and contrast-enhanced US(CEUS) played a key diagnostic role.An 64-year-old female patient was referred to our department for abdominal pain,nausea and ascites.US examination was performed as first line diagnostic imaging approach,confirming the presence of ascites and detecting marked thickness of the gastric wall and a right adnexal mass.CEUS was immediately performed and showed arterial enhancement followed by wash-out in the venous phase of both the gastric wall and the adnexal mass,suggesting the diagnosis of gastric cancer with right adnexal metastasis(Krukenberg syndrome).The patient underwent USguided paracentesis and esophagogastroduodenoscopy that showed linitis plastica.Cytologic examination of the peritoneal fluid revealed the presence of signetring cells,and histologic examination of the specimen obtained by endoscopic biopsy showed primary gastric mucus-producing adenocarcinoma with signetring cells.Although transvaginal US is undoubtedly the method of choice to evaluate ovarian tumors,abdominal US and CEUS can provide key diagnostic elements,supporting clinicians in the first steps of the diagnostic work-up of abdominal and pelvic masses.     

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence

Aim: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. Materials and methods: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. Results: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P<0.01) while did not differ from CT (89%, 89%, 0.945, respectively; P>0.05). Conclusion: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.