Contrast-enhanced ultrasound: The evolving applications

Contrast-enhanced ultrasound (CEUS) is a major breakthrough for ultrasound imaging in recent years. By using a microbubble contrast agent and contrast-specific imaging software, CEUS is able to depict the micro- and macro-circulation of the targeted organ, which in turn leads to improved performance in diagnosis. Due to the special dual blood supply system in the liver, CEUS is particularly suitable for liver imaging. It is evident that CEUS facilitates improvement for characterization of focal liver lesions (FLLs), detection of liver malignancy, guidance for interventional procedures, and evaluation of treatment response after local therapies. CEUS has been demonstrated to be equal to contrast-enhanced computed tomography or magnetic resonance imaging for the characterization of FLLs. In addition, the applicability of CEUS has expanded to non-liver structures such as gallbladder, bile duct, pancreas, kidney, spleen, breast, thyroid, and prostate. The usefulness of CEUS in these applications is confirmed by extensive literature production. Novel applications include detecting bleeding sites and hematomas in patients with abdominal trauma, guiding percutaneous injection therapy and therefore achieving the goal of using interventional ultrasonography in managing splenic trauma, assessing the activity of Crohn's disease, and detecting suspected endoleaks after endovascular abdominal aneurysm repair. Contrast-enhanced intraoperative ultrasound (US) and intracavitary use of CEUS have been developed and clinically studied. The potential use of CEUS involves sentinel lymph node detection, drug or gene delivery, and molecular imaging. In conclusion, the advent of CEUS has greatly enhanced the usefulness of US and even changed the status of US in clinical practice. The application of CEUS in the clinic is continuously evolving and it is expected that its use will be expanded further in the future.     

Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

Objective

To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT).

Methods

Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated.

Results

In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125).

Conclusion

The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.     

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 contrast-enhanced 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 contrast-enhanced 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.     

Focal liver lesions: role of contrast-enhanced ultrasound

The introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new possibilities in liver imaging. Initially, only intermittent imaging with Doppler detection was available. Second-generation contrast agents and low mechanical index real-time scanning techniques are decisive advances that enable convenient liver examinations with high sensitivity and specificity. Hepatic lesions usually show typical perfusion and enhancement patterns through the various contrast phases, which help their characterization. Several published studies and the daily clinical routine show that, as opposed to conventional ultrasound (US), contrast-enhanced US can substantially improve detection and differentiation of focal liver lesions. Today, contrast-enhanced US is the dynamic imaging modality of choice for differentiation of focal liver lesions. Contrast uptake patterns of the most relevant liver lesions, as well as important clinical indications are presented and discussed.     

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.     

Differentiating benign from malignant solid breast lesions: Combined utility of conventional ultrasound and contrast-enhanced ultrasound in comparison with magnetic resonance imaging

Objective

To prospectively evaluate the diagnostic efficacy of conventional ultrasound (US), contrast-enhanced US (CEUS), the combined use of two modalities, and magnetic resonance imaging (MRI) in the differentiation of focal solid breast lesions.

Materials and methods

61 patients with BI-RADS category 3–5 breast lesions detected at conventional US underwent CEUS and MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of conventional US, CEUS, combination of two modalities and MRI for discrimination between benign and malignant breast lesions.

Results

Tissue specimens of 61 breast lesions were obtained either from surgical resection (n = 46) or from needle biopsy (n = 15). Histopathologic diagnosis revealed 28 benign and 33 malignant lesions. The diagnostic performance of conventional US and CEUS in differentiating benign from malignant breast lesions showed no significant difference (P = 0.741). The combination of two modalities significantly improved the diagnostic accuracy compared with either conventional US or CEUS alone (P = 0.031 and P = 0.012, respectively). The area under the ROC curve (A_z) value for the combined use of two modalities for discrimination between benign and malignant breast lesions was 0.94, and that for MRI was 0.91, whereas no statistical difference was found between them (P = 0.296).

Conclusion

The combined use of conventional US and CEUS has a better diagnostic performance than either method alone and displays good agreement with MRI in the differentiation capability for benign and malignant breast lesions.     

Discrepancy of contrast-enhanced ultrasonographic pattern with two contrast agents in steatohepatitic subtype hepatocellular carcinoma: A case report

Contrast-enhanced ultrasound (CEUS) is one of the important imaging modalities for diagnosis of hepatocellular carcinoma (HCC). Sonovue and Sonazoid are the third-generation of ultrasound contrast agents that have been commercialized and widely used in clinical applications. This study introduces the imaging differences between these two agents in vascular phases for the first time. A 54-year-old man clinical suspected liver cancer. He had chronic hepatitis B for more than 20 years. The result of alpha-fetoprotein was 36.45μg/L (normal< 20μg/L). The imaging pattern of CEUS with Sonovue was “fast-in and fast-out” performance, while the pattern of “fast-out” was absent after portal phase with Sonazoid, even in Kupffer phase. The lesion was diagnosed as lipid-rich HCC by contrast-enhanced MRI. After liver resection, pathology revealed that it was hepatocellular carcinoma contained poor-differentiated steatohepatitis subtype and moderate-differentiated microtrabecular subtype. The imaging difference mainly existed in the part of steatohepatitis subtype. Steatohepatitis subtype HCC can be showed as “fast-in and no wash-out” characteristic in Sonazoid CEUS. Though the mechanism remains not fully clarified, this different enhancing pattern may provide a potential for the supplement of the guidelines and differential of steatohepatitis subtype HCC.     

Contrast-enhanced ultrasound is helpful in the differentiation of malignant and benign breast lesions

Objective

To evaluate the significance of contrast-enhanced ultrasound (CEUS) examination in differential diagnosis of malignant and benign breast lesions.

Methods

Seventy-one patients with seventy-six breast tumors are selected randomly. CEUS examinations were performed before and after bolus injection of the contrast agent SonoVue (Bracco, Milan, Italy). Specific sonographic quantification software, Qontrast, was adopted to determine the morphology of vessels. Wash-in and wash-out parameters of each lesion were assessed for both procedures.

Results

The final histopathological findings distinguished 45 malignant and 31 benign from all of the lesions. Following SonoVue administration different perfusion phases could be identified: early (0-1 min), mid (1-4 min) and late (4-6 min) phases. In the early phase, CEUS identified 91.1% of malignant tumors characterized by a claw-shaped enhancement, while 83.9% of benign tumors had a homogeneous enhancement, with a statistically significant difference between the two enhancement patterns (χ² = 43.16, P < 0.01). Moreover, contrast medium persistence in the late phase was helpful in the identification of benign and malignant tumors (χ² = 46.88, P < 0.01): contrast medium was present in 88.9% of malignant tumors, while in only 9.7% of the benign tumors. The study showed that various parametric imaging color maps for peak intensity and time to peak were mostly suggestive of malignancy, while quite uniform peak intensity and time to peak of color maps were the characteristic of benign tumors. The study also found that malignant lesions presented with a higher maximum intensity signal than benign ones (P < 0.05) on the time-intensity curves.

Conclusions

CEUS cooperating with conventional US shows improved accuracy in differentiating between malignant and benign breast tumors. It could be a reliable diagnostic method of breast lesions.     

Role for contrast-enhanced ultrasound in assessing complications after kidney transplant

Kidney transplantation (KT) is an effective treatment for end-stage renal disease. Despite their rate has reduced over time, post-transplant complications still represent a major clinical problem because of the associated risk of graft failure and loss. Thus, post-KT complications should be diagnosed and treated promptly. Imaging plays a pivotal role in this setting. Grayscale ultrasound (US) with color Doppler analysis is the first-line imaging modality for assessing complications, although many findings lack specificity. When performed by experienced operators, contrast-enhanced US (CEUS) has been advocated as a safe and fast tool to improve the accuracy of US. Also, when performing CEUS there is potentially no need for further imaging, such as contrast-enhanced computed tomography or magnetic resonance imaging, which are often contraindicated in recipients with impaired renal function. This technique is also portable to patients’ bedside, thus having the potential of maximizing the cost-effectiveness of the whole diagnostic process. Finally, the use of blood-pool contrast agents allows translating information on graft microvasculature into time-intensity curves, and in turn quantitative perfusion indexes. Quantitative analysis is under evaluation as a tool to diagnose rejection or other causes of graft dysfunction. In this paper, we review and illustrate the indications to CEUS in the post-KT setting, as well as the main CEUS findings that can help establishing the diagnosis and planning the most adequate treatment.     

超声造影对移植肝脏局灶性病变的诊断价值

目的：评价超声造影对移植肝脏局灶性病变的诊断价值。方法：对30例移植肝脏局灶性病变患者,用西门子Sequoia 512彩色多普勒超声诊断仪和超声对比剂Sonovue进行超声造影检查,观察三个时相的对比剂灌注模式,并用自动跟踪对比量化技术（Axius ACQ）对病灶及周围肝组织进行定量分析。所有病例均经病理及临床随访证实。结果：30例移植肝脏局灶性病变患者,超声造影正确诊断29例,包括肝癌复发18例、非均质脂肪肝5例、肝血管瘤4例、梗死灶2例;超声造影误诊1例,超声造影怀疑肝癌复发,经穿刺活检诊断为局灶性脂肪浸润。结论：移植肝脏局灶性病变具有各自典型的增强模式,超声造影技术有助于移植肝脏局灶性病变的鉴别诊断,具有重要临床价值。     

Management of hepatocellular carcinoma: The role of contrast-enhanced Tultrasound简

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 2012 and 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 inherent 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.     

Diameter of the common bile duct in the elderly patient: measurement by ultrasound

We wanted to assess the width of the common bile duct (CBD) in an asymptomatic elderly (> 75 years) population, since no previous report has particularly considered the important age-related increase in CBD diameter for this patient group. CBD width of 92 asymptomatic people over 75 years of age (mean 84.7 years, range 75–96 years) without clinical or laboratory evidence for biliary, hepatocellular or pancreatic disease was measured by real-time high-resolution ultrasound of the upper abdomen. All examinations were performed by one experienced radiologist. Mean values were calculated for three groups: patients with and without cholecystolithiasis and after cholecystectomy. Statistical analysis was carried out by analysis of variance. Considering the measurements of all patients, the mean width (± SD) of the CBD was calculated as 6.5 ± 2.5 mm. The difference between patients without cholecystolithiasis (6.2 ± 2.3 mm) and patients after cholecystectomy (8.7 ± 2.9 mm) was statistically significant (P < 0.0001). Cholecystolithiasis (6.0 ± 1.6 mm) proves not to be an additional factor for CBD widening in comparison with patients without stone disease. The CBD of these very elderly subjects shows a considerable increase in comparison with the recommended borderline values in the ultrasound literature. An upper limit of 10 mm seems reasonable for patients with and without cholecystolithiasis. A significant increase in CBD width after cholecystectomy was found and measurements up to 14 mm may occur. Measurements have to be correlated with clinical and laboratory findings. Received 1 December 1997; Revision received 27 February 1998; Accepted 3 March 1998     

超声造影剂量对肾恶性肿瘤时间-强度曲线参数影响

目的探讨超声造影剂量对肾恶性肿瘤造影时间-强度曲线参数的影响。方法将31例肾恶性肿瘤患者按剂量1.2、1.5、2.0、2.4 ml分为4组进行超声造影检查,应用时间-强度曲线获得4组定量参数,包括始增时间、达峰时间、峰值强度、曲线上升支斜率、曲线上升支下面积,分析4组参数与造影剂剂量的关系。结果始增时间、达峰时间均随剂量增加而缩短,2.4 ml组与其他3组间差异有统计学意义(P<0.05);峰值强度随造影剂量增加而增强,2.4 ml组与1.2 ml组、1.5ml组差异均有统计学意义(P<0.05);曲线上升支斜率、曲线上升支下面积在4组间差异无统计学意义(P>0.05)。结论一定范围内造影剂量对时间-强度曲线参数影响不显著,但增至2.4 ml时差异较显著。     

Contrast-enhanced ultrasound imaging of the vasa vasorum of carotid artery plaque

The vasa vasorum of carotid artery plaque is a novel marker of accurately evaluating the vulnerability of carotid artery plaque, which was associated with symptomatic cerebrovascular and cardiovascular disease. The presence of ultrasound contrast agents in carotid artery plaque represents the presence of the vasa vasorum in carotid artery plaque because the ultrasound contrast agents are strict intravascular tracers. Therefore, contrast-enhanced ultrasound (CEUS) is a novel and safe imaging modality for evaluating the vasa vasorum in carotid artery plaque. However, there are some issues that needs to be assessed to embody fully the clinical utility of the vasa vasorum in carotid artery plaque with CEUS.     

肝门部恶性胆道梗阻的MRC和PTC的对照研究

目的 :探讨MRC与PTC在肝门部恶性胆道梗阻中的临床应用价值。方法 :搜集经手术、病理或影像学证实并同时行MRC和PTC的肝门部恶性胆道梗阻患者 16例 ,其中 ,胆管癌 9例 ,转移癌 4例 (结肠癌 2例 ,胆囊癌 1例 ,胃癌 1例 ) ,肝门部肝癌 3例。分别在MRC和PTC图像上测量梗阻远端扩张的左、右肝管的宽径、狭窄段长度 ,计算并判断是否完全梗阻及其正确率。统计学处理采用配对t检验和 χ2 检验。结果 :MRC和PTC在显示扩张的左右肝管上无差异(t =1.2 7,P >0 .2及t=1.3 3 ,P >0 .2 ) ,MRC评价胆管狭窄长度和PTC相比有显著性差异 (t =3 .3 1,P <0 .0 1)。MRC判断狭窄程度的准确性明显低于PTC( χ2 =8.5 0 ,P <0 .0 0 5 )。结论 :MRC可很好的显示肝内胆管扩张程度 ,判断狭窄部位。但对狭窄程度的评估存在夸大效应。PTC不仅可评价肝内胆管扩张情况 ,并能准确测量狭窄段长度 ,判断狭窄部位是否完全梗阻。     

超声新技术在妇产科的应用

近年来,超声技术发展迅速,三维超声成像、超声对比剂及扩展成像都是目前超声研究和应用领域的热点。本文综述三项新技术的基本原理及其在妇产科的应用和发展前景。     

Contrast-enhanced ultrasound study of primary hepatic angiosarcoma: a pitfall of non-enhancement

Objective

To investigate the contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA).

Methods

The sonographic findings and CEUS images of PHA in three patients were retrospectively analyzed.

Results

In our study, 3 cases of PHA (2 multiple nodules and 1 solitary mass) showed similar enhancement pattern on CEUS, characterized by remarkable central non-enhancement and peripheral irregular enhancement in the arterial and portal phase, and complete wash-out in the late phase. Furthermore, we unexpectedly found that abundant neoplastic tissues were present in the central area of non-enhancement on pathological evaluation. Based on literature review, we supposed that the unusual finding may be associated with the very low velocity of blood flow in the central region of tumors.

Conclusion

CEUS could well depict PHA with some common features, which may provide valuable clues in diagnosis of this rare disease. And non-necrotic tumor tissue of PHA could also demonstrate non-enhancement on CEUS, which warrant further investigations.     

Intra-biliary contrast-enhanced ultrasound for evaluating biliary obstruction during percutaneous transhepatic biliary drainage: A preliminary study

Objectives

The aimed of this study was to investigate the value of intra-biliary contrast-enhanced ultrasound (IB-CEUS) for evaluating biliary obstruction during percutaneous transhepatic biliary drainage (PTBD).

Materials and methods

80 patients with obstructive jaundice who underwent IB-CEUS during PTBD were enrolled. The diluted ultrasound contrast agent was injected via the drainage catheter to perform IB-CEUS. Both conventional ultrasound and IB-CEUS were used to detect the tips of the drainage catheters and to compare the detection rates of the tips. The obstructive level and degree of biliary tract were evaluated by IB-CEUS. Fluoroscopic cholangiography (FC) and computer tomography cholangiography (CTC) were taken as standard reference for comparison.

Results

Conventional ultrasound displayed only 43 tips (43/80, 53.8%) of the drainage catheters within the bile ducts while IB-CEUS identified all 80 tips (80/80, 100%) of the drainage catheters including 4 of them out of the bile duct (P < 0.001). IB-CEUS made correct diagnosis in 44 patients with intrahepatic and 36 patients with extrahepatic biliary obstructions. IB-CEUS accurately demonstrated complete obstruction in 56 patients and incomplete obstruction in 21 patients. There were 3 patients with incomplete obstruction misdiagnosed to be complete obstruction by IB-CEUS. The diagnostic accuracy of biliary obstruction degree was 96.3% (77/80).

Conclusion

IB-CEUS could improve the visualization of the drainage catheters and evaluate the biliary obstructive level and degree during PTBD. IB-CEUS may be the potential substitute to FC in the PTBD procedure.     

Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma

The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.     

实时超声造影技术诊断肝脏微小局灶性病变的价值

目的:探讨肝脏微小局灶性病变(最大径≤2cm)的实时超声造影诊断价值。材料和方法:对205个≤2cm肝脏局灶性病变分别进行实时超声造影及常规超声检查,将诊断结果分为良性、恶性和不能确定,最终诊断经病理学、同期其他影像及实验室检查证实,并随访10~30个月。结果:恶性肿瘤65个病灶,良性病灶140个。与病理诊断比较,超声造影诊断的敏感性、特异性及准确性分别为85.0%、90.5%及88.5%,常规超声分别为40.0%、47.6%及42.6%。病灶动脉期高增强及门静脉期或延迟期低增强为诊断恶性的重要指标。结论:实时超声造影技术对鉴别诊断肝脏微小(≤2cm)局灶性病变具有重要的临床应用价值。