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.     

Kontrastverst?rkte Ultraschallbildgebung der A.?carotis

A conventional grey scale, Doppler sonography and color-coded Doppler ultrasound examination should be the first step in the diagnosis of the vessels supplying the brain and have a major impact in diagnostic imaging. This ultrasound examination allows the simultaneous acquisition of morphologic and hemodynamic information with high spatial and temporal resolution. Most of the pathological changes of the extracranial arteries can thus be reliably detected. Contrast-enhanced ultrasound (CEUS) is a promising new non-invasive method for the diagnosis and follow-up of complex carotid abnormalities. In addition to improving current carotid structural scans, CEUS has the potential to improve or provide additional information on carotid arterial diseases, such as the reliable differentiation between internal carotid artery (ICA) occlusion and pseudo-occlusion, improved visualization of in-stent stenosis, extracranial ICA aneurysms and carotid dissection.In this article the contribution of color-coded duplex ultrasound and CEUS in assessing various pathologies of the carotid artery will be addressed.     

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.     

Contrast-enhanced ultrasonography in the follow-up of patients with hepatic metastases from breast carcinoma

PURPOSE: Oncological treatment planning relies on the evaluation of treatment response, which is defined by the change in size of measurable lesions. The purpose of this study was to evaluate the use of contrast-enhanced ultrasound (CEUS) to obtain a precise measurement of hepatic metastases in breast cancer patients with fatty-liver disease. MATERIALS AND METHODS: Twelve consecutive patients with 25 liver metastases from breast cancer and fatty liver disease, as defined by US criteria, were enrolled in this prospective study. All patients underwent conventional US, CEUS and multidetector computed tomography (MDCT), used as the gold standard for measuring the maximum diameter of lesions. Agreement between US, CEUS and MDCT measurements was analysed using Altman-Bland plots; 95% confidence limits were calculated for the difference among means. RESULTS: Mean diameter as measured by MDCT was 26.2 mm (range 11-83). US allowed measurement of 20/25 lesions. In 15 lesions, CEUS measurements were more accurate than those obtained by US. The difference among means was 1.1 mm with a 95% confidence interval (-9.2, 11.4) for US measurements and 0.6 mm with a 95% confidence interval (-2.0, 3.1) for CEUS. CONCLUSIONS: Our preliminary data show that CEUS can be used to obtain more accurate measurements than conventional US for the follow-up of patients with metastases in fatty liver.     

Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

Objective

To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions.

Method

Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT.

Results

(1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05).

Conclusion

CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the diagnostic consistency among doctors. The performances of CEUS are similar to that of CECT in the diagnosis of pancreatic carcinoma and focal pancreatitis.     

超声造影结合超声引导下穿刺活检对结直肠癌肝转移的诊断价值

目的：评价超声造影（ CEUS）结合超声引导下穿刺活检（ IU）对结直肠癌肝转移的诊断价值。方法总结经手术病理证实的结直肠癌病例21例,共切除病灶21个。后经3～25个月,其他影像学检查（ CT、MRI）发现肝内可疑转移病灶33个,（1个病灶11例,2个病灶8例,3个病灶2例）。经超声造影检查明确肝内转移病灶是否存在,经超声引导下对可疑病灶进行穿刺活检,设定CEUS为A组,IU为B组,后经手术病理结果对照。结果A、B两组与AorB组组间比较t检验,A组与B组之间无统计学差异,A、B两组分别与A orB组有统计学差异, P＜0.05。结论 CEUS结合IU可提高恶性病灶检出率。     

Liver haemangioma: common and uncommon findings and how to improve the differential diagnosis

Haemangiomas are common focal liver lesions, generally detected in the work-up of asymptomatic patients. From the pathological point of view, they can be classified as small (capillary) or large, with cavernous vascular spaces that may show thrombosis, calcifications and hyalinisation. The polymorphic imaging appearance of haemangiomas depends on their histological features and flow pattern. The widespread use of cross-sectional imaging has allowed an increased detection rate and a better characterisation of this benign tumour. Recent developments of ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) providing high spatial and temporal resolution, together with the use of new contrast agents and/or pulse sequences has broadened the spectrum of imaging findings, contributing to diagnostic refinement in difficult cases. The scope of the present article is to provide an overview of the range of appearances of haemangiomas, explored with recent cross-sectional imaging modalities, emphasising its atypical findings as explored by temporally resolved contrast-enhanced imaging.     

The value of contrast enhanced ultrasonography in detection of liver metastases from colorectal cancer: a prospective double-blinded study

OBJECTIVE: To compare sensitivity and specificity of contrast enhanced ultrasonography (CEUS) with conventional ultrasonography (US) in detection of liver metastases in patients with colorectal adenocarcinoma (CRC) in a patient-by-patient analysis. MATERIALS AND METHODS: A prospective study of 461 consecutive patients referred to the Department of Colorectal Surgery, Aarhus University Hospital with primary or local recurrence of CRC. In order to detect possible liver metastases all patients underwent liver US, followed by CEUS by another investigator. Multislice CT scanning (MDCT), and intraoperative ultrasonography (IOUS) were then performed. Fine-needle biopsy was performed on all suspicious lesions. Each examination was interpreted blindly and the combination of biphasic MDCT, IOUS, follow up and biopsy was the gold standard. RESULTS: Standard of reference found liver metastases in 54 patients (14.8%). Contrast enhanced ultrasonography improved the sensitivity significantly in detection of liver metastases from 0.69 by US to 0.80 (p=0.031). In 24 patients, CEUS found a higher number of metastases than US (p<0.001). The specificity (0.98) and the positive predictive value (0.86) was the same. CONCLUSION: Contrast enhanced ultrasonography improves sensitivity in detection of liver metastases in patients with CRC and in nearly half of the cases CEUS found a higher number of metastases than US.     

Contrast enhanced ultrasound in the detection of liver metastases: a prospective multi-centre dose testing study using a perfluorobutane microbubble contrast agent (NC100100)

Objective

To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy.

Methods

157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 μL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the “Standard Of Reference” (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test.

Results

165 metastases were present in 92 patients who each had 1–7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p?=?0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p?Conclusion The diagnostic performance of CEUS is dose dependent with the 0.12 μL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases.     

Focal liver lesions in cirrhosis: value of contrast-enhanced ultrasonography compared with Doppler ultrasound and α-fetoprotein levels

Purpose

This study aimed to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in characterising focal liver lesions in cirrhosis and to validate its use in lesions discovered during surveillance for hepatocellular carcinoma (HCC).

Materials and methods

Between 2003 and 2006, 128 cirrhotic patients with focal liver lesions at baseline ultrasonography (US) were studied by power colour Doppler US (Doppler US) and CEUS. Serum alpha-fetoprotein (AFP) levels were assessed in all patients. Fine-needle biopsy or other reference modalities such as computed tomography (CT), magnetic resonance imaging (MRI) or digital subtraction angiography (DSA) were used as the gold standard. The accuracy of baseline US, Doppler US, AFP levels, combined US and AFP levels and combined US, Doppler US and CEUS in characterising focal liver lesions was assessed. Diagnostic performance was compared using the McNemar test.

Results

A total of 207 focal liver lesions (101 benign and 106 malignant) were identified in 128 patients. CEUS sensitivity and specificity for lesion characterisation were 96.2% and 97.0%, respectively, whereas its positive and negative predictive values were 97.1% and 96.1%. CEUS accuracy was 96.6%, higher than that of US (72.0%), Doppler US (70.0%), AFP levels (65.7%), combined US and Doppler US (70.0%) and combined US and AFP levels (90.3%). The differences between US and CEUS were statistically significant (p<0.05).

Conclusions

CEUS can characterise focal liver lesions with 96.6% accuracy, a value higher than US, Doppler US, AFP levels, combined US and AFP levels and combined US and Doppler US. CEUS should therefore be used to characterise focal liver lesions detected during HCC surveillance of cirrhotic patients.     

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.     

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.     

Focal liver lesions: can SonoVue-enhanced ultrasound be used to differentiate malignant from benign lesions?

OBJECTIVE: To evaluate whether contrast-enhanced ultrasound (CEUS) with SonoVue could differentiate malignant focal liver lesions (FLLs) from benign lesions and provide lesion type diagnoses. MATERIALS AND METHODS: Four hundred fifty-six patients with 554 FLLs were examined by CEUS with SonoVue using low mechanical index, nonlinear imaging techniques. Each lesion was characterized by 2 independent off-site readers as malignant or benign and given specific lesion type diagnosis, if possible, both at baseline ultrasound (US) and after SonoVue administration (CEUS). The final diagnosis was achieved by histopathology obtained from biopsy or surgical specimens, or by typical manifestation on contrast-enhanced CT or MRI. RESULTS: The diagnostic accuracies of the 2 readers were 41.9% and 35.2% for baseline US, which improved significantly to 87.2% and 87.9% for CEUS (P < 0.05). Interreader agreement also increased with CEUS compared with baseline US (ê value changed from 0.49 to 0.77). The accuracy for lesion type diagnosis was 38.4% and 32.5% for baseline US, which increased to 77.6% and 78.0% for CEUS (P < 0.05). CONCLUSIONS: CEUS with SonoVue improves differentiation between malignant and benign FLLs, and also provides improved lesion type (differential) diagnosis.     

Characterization of hypoechoic focal hepatic lesions in patients with fatty liver: diagnostic performance and confidence of contrast-enhanced ultrasound

The objective of this study was to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) to characterize hypoechoic focal hepatic lesions (HFHL) in fatty liver (FL). A study group of 105 patients with FL and 105 HFHLs (52 malignant and 53 benign) underwent CEUS after SonoVue administration. Two blinded readers independently reviewed baseline ultrasound (US) and CEUS scans and classified each lesion as malignant or benign on a five-point scale of confidence, and recorded whether further imaging work-up was needed. Sensitivity, specificity, areas under the receiver operating characteristic (ROC) curve (A (z)), and interobserver agreement were calculated. We observed that the diagnostic confidence improved after reviewing CEUS scans for both readers (A (z)=0.706 and 0.999 and A (z)=0.665 and 0.990 at baseline US and CEUS, respectively; p<0.0001). Inter-reader agreement increased (weighted k=0.748 at baseline US vs. 0.882 at CEUS). For both readers, after CEUS, the occurrence of correctly characterized lesions increased (from 27/105 [27.5%] to 94/105 [89.5%], and from 19/105 [18.1%] to 93/105 [88.6%], respectively; p<0.0001) and the need for further imaging decreased (from 93/105 [88.6%] to 26/105 [24.8%], and from 96/105 [91.4%] to 40/105 [38.1%], respectively; p<0.0001). We conclude that CEUS improves the diagnostic performance of radiologists in the characterization of HFHLs in FL and reduces the need for further imaging work-up.     

Characterization of focal liver lesions: comparative study of contrast-enhanced ultrasound versus spiral computed tomography

The purpose of this study was to compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with spiral computed tomography (SCT) for the characterization of focal liver lesions (FLL) and to determine the degree of correlation between the two techniques. Seventy-seven FLL (45 hepatocellular carcinomas; 12 metastases; ten hemangiomas; two regenerating/dysplastic nodules; eight focal nodular hyperplasias) detected with ultrasound (US) were prospectively evaluated by CEUS using a second-generation contrast agent and SCT (with an interval of no more than one month between the two techniques). Independent observers made the most probable diagnosis and the results were compared with the final diagnoses (histology n = 59; MRI n = 18). Statistical analysis was performed by the Chi-square and Kappa tests. CEUS provided a correct, specific diagnosis in 69/77 (90%) of the FLL, while SCT did so in 67/77 (87%). The sensitivity, specificity, and diagnostic accuracy for malignancy were 91%, 90%, and 91%, respectively, for CEUS and 88%, 89%, and 88%, respectively, for SCT. No statistically significant difference was found between CEUS and SCT in the characterization of FLL (p > 0.05). In addition, agreement between the two imaging techniques was good (k = 0.75). We conclude that CEUS and SCT provide a similar diagnostic accuracy in the characterization of FLL, with a good degree of correlation between the two techniques.     

Unenhanced and Contrast-Enhanced Ultrasonography During Hepatic Transarterial Embolization and Chemoembolization With Drug-Eluting Beads

The purpose of this study was to describe and evaluate the findings of unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) when these modalities are applied during transarterial embolization (TAE) or transarterial chemoembolization (TACE) of liver tumors. Sixteen tumors (9 hepatocellular carcinomas, 5 metastases from colorectal cancer, and 2 hemangiomas) were treated with TAE with microspheres and/or TACE with drug-eluting beads. All of these lesions were studied with intraprocedural unenhanced US and 12 were studied with intraprocedural CEUS. For the latter, a second-generation echo-enhancer (SonoVue; Bracco, Milan, Italy) and a low mechanical index technique were used. Intraprocedural findings were classified according to an arbitrary scale and were compared with pretreatment imaging (CEUS and computed tomography or CEUS and magnetic resonance imaging), with postembolization angiography, and with follow-up results. On unenhanced intraprocedural US, 13 of 16 tumors demonstrated intralesional high-level echoes of varying extent. These feature correlated poorly (r = 0.33, p = 0.097) with and generally underestimated the actual extent of necrosis. Exceptionally, high-level echoes that occupied the largest part of the treated lesions were associated with >50% tumor necrosis. Intraprocedural CEUS clearly depicted immediate partial or complete disappearance of tumor enhancement as a result of TAE/TACE. Three of 6 tumors with complete devascularization on postembolization angiogram showed residual enhancement on intraprocedural CEUS. Intraprocedural CEUS findings correlated closely (r = 0.91, p = 0.002) with follow-up findings. Intraprocedural sonography, particularly with echo-enhancers, could be used for intraprocedural monitoring in selected cases of liver tumors that undergo TAE or TACE.     

The “humble” bubble: Contrast-enhanced ultrasound

The use of contrast-enhanced ultrasound (CEUS) is increasing within the field of medical imaging. Ultrasonic contrast agent (UCA) contain gas microbubbles similar in size to red corpuscles which provide highly reflective interfaces, enabling dynamic demonstration of echogenic streams of the contrast within the anatomical area of interest on real-time grey scale ultrasound. Longevity of the microbubbles has been improved by changing their composition. The application of CEUS in the UK continues to grow, bringing it into territories historically occupied by computerised tomography (CT) scanning and magnetic resonance imaging (MRI). Hence, the role of CEUS may be of interest to all diagnostic imaging practitioners. Here we summarise the mode of action and use of CEUS, and its role within a range of applications. The potential risks of CEUS are compared to other contrast-enhanced imaging techniques. The benefits of CEUS and its implications for diagnostic imaging practice are also covered.     

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.     

Sichere Diagnostik zystischer Nierenläsionen

Clinical/methodical issue

Cystic renal lesions are commonly seen during routine ultrasound examinations of the abdomen.

Standard radiological methods

Some cystic renal lesions cannot be sufficiently characterized using native ultrasound. In these cases additional imaging might be necessary.

Methodical innovations

Contrast-enhanced ultrasound (CEUS) is a reliable imaging modality to characterize cystic renal lesions. Contrast enhancement of septations and the cystic wall are visualized in high resolution. This information helps to categorize the cystic renal lesions applying the CEUS Bosniak classification. This classification helps to estimate the probability of a malignant etiology of cystic renal lesions.

Performance

Using CEUS, cystic renal lesions can be characterized with a high sensitivity and specificity.

Achievements

The advantages of CEUS include that there is no effect on the function of the kidneys or the thyroid gland and no radiation exposure. In some cases, additional cross-sectional imaging is necessary to optimize diagnostic accuracy.

Practical recommendations

CEUS is a helpful imaging modality to characterize cystic renal lesions, to avoid unnecessary follow-ups and to detect malignant cystic renal lesions.