Hepatocellular cancer response to radiofrequency tumor ablation: contrast-enhanced ultrasound

Radiofrequency ablation (RFA) is increasingly being used as percutaneous treatment of choice for patients with early stage hepatocellular carcinoma (HCC). An accurate assessment of the RFA therapeutic response is of crucial importance, considering that a complete tumor ablation significantly increases patient survival, whereas residual unablated tumor calls for additional treatment. Imaging modalities play a pivotal role in accomplishing this task, but ultrasound (US) is not considered a reliable modality for the evaluation of the real extent of necrosis, even when color/power Doppler techniques are used. Recently, newer microbubble-based US contrast agents used in combination with grey-scale US techniques, which are very sensitive to non-linear behavior of microbubbles, have been introduced. These features have opened new prospects in liver ultrasound and may have a great impact on daily practice, including cost-effective assessment of therapeutic response of percutaneous ablative therapies. Technical evolution of CEUS focusing on findings after RFA are illustrated. These latter are detailed, cross-referenced with the literature and discussed on the basis of our personal experience. Timing of CEUS posttreatment assessment among with advantages and limitations of CEUS are also described with a perspective on further technologic refinement.     

Active abdominal bleeding: contrast-enhanced sonography

Active contrast medium extravasation is a recognized and important angiographic and computed tomographic (CT) sign of bleeding. It is an indicator of active, ongoing, and potentially life-threatening hemorrhage and, hence, of the need for an immediate surgical or interventional treatment. Sonography (US) is frequently used as the first imaging option for screening patients with traumatic and nontraumatic abdominal emergencies. Owing to the current possibilities of low-mechanical index, real-time, contrast-specific systems, it is now possible to detect a contrast leakage by using US. This finding opens new possibilities in the assessment and management of several abdominal emergencies, including trauma (initial workup and monitoring), spontaneous hematomas, and rupture of aneurysms or masses. This article describes the technique, findings, possibilities, and limitations of contrast-enhanced US in the evaluation of active abdominal bleeding.     

Hepatocellular carcinoma: therapeutic experience with percutaneous ethanol injection under real-time contrast-enhanced color Doppler sonography with the contrast agent Levovist.

OBJECTIVE: To describe our experience with percutaneous ethanol injection under real-time contrast-enhanced color Doppler sonography with Levovist (SH U 508A; Nihon Schering, Osaka, Japan) for hepatocellular carcinoma after transcatheter arterial infusion. METHODS: Twenty patients (17 men and 3 women; mean age, 58.4 years) with 23 hepatocellular carcinoma nodules (mean +/- SD, 2.7 +/- 1.5 cm) underwent percutaneous ethanol injection under real-time contrast-enhanced color Doppler sonography 1 week after transcatheter arterial infusion. Therapeutic effects were assessed by contrast-enhanced computed tomography and posttreatment fine-needle biopsy. This study was performed on a prospective basis. RESULTS: After the transcatheter arterial infusion, contrast-enhanced color Doppler sonography showed intense intratumoral color signals in all 23 hepatocellular carcinomas. After the percutaneous ethanol injection, contrast-enhanced color Doppler sonography, fine-needle biopsy, and contrast-enhanced computed tomography showed no color signals, no viable tumor tissues, and no enhancement in any of the 23 hepatocellular carcinomas. Three to 5 (mean, 3.3) percutaneous ethanol injection sessions with a 5.2- to 15.6-mL (mean, 12.8-mL) total volume of ethanol per tumor were required for complete disappearance of color signals on contrast-enhanced color Doppler sonography. CONCLUSIONS: Percutaneous ethanol injection under real-time contrast-enhanced color Doppler sonography has considerable efficacy in treating hepatocellular carcinoma.     

Evaluation using contrast-enhanced harmonic gray scale sonography after radio frequency ablation of small hepatocellular carcinoma: sonographic-histopathologic correlation.

OBJECTIVE: To evaluate the usefulness of contrast-enhanced harmonic wideband gray scale sonographic images obtained after radio frequency-induced coagulation necrosis, we compared the morphologic and histopathologic characteristics of the ablated tumors with sonographic images of the tumors. METHODS: Forty-eight patients with 72 hepatocellular carcinomas with a maximal diameter of 3 cm or less were treated percutaneously using radio frequency ablation. Six treated tumors in 4 patients were resected 1 month after ablation; the remaining 66 treated tumors were evaluated by a biopsy procedure performed with an 18-gauge fine needle 1 month after ablation. The excised tumors and biopsy specimens were then examined by histopathologic methods, and the findings were compared with those obtained on contrast-enhanced harmonic wideband gray scale sonography. Hematoxylin-eosin-stained specimens were inconclusive as to whether cellular viability remained; therefore, cell viability was determined by a positive result after histochemical (lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate-diaphorase) staining. RESULTS: Contrast-enhanced harmonic wideband gray scale sonography after radio frequency ablation showed residual tumor enhancement in 5 (6.9%) of the 72 tumors; the histopathologic results for these 5 tumors were also positive for tumor residue. The remaining 67 tumors (93.1%) did not show any residual tumor enhancement when examined by sonography; however, only 66 tumors did not reveal tumor residue when examined histopathologically. Contrast-enhanced harmonic wideband sonographic imaging provided results that were comparable with histopathologic findings, the criterion standard for diagnosis; the sensitivity and specificity of the sonographic images for the detection of residual tumor tissue in ablated tumors were 83.3% (5 of 6) and 100% (66 of 66), respectively. CONCLUSIONS: Contrast-enhanced harmonic wideband gray scale sonography is a potentially useful technique for evaluating the therapeutic effects of radio frequency ablation on hepatocellular carcinoma.     

Flash-echo contrast sonography in the evaluation of response of small hepatocellular carcinoma to percutaneous ablation

PURPOSE: To evaluate the use of flash-echo contrast sonography (FECS) in subtraction mode in assessing small hepatocellular carcinoma (HCC) after percutaneous local ablation therapy. METHODS: Between March 2000 and February 2002, we prospectively assessed small HCCs after percutaneous local ablation therapy using FECS in subtraction mode. Thirty-three patients (22 men, 11 women) with 35 tumors ranging in size from 1.1 to 3.0 cm (mean +/- SD, 2.0 +/- 0.5) were enrolled. Twenty-one tumors received percutaneous ethanol injection only, 13 tumors received percutaneous microwave ablation therapy only, and the remaining tumor received both treatments. CT, hepatic angiography, and follow-up were used as gold standards in analyzing the accuracy of FECS in detecting residual tumors. RESULTS: The agreements between FECS and CT, FECS and hepatic angiography, and all 3 imaging modalities were 80% (28/35), 85.7% (30/35), and 77.1% (27/35), respectively. Twenty-one patients with 23 completely ablated tumors were followed up for 5 to 39 months (mean +/- SD, 20.2 +/- 11.2). Recurrent disease was detected in 11 (52.4%) patients; local tumor recurrence occurred in 4 (17.4%) patients. The sensitivity, specificity, accuracy, and positive and negative predictive value of FECS in detecting viable tumors were 53.8% (7/13), 90.9% (20/22), 77.1% (27/35), 77.8% (7/9), and 76.9% (20/26), respectively. CONCLUSIONS: FECS in subtraction mode shows good agreement with hepatic angiography and CT in the assessment of small HCC after percutaneous local ablation therapy. The sensitivity of FECS in detecting residual tumors is suboptimal.     

Evaluation of the intratumoral vasculature of hepatocellular carcinoma by power Doppler sonography: advantages and disadvantages versus conventional color Doppler sonography

Background: To determine whether a difference exists in the relative ability of power Doppler sonography and conventional color Doppler sonography to detect the intratumoral vasculature of hepatocellular carcinoma based on lesion size and location. Methods: Sixty patients with 88 hepatocellular carcinoma lesions that showed tumor staining on angiography and were enhanced on dynamic computed tomography were evaluated. Power Doppler sonography and color Doppler sonography were used to detect the intratumoral vasculature, and their sensitivity to blood flow was evaluated. Results: Power Doppler sonography showed a superior detection rate for lesions smaller than 2 cm and located 4–8 cm from the abdominal surface in the right hepatic lobe as compared with color Doppler sonography (p < 0.01). Neither power Doppler sonography nor color Doppler sonography depicted the intratumoral vasculature of lesions located more than 8 cm from the abdominal surface (n = 14). Both color Doppler imagings exhibited a low detection rate for lesions in the left hepatic lobe (n = 31, p < 0.01). Conclusions: Power Doppler sonography should be applied in the evaluation of small or intermediate depth lesions because it is more sensitive to these lesions than color Doppler sonography, but it is not useful for left lobe and deep lesions. Received: 31 March 1999/Accepted: 14 July 1999     

超声造影谐频成像对原发性肝癌治疗效果的评价

目的：评价超声造影谐频成像在原发性肝癌治疗后疗效判断方面的作用。方法：使用Levovist对27例33个肝癌结节治疗前后分别行超声造影能量多普勒谐频成像和灰阶谐频成像数字减影检查,结果与动态增强CT相比较。结果：以动态增强CT结果为金标准,治疗前33个肝癌结节,超声造影增强的阳性率为93．9％（31／33）;而对治疗后肝癌,能量多普勒成像显示肿瘤内血流信号的敏感性,特性和准确性均为100％,灰阶谐频成像数字减影则分别为93．9％、100％和96．8％,结论：超声造影谐频成像可以敏感而直观地显示治疗后肿瘤内残存的血流信号,即时评估肿瘤的治疗效果,创伤小,值得临床推广。     

实时超声造影检测肝癌血供状况的研究

目的：探讨实时超声造影对肝癌血供情况判断的准确性。方法：对15例经手术病理证实的原发性肝细胞肝癌患者进行实时超声造影检查，造影剂为SonoVue，经肘部静脉弹丸注射。结果：注射SonoVue后15个病灶均快速增强，增强达峰值时，有8个病灶内部出现大小不一或不规则形的造影剂非填充区（低回声），与病理对照显示该低回声区为肿瘤坏死区域，并且大小及位置与标本显示相一致。结论：实时超声造影能反映肝癌的血供情况，对判断肿瘤有无坏死有很大帮助。     

Evaluation of hepatic focal nodular hyperplasia with contrast-enhanced gray scale harmonic sonography: initial experience.

OBJECTIVE: To assess the potential of contrast-enhanced gray scale harmonic sonography in the evaluation of the typical vascular and enhancement patterns of hepatic focal nodular hyperplasia. METHODS: Thirteen patients with 13 lesions of hepatic focal nodular hyperplasia underwent contrast-enhanced gray scale harmonic sonography. After the injection of a microbubble contrast agent (SH U 508A), gray scale harmonic sonographic studies using a Coded Harmonic Angio technique were performed with a combination of a period of continuous scanning to assess the vascular pattern (vascular imaging) and interval delay scanning to determine the sequential enhancement pattern (acoustic emission imaging). Each imaging pattern was categorized and analyzed by consensus of 2 experienced radiologists. RESULTS: In 12 (92%) of 13 lesions, vascular imaging during the arterial phase showed central arteries of a spoked wheel pattern, whereas the remaining lesion had stippled vascularity. On acoustic emission imaging, 11 (85%) of 13 lesions were hyperechoic during the early phase, and the remaining 2 (15%) were isoechoic compared with surrounding parenchyma. Ten (77%) of 13 lesions remained either hyperechoic (5 of 13) or isoechoic (5 of 13) during the delay phase, whereas the remaining 3 lesions (23%) were hypoechoic. CONCLUSIONS: Contrast-enhanced gray scale harmonic sonography showed the typical vascularity of a spoked wheel pattern during the vascular phase and persistent enhancement on serial acoustic emission imaging in most cases of hepatic focal nodular hyperplasia, and thereby it can be a promising technique in noninvasive diagnosis of this entity.     

Characterization of focal liver lesions: comparison of pulse-inversion harmonic contrast-enhanced sonography with contrast-enhanced CT

PURPOSE: To compare the efficacy of contrast-enhanced pulse-inversion harmonic sonography for the characterization of focal liver lesions with that of contrast-enhanced helical CT. METHODS: Real-time contrast-enhanced sonography (CEUS) using Sonovue and contrast-enhanced CT (CECT) were performed on 109 patients with focal liver lesions, including 61 hepatocellular carcinomas, 15 liver metastases, 5 cholangiocellular carcinomas, 12 hemangiomas, 5 regenerative nodules, 3 adenomas, 3 focal nodular hyperplasias, 4 focal necroses, and 1 angiomyolipoma prior to surgery or percutaneous needle biopsy. The diagnostic performance was assessed by using histopathological results as reference standards. RESULTS: Three cases were missed on CEUS, and 7 cases were missed on CECT. These 10 missed cases were excluded from paired statistical comparison. Ten cases were misdiagnosed on CEUS and 17 cases were misdiagnosed on CECT. The overall accuracy was 89.9% (89/99) for CEUS and 82.8% (82/99) for CECT. The difference between CEUS and CECT was not statistically significant. Concordance between CEUS and CECT was observed in 90.9% (90/99) cases. CONCLUSION: Real-time pulse-inversion harmonic CEUS with Sonovue is comparable with CECT in the characterization of focal liver lesions.     

Villous adenoma of extrahepatic bile duct: contrast-enhanced sonography findings

We report a case of villous adenoma in the extrahepatic bile duct that was successfully diagnosed with contrast-enhanced sonography (CEUS) before surgical resection. On baseline sonography, the mass appeared as a homogeneously isoechoic mass filling the bile duct from the confluence of the right and left hepatic ducts to the distal common bile duct. No intralesional flow signal was found on color Doppler imaging and power Doppler imaging. On CEUS, the mass showed homogeneous enhancement during arterial phase, thus confirming the neoplastic nature of the lesion. The enhancement decreased gradually so that the mass became hypoenhanced during portal and late phases. Surgical resection was performed, and pathologic examination confirmed a villous adenoma of the bile duct epithelium with mild dysplasia.     

Blunt hepatic trauma: evaluation with contrast-enhanced sonography: sonographic findings and clinical application.

OBJECTIVE: The purpose of this study was to report our initial experience in the assessment of liver trauma with real-time contrast-enhanced sonography (CES). METHODS: From January 2000 to December 2003, there were 431 hemodynamically stable patients evaluated with sonography for blunt abdominal trauma. Among these patients, 87 were selected to undergo second-level imaging, consisting of CES and computed tomographic (CT) evaluation. Indications for further assessment were baseline sonographic findings positive for liver injury, baseline sonographic findings positive for injury to other abdominal parenchyma, baseline sonographic findings positive for free fluid only, baseline sonographic findings indeterminate, and baseline sonographic findings negative with persistent clinical or laboratory suspicion. RESULTS: There were 23 hepatic lesions shown by CT in 21 patients. Peritoneal or retroperitoneal fluid was identified in 19 of 21 positive cases by all 3 imaging modalities. Liver injury was found in 15 patients on sonography and in 19 on CES. Contrast-enhanced sonography compared better than unenhanced sonography with the criterion standard for related injury conspicuity, injury size, completeness of injury extension, and involvement of the liver capsule. Both CES and CT showed intrahepatic contrast material pooling in 2 cases. All patients with false-negative sonographic or CES findings recovered uneventfully. CONCLUSIONS: Contrast-enhanced sonography is an effective tool in the evaluation of blunt hepatic trauma, being more sensitive than baseline sonography and correlating better than baseline sonography with CT findings. In institutions where sonography is regarded as the initial procedure to screen patients with trauma, this technique may increase its effectiveness. In addition, CES may be valuable in the follow-up of patients with conservatively treated liver trauma.     

Detection of hepatocellular carcinoma capsule by contrast-enhanced ultrasound using Levovist: correlations with pathological findings

Purpose To determine the most appropriate therapy for each hepatocellular carcinoma (HCC) nodule, it is important to ascertain whether the tumor has a capsule. The aim of this study was to investigate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in HCC capsule detection by comparing ultrasound findings with histological results from operative specimens. Methods Thirty-six HCC nodules (all smaller than 5 cm) from 36 patients who had undergone hepatectomy were examined by CEUS using Levovist with agent detection imaging. The vascular phase images and time course changes of HCC were observed after a bolus injection of Levovist. We classified the appearance of the tumor artery, tumor enhancement, and washout into several patterns. We grouped HCCs into encapsulated or nonencapsulated on the basis of the histology of the operative specimens, taking into account the effectiveness of transcatheter arterial chemoembolization. Ultrasound and pathological findings were compared to assess the ability of CEUS to detect HCC capsules. Results During the arterial phase, 12 (80.0%) encapsulated and 3 (14.3%) nonencapsulated HCC nodules showed a surrounding artery with branches pattern (P < 0.0001). The sensitivity, specificity, and accuracy of this pattern for HCC capsule detection were 80%, 86%, and 83%, respectively. A branching artery was found in 15 (71.4%) nonencapsulated but in only 3 (20.0%) encapsulated HCC nodules (P < 0.01). The sensitivity, specificity, and accuracy of this branching artery pattern for confirming the absence of a capsule in HCC nodules were 71%, 80%, and 75%, respectively. Almost all HCC nodules showed strong–moderate or weak enhancement and strong–moderate or mild washout. Neither enhancement nor washout pattern correlated with the presence of a capsule. Conclusion The arterial phase of CEUS is very useful for detection of HCC capsules and therefore facilitates selection of the most appropriate treatment method for HCC.     

实时灰阶超声造影评价肝癌动物模型抗血管生成治疗的研究

SI)、曲线下面积(AUC)和血流量系数(BF)明显低于对照组,另外峰值减半斜率(a2)和曲线上升斜率(a3)明显大于对照组(P<0.05).定量参数与肿瘤体积增长率正相关(P<0.05).a3和ISI与坏死指数负相关(r=-0.54,P=0.008;r=-0.46,P=0.027).结论 实时灰阶超声造影能反映肿瘤内血流灌注变化,有助于监测肿瘤抗血管生成治疗的血管反应.     

Sclerosing hepatocellular carcinoma: Radiologic findings

The radiologic findings of seven patients with sclerosing hepatocellular carcinoma (HCC), an unusual subtype of HCC, were evaluated. Computed tomography (CT) demonstrated a hypointense mass with marked delayed contrast enhancement. Although the tumor was well-defined, the tumor capsule was not seen. Focal atrophy was seen in four patients. Ultrasound (US) showed an isoechoic to hyperechoic mass without a rim. Angiography revealed prominent tumor vessels and prolonged stains in all cases. Arterial encasement was seen in four patients. On magnetic resonance (MR) imaging, all tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. On dynamic MR study, remarkable contrast enhancement, which continued to the delayed phase, seemed to be characteristic for sclerosing HCC. In the presence of liver tumors with homogeneous architecture, hypervascularity, prolonged enhancement, absence of tumor capsule, and focal atrophy in high-risk patients of HCC, sclerosing HCC should be considered.     

Contrast-enhanced power Doppler sonography and helical computed tomography for assessment of vascularity of small hepatocellular carcinomas before and after percutaneous ablation

PURPOSE: We compared the usefulness of Levovist-enhanced power Doppler imaging (PDI) and helical CT in the depiction of tumor vascularity before and after percutaneous ablation of small hepatocellular carcinomas (HCCs). METHODS: Thirty-one cirrhotic patients with solitary unresectable HCCs smaller than 5 cm (mean size, 2.7 +/- 0.8 cm; range, 1.5-5.0 cm) recruited over a 15-month period were treated with percutaneous ethanol injection (n = 9) or radiofrequency ablation (n = 22). PDI, contrast-enhanced PDI (using Levovist), and multiphase contrast-enhanced helical CT were performed before and after percutaneous ablation, and vascularity findings were compared. RESULTS: Levovist significantly increased baseline intratumoral Doppler signals on PDI compared to non-contrast PDI. The most frequent tumor vascularity pattern was heterogeneous (45%). Vascularity was identified in all tumors by both contrast-enhanced PDI and helical CT before ablation. After percutaneous ablation, intratumoral vascularity was detected in 11 tumors by contrast-enhanced PDI and in 15 tumors by CT. The sensitivity, specificity, and diagnostic accuracy of contrast-enhanced PDI in demonstrating intratumoral vascularity, with CT being the gold standard, were 66%, 93%, and 81%, respectively. There was significant agreement between the 2 modalities in the depiction of tumor vascularity after ablation (kappa = 0.6, p = 0.001). However, there were 5 false negatives and 1 false positive with contrast-enhanced PDI. Complete tumor necrosis was achieved in 21 patients (68%). CONCLUSIONS: There was a good concordance between contrast-enhanced PDI and helical CT in the depiction of HCC vascularity before and after percutaneous ablation. However, although contrast-enhanced PDI may be useful for real-time guidance of treatment, its low sensitivity makes it inadequate to accurately assess the completeness of ablation.     

Assessment of the therapeutic response of hepatocellular carcinoma treated with transcatheter arterial chemoembolization: comparison of contrast-enhanced sonography and 3-phase computed tomography.

OBJECTIVE: The purpose of this study was to compare contrast-enhanced sonography with 3-phase computed tomography (CT) in assessing the therapeutic response of hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE). METHODS: Twenty-nine nodular HCCs treated with TACE were examined with contrast-enhanced sonography, 3-phase helical CT, and conventional angiography. Contrast-enhanced sonographic and CT findings were interpreted separately and prospectively for the presence or absence of contrast enhancement in the treated HCCs. Conventional angiography served as the reference standard. RESULTS: Intratumoral enhancement was seen in 19 HCCs (61%) on contrast-enhanced sonography and 12 HCCs (39%) on CT. Enhancement patterns on sonography were blush in 8 (42%), branching in 2 (11%), nodular in 4 (21%), and stippled in 5 (26%). Of the 19 HCCs with intratumoral enhancement on contrast-enhanced sonography, 13 (68%) showed tumor staining on angiography. Of the 12 HCCs without intratumoral enhancement on sonography, 1 (8%) showed tumor staining on angiography. The sensitivity and specificity of contrast-enhanced sonography in depicting flow in HCCs treated with TACE were 93% and 65%, respectively. The sensitivity and specificity of 3-phase CT were 64% and 100%. CONCLUSIONS: Contrast-enhanced sonography is a more sensitive imaging method than 3-phase CT in depicting vascularity in HCCs treated with TACE.