Differential diagnosis of nodular lesions in cirrhotic liver by post-vascular phase contrast-enhanced US with Levovist: comparison with superparamagnetic iron oxide magnetic resonance images

Background We investigated the diagnostic utility of post-vascular phase contrast-enhanced ultrasonography (US) and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) as compared to the histological diagnosis of differential grades of hepatocellular carcinomas (HCCs). Methods Forty-nine patients with histologically characterized liver nodules (well-differentiated HCC, n = 20; moderately differentiated HCC, n = 19; poorly differentiated HCC, n = 1; dysplastic nodule, n = 9) received contrast-enhanced US and SPIO-MRI. Subsequently, we quantitatively evaluated the relationships between the images of the nodules and their histological diagnosis and differential grades. Results The ratio of the echogenicity of the tumorous area to that of the nontumorous area with post-vascular phase contrast-enhanced US (post-vascular phase ratio) decreased as nodules became less differentiated (P < 0.05; Kruskal-Wallis test). The ratio of the intensity of the nontumorous area to that of the tumorous area on SPIO-enhanced MR images (SPIO intensity index) also decreased as nodules became less differentiated (P < 0.01). The post-vascular phase ratio correlated with the SPIO intensity index for HCCs and dysplastic nodules (r = 0.76). The conformity of the result from the post-vascular phase contrast-enhanced US and SPIO-MRI was 96%. Conclusions Contrast-enhanced US is a valuable method for predicting the histological grade of HCCs in cirrhotic patients, and may be a good alternative to SPIO-enhanced MRI.     

1.5 Harmonic Imaging Sonography with microbubble contrast agent improves characterization of hepatocellular carcinoma

AIM: To investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma (HCC) and for the evaluation of therapeutic response. METHODS: Phantom experiments were performed to compare the contrast effects of 2nd harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC (42 nodules) before and after the treatment and to compare against the findings obtained using other diagnostic imaging modalities. RESULTS: In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules (85.7%) during the early phase and in all 42 nodules (100%) during the late phase using 1.5 Harmonic Imaging Sonography, in 38 nodules (90.5%) using contrast-enhanced CT, in 34 nodules (81.0%) using digital subtraction angiography (DSA), and in 42 nodules (100%) using US CO2angiography. Following transcatheter arterial embolization, 1.5 Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules (47.6%). However, 6 of these 20 cases were not judged in contrast-enhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO2 angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%, respectively. CONCLUSION: 1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated. Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial embolization on HCC.     

Usefulness of contrast-enhanced perfusional sonography in the assessment of hepatocellular carcinoma hypervascular at spiral computed tomography

BACKGROUND/AIMS: Diagnosis of hepatocellular carcinoma (HCC) relies strongly on the detection of hypervascularity in the arterial phase and, in this setting, spiral computed tomography (CT) is the most widely used method. This prospective study aimed to investigate the usefulness of low mechanical index harmonic ultrasound (US), using a second generation contrast-enhanced technique, in the assessment of vascular pattern of HCC shown to be hypervascular at spiral CT. METHODS: A total of 79 cirrhotic patients with 103 nodules (mean+/-SD 28+/-13 mm) with arterial hypervascularity at spiral CT were studied. US examination was performed by perfusional sonography, using a new dedicated technology (CnTI-Esaote trade mark ), operating at low mechanical index, after injection of a second generation contrast agent (SonoVue trade mark -Bracco), allowing detection of tumoral flow during arterial phase. RESULTS: Selective arterial enhancement on perfusional sonography was observed in 94 /103 nodules (91.3%), with a sensitivity of 66.6, 87.5, 91.7, and 97.3% in nodules 123 cm respectively. CONCLUSIONS: Perfusional sonography shows good diagnostic agreement with spiral CT in hypervascular HCC and may be proposed for the immediate vascular characterization of nodules detected at US and used as second imaging technique to confirm hypervascularity in cirrhotic nodules.     

Effectiveness of real-time virtual sonography-guided radiofrequency ablation treatment for patients with hepatocellular carcinomas.

Aim: Real-time virtual sonography (RVS) can synchronize B-mode ultrasound (US) images with multiplanar reconstruction (MPR)-computed tomography (CT) images on the same screen in real time. The purpose of this study was to evaluate the effectiveness of RVS for radiofrequency ablation therapy (RFA) of hepatocellular carcinomas (HCC) in which it was difficult to identify contours or margins by B-mode US. Methods: Sixty-three consecutive patients with a solitary HCC of less than 3.5 cm in diameter were enrolled in this study. Thirty-nine patients with HCC clearly detectable by B-mode US underwent conventional RFA, while the remaining 24 with obscure tumor lesions underwent RVS-guided RFA. A follow-up study of RFA treatment was performed every 3 months using enhanced CT imaging of the arterial and portal phase (at least 24 months). The accuracy of needle insertion was confirmed by measuring the gap between the needle insertion line and the center of the tumor from MPR-CT images. Results: The local recurrence rate of the RVS-guided RFA group was similar to that of the conventional RFA group (8.3% vs 7.7%), despite the difficulty of detecting tumor lesions in the former group. The mean gap between the needle insertion line and the center of the tumor was 1.6 mm (0-3.2 mm) in eight patients treated with RVS-guided RFA. Conclusion: RVS-guided RFA can be useful for treating HCC that are difficult to detect by B-mode US.     

New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma

Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.     

Contrast-enhanced Doppler ultrasonography in the diagnosis of hepatocellular carcinoma and premalignant lesions in patients with cirrhosis.

Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerative nodules, dysplastic nodules, and hepatocarcinoma. The aim of this study was to establish whether contrast-enhanced Doppler ultrasonography (US) is able to distinguish between early hepatocellular carcinoma (HCC) and small nonmalignant nodules in cirrhosis. Between January 1998 and December 1999, 500 cirrhotic patients with no previous history of HCC or evidence of hepatic focal lesions were enrolled and prospectively followed-up with US every 6 months until December 2000. Sixty-one patients developed focal lesions, 12 multifocal, and 49 monofocal. Biopsy of focal lesions, contrast-enhanced Doppler US, and spiral computed tomography (CT) were performed in 41 consecutive patients with small (<3 cm) monofocal lesions. Twenty nodules were diagnosed as HCC and 21 as nonmalignant (14 large regenerative nodules, 3 low-grade, and 4 high-grade dysplastic nodules) by liver biopsy. Intratumoral arterial blood flow was detected in 19 of 20 (95%) HCC and 6 of 21 (28%) nonmalignant nodules by contrast-enhanced Doppler US (P<.0001). The mean peak resistance and pulsatility indices were 0.82 +/- 0.09 and 1.56 +/- 0.2 in HCC and 0.62 +/- 0.08 and 0.82 +/- 0.08 in dysplastic lesions (P =.002 and.0001), respectively. Spiral CT revealed arterial perfusion in 19 of 20 HCC and in 4 of 21 nonmalignant nodules (high-grade dysplastic nodules). Four of the apparently false-positive nodules at enhanced Doppler US were high-grade dysplastic nodules and 2 evolved to HCC during follow-up. In conclusion, contrast-enhanced Doppler US is a noninvasive, very sensitive technique in differentiating malignant and premalignant lesions from nonmalignant focal lesions in the liver.     

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma （HCC） in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase.Contrast-enhanced computed tomography （CT） revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase.Magnetic resonance imaging （MRI） revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hvoerintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC.Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically,the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.     

Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma

Background

We evaluated the sensitivity and specificity of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography (CEUS) using perflubutane microbubbles (Sonazoid) in comparison with conventional B-mode ultrasonography (US) for the detection of hepatocellular carcinoma (HCC) nodules.

Methods

A total of 100 treatment-na?ve HCC patients admitted at our hospital between December 2007 and June 2009 were consecutively enrolled. The sensitivity and specificity of conventional and contrast-enhanced US were evaluated on a liver segment basis using dynamic CT as a reference standard. Movie files of conventional and enhanced US were stored separately for each segment (e.g., lateral, medial, anterior, and posterior) and reviewed randomly by two blinded readers.

Results

A total of 138 HCC nodules (mean diameter 20.3?mm) were detected in 123 of 400 segments. Detection sensitivity of B-mode US was 0.837 for reader A and 0.846 for reader B, and that of CEUS was 0.732 for reader A and 0.831 for reader B. Specificity of B-mode US was 0.902 for reader A and 0.949 for reader B, and that of CEUS was 0.986 for reader A and 0.978 for reader B. CEUS false positives were mainly due to misidentification of hepatic cysts. A significant proportion of false-negative nodules are hyperechoic in B-mode US, likely because echogenicity hampers visualization of the defect in Kupffer imaging.

Conclusions

Kupffer imaging by CEUS with Sonazoid showed very high specificity but rather mediocre sensitivity for HCC detection. CEUS is highly suitable for confirmatory diagnosis of HCC; however, caution should be exercised in reaching a diagnosis based only on CEUS.     

Usefulness of the hyperechoic rim for assessing the therapeutic efficacy of radiofrequency ablation in hepatocellular carcinoma patients

Aim:  During radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), a hyperechoic rim develops around the HCC nodules. The usefulness of the hyperechoic rim to guide treatment was assessed.
Methods:  RFA was first performed in pig livers to determine the significance of the hyperechoic rim. Fifty-five patients with 75 HCC nodules had received RFA for the treatment of HCC. For those patients, we evaluated whether conventional ultrasonography (US) could be used instead of contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS) using virtual imaging. Finally, 31 patients with 45 HCC nodules received RFA, and the degree of ablation was assessed based on the hyperechoic rim. Repeated RFA was done when ablation appeared incomplete.
Results:  In the pig livers, the hyperechoic rim was found to be related to the presence of dead cells. The preliminary study showed that US could be used instead of CECT and CEUS to evaluate the degree of ablation caused by RFA. Because hepatic vessels in the back side of the hyperechoic rim were not clear by the artifact, we used the distance from the surface of the liver to the hyperechoic rim for evaluation. By analyzing the extent of the hyperechoic rim, it was noted that incomplete ablation was achieved in 17 of 31 patients (21 of 45 HCC nodules). These patients were re-treated with RFA within 5–15 min of the first RFA.
Conclusion:  This study shows that the hyperechoic rim is related to the presence of dead and necrotic tissues. Thus, assessment of the hyperechoic rim's characteristics allows one to evaluate the efficacy of RFA.     

MRI versus 64-row MDCT for diagnosis of hepatocellular carcinoma

AIM: To compare the diagnostic capability of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC) tumour nodules and their effect on patient management.METHODS: A total of 28 patients (25 male, 3 female, mean age 67 ± 10.8 years) with biopsy-proven HCC were investigated with 64-row MDCT (slice 3 mm native,arterial and portal-venous phase, 120 mL Iomeprol,4 mL/s, delay by bolus trigger) and MRI (T1fs fl2d TE/TR 2.72/129 ms, T2tse TE/TR 102/4000 ms, 5-phase dynamic contrast-enhanced T1fs fl3d TE/TR 1.56/4.6,Gadolinium-DTPA, slice 4 mm). Consensus reading of both modalities was used as reference. Tumour nodules were analyzed with respect to number, size, and location.RESULTS: In total, 162 tumour nodules were detected by consensus reading. MRI detected significantly more tumour nodules (159 vs 123, P < 0.001) compared to MDCT, with the best sensitivity for early arterial phase MRI. False-negative CT findings included nodules ≤ 5 mm ( n = 5), ≤ 10 mm ( n = 17), ≤ 15 mm ( n = 12 ), ≤ 20 mm ( n = 4 ), and 1 nodule > 20 mm. MRI missed 2 nodules ≤ 10 mm and 1 nodule ≤ 15 mm. On MRI, nodule diameters were greater than on CT (29.2 ± 25.1 mm, range 5-140 mm vs 24.1 ± 22.7 mm, range 4-129 mm, P < 0.005). In 2 patients, MDCT showed only unilobar tumour spread, whereas MRI revealed additional nodules in the contralateral lobe. Detection of these nodules could have changed the therapeutic strategy. CONCLUSION: Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC nodules. Patients should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.     

Recent advances in the diagnosis of hepatocellular carcinoma

In the last decade, new imaging techniques have become available, offering the possibility of investigating contrast perfusion of liver nodules in cirrhosis. It is now accepted that a non-invasive diagnosis of hepatocellular carcinoma (HCC) can be established based on the vascular pattern, obtained with pure blood pool contrast agents. The diagnostic pattern includes: hypervascularity in the arterial phase (15–35 s after contrast injection), consisting in a contrast signal in the nodule greater than in the surrounding parenchyma, followed by contrast wash out, which leads the nodule to show the same, or, more specifically, a lower contrast signal, than the surrounding parenchyma in the portal and late phases (>40 s after injection). Such a pattern can be obtained not only by computed tomography or magnetic resonance imaging, but also by contrast-enhanced ultrasonography, most simply with real-time low mechanical index harmonic imaging ultrasound equipment with second-generation ultrasound contrast agents. The risk of false-positive diagnosis of malignancy isnearly abolished when the functional vascular pattern is not the only feature, but is superimposed on a nodule visible also without contrast. One single contrast imaging technique may suffice to make a diagnosis of HCC if the nodule is >1 cm in diameter and has developed during a surveillance program. Other types of contrast agents, such as those taken up by the reticular-endothelial system cells, may offer additional diagnostic clues, but definitive evidence of their efficacy is still to be produced. In conclusion, contrast-enhanced imaging techniques now offer the possibility of a non-invasive diagnosis of HCC in a large number of cases, reducing the need of invasive investigations, such as ultrasound-guided biopsy or angiography.     

Management of small hepatocellular carcinoma

In the last years the incidence of hepatocellular carcinoma (HCC) is rising in cirrhotic patients worldwide. Due the importance of early and definite diagnosis of HCC, any nodular lesion detected in patients with chronic liver disease should be considered as suspicious for HCC. The screening and surveillance programs in patients with liver diseases have increased the number of small HCC detected at an early stage, when the therapeutic options available are able to provide benefit. The introduction of new imaging techniques has improved the accuracy of characterizing these nodules. According to the EASL recommendations, contrast-enhanced computed tomography (CT), contrast enhanced ultrasound (US) and magnetic resonance (MR) with different MR-contrast agents are currently used to characterize liver lesions. Imaging guided biopsy is recommended for small nodules or in lesions without typical features (arterial hypervascularization) in at least two imaging techniques. Frequently the differential diagnosis of small nodules is complicated by discordant vascularity and recent studies have also demonstrated the presence of small hypovascular HCC at perfusional US and helical CT. At present, different treatment options can be offered to patients with diagnosis of small HCC at an early stage; percutaneous techniques, surgical resection and liver transplantation can provide benefit in properly selected patients. This review describes some critical points regarding the detection, diagnosis and therapeutic management of small nodules of HCC in cirrhotic patients.     

Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.

AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients. PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study. CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.     

Well-to moderately-differentiated HCC manifesting hyperattenuation on both CT during arteriography and arterial portography

We present a rare case of well- to moderatelydifferentiated hepatocellular carcinoma （HCC） in a 71-year-old woman with hepatitis C virus-related cirrhosis and unusual radiologic features. A 20-mm hypoechoic nodule disclosed by ultrasound in segment two showed hyperattenuation on both computed tomography hepatic arteriography and computed tomography during arterial portography. Contrast-enhanced ultrasound revealed hypervascularity in the early vascular phase and defect in the post-vascular phase, with the same pattern detected by the two imaging techniques. SPIO-MRI revealed a hyperintense nodule. These findings were compatible with those of moderately-differentiated HCC. An ultrasound-guided biopsy showed histological features of well- to moderately-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, fatty change, clear cell change and mild cell atypia with a thin to mid-trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.     

Well-differentiated HCC manifesting hyperattenuation on CT during arterial portography

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis, with unusual radiologic features, is presented. A 10-mm hypoechoic nodule disclosed by ultrasound in segment six showed hypoattenuation on computed tomography hepatic arteriography and hyperattenuation on computed tomography during arterial portography, indicating that the portal vein may have been the dominant vascularity of the nodule. Contrast-enhanced ultrasound revealed hypovascularity in the early arterial phase, isovascularity in the late vascular phase, and the same perfusion as that surrounding the liver parenchyma in the post-vascular phase, with the same pattern observed on the two imaging techniques. These findings were considered not compatible with those of well-differentiated HCC. Ultrasound-guided biopsy showed histological features of well-differentiated HCC with over two-fold the cellularity of the non-tumorous area with a high nuclear/cytoplasmic ratio, increased cytoplasmic eosinophilia, slight atypia and fatty change with an irregular thin trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.     

Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma

Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is based on ultrasound (US) examinations performed at either 6 or 12 month intervals. Early detection of HCC in patients with cirrhosis is a challenging issue, since the different entities that are involved in the multi-step process of hepatocarcinogenesis--such as low-grade and high-grade dysplastic nodule--share common US features. Contrast-enhanced US allows reliable detection of arterial neoangiogenesis associated with a malignant transformation. Several reports have shown that the ability of contrast-enhanced US to diagnose HCC currently approaches that of optimized multidetector computed tomography (CT) or dynamic magnetic resonance (MR) imaging protocols. The use of contrast-enhanced US to characterize nodular lesions in cirrhosis has been recently recommended by the clinical practice guidelines issued by the European Federation of Societies for Ultrasound in Medicine and Biology and the American Association for the Study of Liver Diseases. However, contrast-enhanced US has not resulted in any significant improvement in the ability of US to detect small tumor foci, since a comprehensive assessment of the whole liver parenchyma cannot be accomplished during the short duration of the arterial phase. Hence, CT or MR imaging are still mandatory for proper intrahepatic staging of the disease.     

Differentiation between malignant and benign nodules in the liver： Use of contrast C^3-MODE technology

AIM: To investigate the value of contrast-enhanced C3-MODE technology in differentiating malignant nodules of liver from the benign ones. METHODS: Forty-six nodules in 36 patients (29 men and 7 women) were studied by contrast-enhanced C3-MODE technology and contrast-enhanced CT in 1 wk before the biopsy or operation. A low MI monitor and a high MI flash imaging were intermittently performed. After the injection of contrast agent, the period from 10 to 30 s and the time later than 100 s were respectively defined as early arterial phase and the late phase. The vascularities of the liver nodules in the two phases were combined for differential diagnosis. Corresponding to the pathological diagnosis, the accuracy, sensitivity and specificity of contrast-enhanced C3-MODE technology were compared to those of contrast-enhanced CT. RESULTS: By C3-MODE technology, 33 of the 46 liver nodules were demonstrated as defected area in the late phase and were diagnosed as malignant tumors. Of them, 28 with hypervascularity in the early arterial phase were assessed as hepatocellular carcinoma, the other five nodules with rim-like enhancement in the early arterial phase were diagnosed as metastatic tumors. Thirteen nodules were shown as iso or hypervascularity in the late phase as well as centripetal filling in the early arterial phase and we made a diagnosis of hemangioma. Corresponding to the pathological results, the sensitivity, specificity and accuracy of contrast-enhanced C3-MODE technology in differentiating malignant and benign nodules in the liver were 97.0%, 92.3% and 95.7%, respectively. With comparison to those of contrast CT (sensitivity, 94.1%; specificity, 91.7%; accuracy, 93.5%), the difference was not significant. CONCLUSION: Contrast-enhanced C3-MODE technology can effectively differentiate malignant liver tumors from the benign nodules. It highly agrees diagnostically with the pathology. We suggest that it provides a new approach for differential diagnosis of liver nodules in addition to contrast-enhanced CT.     

Comparative study of shear wave velocities using acoustic radiation force impulse technology in hepatocellular carcinoma: the extent of radiofrequency ablation

Background/Aims

The purpose of this study was to assess the value of acoustic radiation force impulse (ARFI) for predicting the extent of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) by correlating the elasticity of HCC and peritumoral parenchyma (as measured by ARFI) with the extent of ablation determined by computed tomography (CT).

Methods

From September 2009 to June 2011, 158 patients underwent RFA ablation for HCC (single, ≤3 cm). We evaluated the data of a total of 38 prospectively enrolled patients who underwent both ARFI imaging and contrast-enhanced CT after one session of 12 minutes of RFA without a change in needle position. The ARFI imaging indices, including the mean shear wave velocity (SWV) of HCC, mean SWV of the peritumoral parenchyma and tumor size, were evaluated to determine the statistical correlation with RFA extent after one session of 12 minutes of RFA.

Results

A stiffer liver parenchyma in patients with cirrhosis results in a smaller ablation zone.

Conclusions

SWV of ARFI in liver parenchyma was well correlated with RFA extent. After evaluating the correlation between ARFI and RFA extent, we suggest that the SWV in liver parenchyma might be a non-invasive supplementary tool for predicting the extent of RFA.     

Tumor hemodynamics in hepatic nodules associated with liver cirrhosis: relationship between cancer progression and tumor hemodynamic change]

Tumor hemodynamics including arterial vascularity (AV) and portal perfusion (PP) were evaluated in histologically confirmed 55 hepatic nodules associated with cirrhosis using ultrasonographic (US) angiography during intraarterial carbon dioxide microbubbles injection and CT during arterial portography. Tumor hemodynamic patterns were classified into 6 types as follows: Type I (n = 10): PP (+), AV (hypo); Type I' (n = 2): PP (+), AV (iso); Type II (n = 5): PP (-), AV (hypo); Type III (n = 8): PP (-), AV (iso); Type IV (n = 25): PP (-), AV (hyper), Type V (n = 5): PP (partially +), AV (vascular spot in hypovascular). Eight nodules of Type I were diagnosed as benign nodules histologically including adenomatous hyperplasia (AH) (n = 6) and regenerative nodule (n = 2). Hundred percent (5/5) of Type II and 88% (7/8) of Type III nodules were well-differentiated HCC, in contrast to 8% (2/25) of Type IV nodules, typical HCCs. Fatty metamorphosis was observed in 75% (6/8) of Type III nodules, in contrast to 16% (4/25) of typical (classical) HCC nodules (Type IV). We concluded that at the malignant transformation from AH to HCC, reduction of portal blood flow in the nodule precedes the initiation of the increase of the arterial tumor vessel. Moreover, early stage HCC could exhibit hypovascular (Type I, II), isovascular (Type III), or vascular spot in hypovascular pattern (Type V) compared with a typical HCC (Type IV). It was also suggested that the more mature as a neoplasms the HCC becomes, the more the arterial tumor vessel in the nodule increases and fatty metamorphosis of well-differentiated HCC is highly related with tumor hemodynamic condition, i.e., hypoperfusion state from both arterial and portal vessel.     

Contrast-enhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to compare contrast-enhanced gray-scale harmonic ultrasound with multiphasic spiral computed tomography in the assessment of treatment efficacy of non-surgically treated HCC. METHODS: We studied 56 HCCs treated by percutaneous ethanol injection (31 cases), radiofrequency ablation (three cases), trans-arterial chemoembolization (12 cases), and combined treatment (10 cases). The efficacy of therapies was blindly assessed by multiphasic computed tomography and gray-scale harmonic ultrasound with a second-generation contrast agent (sulfur hexafluoride). RESULTS: On computed tomography 30 tumors (53.6%) showed complete necrosis, while 26 lesions (45.4%) were still viable. On contrast-enhanced ultrasound examination 33/56 nodules (58.9%) had no contrast enhancement in the arterial phase, while 23/56 lesions (41.1%) were still vascularized. All the nodules assessed as completely necrotic on computed tomography did not show arterial enhancement on contrast-enhanced ultrasound and diagnostic agreement was found in 53/56 cases (94.6%) (P<0.001). Contrast-enhanced ultrasound demonstrated relative sensitivity and specificity of 87.0% and 98.4%. CONCLUSIONS: Contrast-enhanced harmonic ultrasound is promising in the efficacy evaluation of ablation treatments for HCC. Nodules vascularized in the arterial phase on contrast harmonic ultrasound should be considered still viable and addressed to additional treatment without further evaluation.