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Abstract: Purpose: Imaging-based differentiation of hepatic lesions (≤30mm) between well-differentiated hepatocellular carcinomas (w-HCC) and regenerative nodules (RN) presents difficulties. The aim was to compare the diagnostic abilities to differentiate w-HCC from RN using contrast-enhanced ultrasound and magnetic resonance imaging (MRI) both with liver-specific contrast agents. Materials and methods: This prospective study included 67 pathologically proven hepatic lesions (17.5±5.4mm, 54 w-HCCs, 13 RNs) in 56 patients with chronic hepatitis/cirrhosis (male 40, female 16; 29–79y). Hepatic-arterial/liver-specific phase enhancements were assessed quantitatively by ultrasound with perflubutane microbubble agent and MRI with gadolinium-ethoxybenzyl-diethylenetriamine with respect to the histological findings. Results: Sensitivity, specificity and accuracy of hepatic-arterial phase hyper-enhancement for w-HCC were 59.3%, 100% and 67.2% by ultrasound and 46.3%, 100% and 56.7% by MRI without significant difference. Meanwhile, those of liver-specific-phase hypo-enhancement for w-HCC were 44.4%, 100% and 55.2% by ultrasound and 87.0% (p <0.0001), 46.2% (p =0.0052) and 79.1% (p =0.0032) by MRI. Diagnostic accuracies for w-HCC by area under the receiver operating characteristic curves were higher in the hepatic-arterial phase in ultrasound (0.8316) than MRI (0.6659, p =0.0101) and similar in the liver-specific phase in ultrasound (0.7225) and MRI (0.7347, p =0.8814). Conclusions: Hypervascularity is a significant feature which distinguishes w-HCC from RN, and ultrasound exerts a beneficial impact better than MRI for such characterization. However, both imaging have comparable abilities in the characterization of non-hypervascular lesions, compensating mutually for the poor sensitivity of ultrasound and the poor specificity of MRI in the liver-specific phase. [Copyright &y& Elsevier]

Objective. To determine the safety and efficacy of anticoagulation treatment for portal vein thrombosis in cirrhosis patients with acute variceal bleeding, with patient eligibility determined by contrast ultrasonography findings. Materials and methods. This prospective study included 23 consecutive cirrhosis patients (63.8 ± 11.8 years old, 12 males and 11 females) with emergency admission for acute variceal bleeding with or without portal vein thrombus. Eligibility for anticoagulation treatment was determined by positive intra-thrombus enhancement on contrast ultrasonography (perflubutane microbubble agent, 0.0075 mL/kg) performed before endoscopy. Low-molecular-weight heparin was administered after hemostasis was achieved by band ligation. Repeated band ligation or injection sclerotherapy combined with argon plasma coagulation was performed for variceal disappearance. Results. Hemostasis was achieved in all 10 patients with active bleeding. Five of these patients had portal vein thrombus, and all showed positive intra-thrombus enhancement on contrast ultrasonography. Anticoagulation treatment of these five patients resulted in complete recanalization of the portal vein within 2-11 days. There were no significant differences in the number of endoscopic treatment sessions or the length of hospital stay between the groups with and without thrombosis, and no complications including rebleeding were reported. Long term, none of the patients who continued oral anticoagulation treatment had recurrence of thrombosis (4/5). Variceal recurrence occurred only in the non-thrombosis group (2/18) during the follow-up period (median: 351 days). Conclusions. Early anticoagulation treatment in cirrhosis patients with portal vein thrombosis and acute variceal bleeding may be safe, tolerated, and effective in cases with positive intra-thrombus enhancement on contrast ultrasonography. [ABSTRACT FROM AUTHOR]

Abstract: This prospective study aimed to elucidate the possibility of differentiating well-differentiated hepatocellular carcinoma (wHCC) from regenerative nodule (RN) on the basis of the heterogeneity of microbubble accumulation. Intensity analysis was conducted on early-phase and late-phase (60 s and 900 s post-injection; perflubutane microbubble) harmonic sonograms in 33 focal hepatic lesions (≤15 mm; 30 patients with chronic liver disease) that were histologically proven as wHCC or RN. Heterogeneity of enhancement, an average of standard deviation of late-phase enhancement in three different sections in the lesions with late-phase iso-enhancement, was examined with respect to the histologic findings. Heterogeneity of enhancement was higher in wHCC (28.7 ± 3.8) than RN (19.8 ± 2.1, p = 0.0213) in the 29 late-phase iso-enhancement lesions. The best cut-off value of the heterogeneity for the diagnosis of wHCC was 25.58, and the sensitivity and specificity were 77.8% and 100%, respectively. A novel parameter, heterogeneity of microbubble accumulation, facilitates differentiation between wHCC and RN showing a late-phase, iso-enhancement appearance. [Copyright &y& Elsevier]

Background/aims: Microbubble behaviour from the portal vein to the liver parenchyma may reflect haemodynamic changes because of hepatic fibrosis. The aim of this study was to determine the efficacy of contrast-enhanced ultrasound (US) with Sonazoid™ for the assessment of the grade of hepatic fibrosis. Methods: This prospective study evaluated 117 patients with chronic liver disease (chronic hepatitis 85; cirrhosis 32) and 34 controls. All subjects received both contrast-enhanced US with Sonazoid™ for 1 min after the agent injection and subsequent liver biopsy. Flow velocity and flow volume in the right portal vein, onset time of contrast enhancement in the right hepatic artery and right portal vein, maximum intensity ratio between the intra-hepatic portal vein and liver parenchyma, and time interval between the onset time and the time of maximum intensity ratio were compared with the pathological findings. Results: Among the evaluated parameters, time interval between the onset time and the time of maximum intensity ratio showed the closest relationship with the grade of hepatic fibrosis: 4.21 ± 1.32 for controls ( n=34), 5.58 ± 1.39 for F1 ( n=31), 6.79 ± 1.77 for F2 ( n=28), 8.85 ± 1.97 for F3 ( n=26) and 14.3 ± 3.49 for cirrhosis ( n=32); controls vs. F2, P=0.0004; F1 vs. F3, P<0.0001; F2 vs. F3, P=0.0177; F3 vs. cirrhosis, P<0.0001. The areas under the receiver operating characteristic curves of the time interval were 0.94, 0.96 and 0.98 for the diagnosis of marked fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis respectively. Conclusions: Contrast-enhanced US with Sonazoid™ may be a promising method for the indirect evaluation of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim was to examine the efficacy of contrast-enhanced ultrasound (US) with Sonazoid™ to demonstrate ultrasonically unrecognizable hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US-guided treatments. Methods: The subjects of this prospective study were 44 cirrhotic patients with 55 hypervascular lesions (12.7±4.5 mm) found by contrast-enhanced computed tomography but unrecognized by non-contrast US. Contrast-enhanced US was performed to demonstrate these hepatic lesions after an intravenous injection of Sonazoid™ (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after injection) and the late phase (5–10 min after) were taken in the harmonic imaging mode under a low mechanical index (0.24–0.3). Results: Fifty-three lesions were demonstrated by contrast-enhanced US, 52 with positive enhancement in the early phase and 44 with negative enhancement in the late phase. Percutaneous US-guided treatments were successfully performed for 42 lesions (ethanol injection in 20 and radiofrequency ablation in 22) in 32 patients with reference to contrast-enhanced US findings. Six patients were treated by transarterial chemoembolization alone because they had more than three lesions in the liver. In the remaining seven lesions in six patients, six were diagnosed as non-HCC lesions: five with vascular abnormalities such as arterioportal or arteriovenous communication and the other one with benign lesion in alcoholic liver disease. These six lesions and one HCC lesion with severe liver damage were followed up without any treatment. Conclusions: As the detectability of ultrasonically unrecognizable hypervascular HCC improved by contrast-enhanced US with Sonazoid™, a wider application of percutaneous US-guided treatments may be possible. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC). Materials and methods: This prospective study enrolled 10 patients with histologically proven HCC (14.4–39.0mm, 26.1±7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22–0.25) during the vascular phase (agent injection to 1min) and late phase (15min) following the injection of Sonazoid™ (0.0075ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced. Results: Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules. Conclusion: Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid. [Copyright &y& Elsevier]

Abstract: Objective: To examine the potential utility of 3D-reconstructed sonograms to distinguish cirrhotic from non-cirrhotic livers by demonstrating hepatic surface characteristics. Materials and methods: A preliminary phantom study was performed to examine the potential resolution of 3D images, recognizing surface irregularities as a difference in height. In a prospective clinical study of 31 consecutive patients with ascites (21 cirrhosis, 10 non-cirrhosis), liver volume data were acquired by transabdominal mechanical scanning. The hepatic surface features of cirrhotic and non-cirrhotic patients were compared by 2 independent reviewers. Intra- and inter-operator/reviewer agreements were also examined. Results: The phantom study revealed that 0.4mm was the minimum recognizable difference in height on the 3D sonograms. The hepatic surface image was successfully visualized in 74% patients (23/31). Success depended on the amount of ascites; visualization was 100% with ascites of 10mm or more between the hepatic surface and abdominal wall. The images showed irregularity of the hepatic surface in all cirrhotic patients. The surface appearance was confirmed as being very similar in 3 patients who had both 3D sonogram and liver resection for transplantation. The ability to distinguish cirrhotic liver from non-cirrhotic liver improved with the use of combination of 2D- and 3D-imaging versus 2D-imaging alone (sensitivity, p =0.02; accuracy, p =0.02) or 3D-imaging alone (sensitivity, p =0.03). Intra-/inter-operator and inter-reviewer agreement were excellent (κ =1.0). Conclusion: 3D-based sonographic visualization of the hepatic surface showed high reliability and reproducibility, acting as a virtual laparoscopy method, and the technique has the potential to improve the diagnosis of cirrhosis. [Copyright &y& Elsevier]

Abstract: This study aimed to characterize the features of heterogeneous staining in the liver after injection of perflubutane microbubble agent (SonazoidTM, 0.0075 mL/kg). Digitized hepatic contrast sonograms from 906 subjects were reviewed to assess time-related changes in heterogeneous staining and the possible association between this effect and the clinical backgrounds was analyzed. Heterogeneous staining was found in seven subjects (0.77%) on 15-min phase sonograms. The staining initially appeared as hyper-enhanced circular spots in the liver 10 min or later after the agent injection. The number of spots increased gradually with unequally-spaced distribution. Although the staining pattern did not improve during the examination, there were no abnormal findings in vital signs or symptoms on the day and blood test results or sonograms on the following day. Heterogeneous staining is a side effect that impedes ultrasound examination. However, at present, the precise causes and underlying mechanisms of this event are unknown. [Copyright &y& Elsevier]

Objective: The aim of this study was to determine the feasibility of using transabdominal three-dimensional (3D) colour Doppler ultrasound as a non-invasive tool to demonstrate and quantify gastric varices. Subjects and methods: A phantom study compared the 3D water flow volume data in a hose with the actual volume inside the hose at three different flow velocities. The prospective clinical study examined the reliability and reproducibility of 3D volume data for gastric varices (mild 28, moderate 26, large 8) in 62 patients. The 3D images were acquired using the colour Doppler with both convex and micro-convex probes. Results: The phantom study showed a 12.4–17.6% difference between the 3D data and the actual volume with no difference between the two types of probes or three velocities. The detectability of gastric varices was identical between the two probes (54/62, 87.1%). However, the scanning efficiency was significantly greater for the micro-convex probe (66.9±14.1%) than the convex probe (57.3±14%, p =0.012). Body mass index was the only factor that had a significant relationship with the detectability of varices. The mean volume (mL) of the 3D signal was 0.82±0.74 for mild varices, 5.48±3.84 for moderate varices, and 10.63±6.67 for large varices with significant differences between different grades. The intra-/inter-rater reliability was excellent. Conclusion: The method of 3D colour Doppler ultrasound is reliable and reproducible in the quantitative assessment of vascular volume and is applicable for grading gastric varices. This study may offer a practical usefulness for 3D ultrasonography as an alternative to endoscopy. [ABSTRACT FROM AUTHOR]