Sonazoid Contrast-enhanced Ultrasound Research Articles

A non-invasive predictive model based on multimodality ultrasonography images to differentiate malignant from benign focal liver lesions

We have developed a non-invasive predictive nomogram model that combines image features from Sonazoid contrast-enhanced ultrasound (SCEUS) and Sound touch elastography (STE) with clinical features for accurate differentiation of malignant from benign focal liver lesions (FLLs). This study ultimately encompassed 262 patients with FLLs from the First Hospital of Shanxi Medical University, covering the period from March 2020 to April 2023, and divided them into training set (n = 183) and test set (n = 79). Logistic regression analysis was used to identify independent indicators and develop a predictive model based on image features from SCEUS, STE, and clinical features. The area under the receiver operating characteristic (AUC) curve was determined to estimate the diagnostic performance of the nomogram with CEUS LI-RADS, and STE values. The C-index, calibration curve, and decision curve analysis (DCA) were further used for validation. Multivariate and LASSO logistic regression analyses identified that age, ALT, arterial phase hyperenhancement (APHE), enhancement level in the Kupffer phase, and Emean by STE were valuable predictors to distinguish malignant from benign lesions. The nomogram achieved AUCs of 0.988 and 0.978 in the training and test sets, respectively, outperforming the CEUS LI-RADS (0.754 and 0.824) and STE (0.909 and 0.923) alone. The C-index and calibration curve demonstrated that the nomogram offers high diagnostic accuracy with predicted values consistent with actual values. DCA indicated that the nomogram could increase the net benefit for patients. The predictive nomogram innovatively combining SCEUS, STE, and clinical features can effectively improve the diagnostic performance for focal liver lesions, which may help with individualized diagnosis and treatment in clinical practice.

Evaluation of Renal Masses Using Contrast-Enhanced Ultrasound with Sonovue and Sonazoid

ObjectiveTo explore the differences between SonoVue and Sonazoid contrast-enhanced ultrasound (CEUS) in evaluating enhancement features of renal masses and determine the diagnostic value of CEUS in clear cell renal cell carcinoma (ccRCC). MethodsA total of 57 eligible patients were enrolled and divided into the ccRCC, papillary renal cell carcinoma (pRCC), non-ccRCC and non-pRCC malignancy groups, and benign mass groups based on their postsurgical histopathologic diagnosis. The enhancement features of renal masses following SonoVue and Sonazoid CEUS in each group were analyzed. Diagnostic efficiencies of SonoVue and Sonazoid CEUS for ccRCC and non-ccRCC were determined. ResultsThere were no significant differences in the enhancement features of renal masses with SonoVue and Sonazoid imaging in the four groups (p > .05). Both SonoVue CEUS and Sonazoid CEUS showed good diagnostic performance for the differential diagnosis of ccRCC and non-ccRCC, with sensitivities of 88.6% and 85.7%, specificities of 76.5% and 88.2%, accuracies of 84.6% and 86.5%, positive predictive values of 88.6% and 93.8%, and negative predictive values of 76.5% and 75%, respectively. There were no statistically significant differences in any of the diagnostic performance indices between the two methods (p > .05). ConclusionThe CEUS features of SonoVue and Sonazoid in evaluating renal masses were similar in the vascular phase. Both SonoVue and Sonazoid CEUS showed good diagnostic performance for the differential diagnosis of ccRCC and non-ccRCC.

Perfluorobutane-Enhanced CEUS in Intrahepatic Cholangiocarcinoma: Correlating Imaging Features With Liver Backgrounds and Tumor Sizes

ObjectiveTo investigate Sonazoid contrast-enhanced ultrasound (CEUS) features of intrahepatic cholangiocarcinoma (ICC) based on liver backgrounds and tumor sizes. MethodsA retrospective analysis was conducted on patients with histopathologically diagnosed ICC at two centers. Patients underwent Sonazoid CEUS examination at a dose of 0.0165 mL/kg before surgery or biopsy. Continuous imaging was recorded for the first 70 s, followed by intermittent scanning every 15–20 s for 5 min, with a Kupffer phase captured after an 8-min delay. Patients were categorized by liver backgrounds and tumor sizes. Two ultrasound experts evaluated the enhancement patterns of ICCAs during the arterial, portal, delayed, and Kupffer phases according to current guidelines. ResultsFrom February 2019 to July 2022, a total of 85 ICC lesions were included. ICCs were categorized into normal liver (n = 24), chronic liver disease with fibrosis (n = 40), and cirrhosis (n = 21) groups based on different liver backgrounds, and into groups measuring ≤30 mm (n = 22), 31–50 mm (n = 32), and >50 mm (n = 31) based on tumor sizes. Most ICCs in liver fibrosis or liver cirrhosis tended to show non-rim enhancement in arterial phase (p = 0.022) and relatively later washout (39.9 ± 8.5 s vs. 39.7 ± 13.0 s) compared with those on a normal liver background (28.1 ± 5.6 s) (p < 0.001). Based on CEUS Liver Imaging Reporting and Data System, the diagnostic performance of LR-M criteria showed an accuracy of 100% in our high-risk populations. ICCs of ≤30 mm more commonly showed non-rim enhancement in arterial phase (p = 0.003) and relatively later washout (41.3 ± 12.5 s) compared with larger ICCs (p = 0.046). In the Kupffer phase, all ICCs showed marked washout with sharp margin delineation on Sonazoid CEUS, regardless of liver backgrounds and tumor sizes. ConclusionSonazoid CEUS features of ICCs differ according to different liver backgrounds and tumor sizes. Arterial phase non-rim enhancement and relatively later washout were more commonly observed in ICCs on liver fibrosis or cirrhosis background or smaller ICCs (≤30 mm).

Perfluorobutane (Sonazoid) Contrast-enhanced ultrasound to diagnose hepatocellular carcinoma: A systematic review and meta-analysis.

This meta-analysis aimed to assess the precision of Sonazoid contrast-enhanced ultrasound (CEUS) to distinguish hepatocellular carcinoma (HCC) from focal liver lesions (FLLs). The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched and checked for studies using Sonazoid CEUS to characterize HCC. A comprehensive meta-analysis was conducted, involving data pooling, subgroup analyses, meta-regression, and investigation of publication bias. The meta-analysis included fourteen studies. The overall diagnostic accuracy for characterizing HCC was as follows (all ranges show the 95% confidence interval): pooled sensitivity of 0.87 (0.80-0.92), pooled specificity of 0.95 (0.91-0.97), and a diagnostic odds ratio of 121 (61-241). The overall weighted area under the curve was 0.97 (0.95-0.98). The pooled sensitivity, specificity, and diagnostic odds ratio for Sonazoid and Sonovue were 0.75 (0.63- 0.84), 0.97 (0.86-0.99), 82 (15-445); and 0.64 (0.51-0.76), 0.98 (0.91-0.99), 72 (17-311), respectively. The sources of heterogeneity were identified as the study location, prevailing risk factor, reference diagnosis standard, criteria of Sonazoid CUES, and the proportion of cases of HCC. We observed no potential publication bias. Sonazoid CEUS is efficient to distinguish HCC from FLLs, with good sensitivity and specificity. It is comparable to Sonovue CEUS to diagnose HCC.

Percutaneous ablation of colorectal liver metastases: a comparison between the outcomes of grayscale US guidance and Sonazoid CEUS Kupffer phase guidance using propensity score matching

Purpose To assess the utility of Sonazoid contrast-enhanced ultrasound (CEUS) for guiding percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs). Materials and Methods The medical records of patients who had undergone ultrasound (US)-guided percutaneous MWA between July 2020 and June 2022, were reviewed. Propensity score matching (PSM) with a ratio of 1:1 was used to balance the potential bias between the grayscale US-guided and Sonazoid CEUS-guided groups. Local tumor progression (LTP), intrahepatic recurrence (IR), and complication rates were compared between the two groups. Results Of 252 patients enrolled, 247 achieved complete ablation, and the technical effectiveness was 98.0% (247/252). Of these 247 patients, 158 were in the grayscale US-guided group and 89 in the Sonazoid CEUS-guided group. The median follow-up period was 14.6 months. After PSM, there were no significant differences in LTP, IR, or complication rates between the two groups (p = 0.100, p = 0.511, p > 0.99, respectively). Multivariate analysis identified tumor size ≥ 3 cm (hazard ratio [HR], 7.945; 95% CI, 2.591-24.370; p < 0.001), perivascular (HR, 2.331; 95% CI, 1.068-5.087; p = 0.034), and tumor depth > 8 cm (HR, 3.194; 95% CI, 1.439-7.091; p = 0.004) as significant factors associated with LTP. For tumors with poor vision on grayscale US, Sonazoid CEUS-guided ablation achieved a better LTP rate than grayscale US-guided ablation (3.7% vs.14.8%, p = 0.032). Conclusion For tumors with poor vision on grayscale US, Sonazoid CEUS guidance is recommended for better local tumor control.

Diagnosis of hepatocellular carcinoma using Sonazoid: a comprehensive review.

Sonazoid contrast-enhanced ultrasonography (CEUS) is a promising technique for the detection and diagnosis of focal liver lesions, particularly hepatocellular carcinoma (HCC). Recently, a collaborative effort between the Korean Society of Radiology and Korean Society of Abdominal Radiology resulted in the publication of guidelines for diagnosing HCC using Sonazoid CEUS. These guidelines propose specific criteria for identifying HCC based on the imaging characteristics observed during Sonazoid CEUS. The suggested diagnostic criteria include nonrim arterial phase hyperenhancement, and the presence of late and mild washout, or Kupffer phase washout under the premise that the early or marked washout should not occur during the portal venous phase. These criteria aim to improve the accuracy of HCC diagnosis using Sonazoid CEUS. This review offers a comprehensive overview of Sonazoid CEUS in the context of HCC diagnosis. It covers the fundamental principles of Sonazoid CEUS and its clinical applications, and introduces the recently published guidelines. By providing a summary of this emerging technique, this review contributes to a better understanding of the potential role of Sonazoid CEUS for diagnosing HCC.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines from the Korean Society of Radiology and the Korean Society of Abdominal Radiology

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Nomogram based on Sonazoid contrast-enhanced ultrasound to differentiate intrahepatic cholangiocarcinoma and poorly differentiated hepatocellular carcinoma: a prospective multicenter study.

The aim of this study was to develop a predictive model based on Sonazoid contrast-enhanced ultrasound (SCEUS) and clinical features to discriminate poorly differentiated hepatocellular carcinoma (P-HCC) from intrahepatic cholangiocarcinoma (ICC). Forty-one ICC and forty-nine P-HCC patients were enrolled in this study. The CEUS LI-RADS category was assigned according to CEUS LI-RADS version 2017. Based on SCEUS and clinical features, a predicated model was established. Multivariate logistic regression analysis and LASSO logistic regression were used to identify the most valuable features, 400 times repeated 3-fold cross-validation was performed on the nomogram model and the model performance was determined by its discrimination, calibration, and clinical usefulness. Multivariate logistic regression and LASSO logistic regression indicated that age (>51 y), viral hepatitis (No), AFP level (≤ 20 µg/L), washout time (≤ 45 s), and enhancement level in the Kupffer phase (Defect) were valuable predictors related to ICC. The area under the receiver operating characteristic (AUC) of the nomogram was 0.930 (95% CI: 0.856-0.973), much higher than the subjective assessment by the sonographers and CEUS LI-RADS categories. The calibration curve showed that the predicted incidence was more consistent with the actual incidence of ICC, and 400 times repeated 3-fold cross-validation revealed good discrimination with a mean AUC of 0.851. Decision curve analysis showed that the nomogram could increase the net benefit for patients. The nomogram based on SCEUS and clinical features can effectively differentiate P-HCC from ICC.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology.

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

New Ultrasonographic Techniques to Differentiate Hepatic Masses: Contrast-Enhanced Ultrasound and Super-Resolution Ultrasound

Contrast-enhanced ultrasound (CEUS) and super-resolution ultrasound (US) are novel ultrasound technologies for differentiating hepatic masses including hepatocellular carcinoma (HCC). Kupffer-phase imaging on Sonazoid CEUS can increase the diagnostic sensitivity for HCC, and facilitates early identification and treatment of HCC. On the other hand, super-resolution US can depict intratumoral vascularity without contrast enhancement, and its diagnostic performance for identifying the spoke-wheel pattern of focal nodular hyperplasia is equivalent to that of CEUS.

Contrast-Enhanced Ultrasound With SonoVue and Sonazoid for the Diagnosis of Colorectal Liver Metastasis After Chemotherapy.

To compare the diagnostic efficacy of SonoVue and Sonazoid contrast-enhanced ultrasound (CEUS) in correctly detecting and characterizing colorectal liver metastasis (CRLM) after chemotherapy. Patients with CRLMs treated with chemotherapy and subsequently scheduled for hepatic resection were prospectively enrolled from April 2020 to January 2021. Lesions detected by SonoVue or Sonazoid CEUS were recorded as and characterized as metastases or non-metastatic lesions respectively. Histopathology or intraoperative ultrasound with MRI were the reference standard. A total of 348 focal liver lesions in 42 patients were investigated, including 297 CRLMs and 51 non-metastatic lesions. SonoVue showed significantly higher diagnostic accuracy (64.7% versus 54.0%; P<.001) and sensitivity (63.3% versus 50.5%; P<.001) in the diagnosis of CRLMs than Sonazoid, both methods presented with similar specificity (72.5% versus 74.5%; P=1.0). Forty metastases appeared non-hypoenhancing (hyperenhancing or isoenhancing) in the late phase and postvascular phase of Sonazoid CEUS and were mischaracterized as benign lesions. SonoVue performed significantly better than Sonazoid in the diagnosis of CRLMs after chemotherapy.

Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma based on kupffer phase radiomics features of sonazoid contrast-enhanced ultrasound (SCEUS): A prospective study.

To establish and to evaluate a machine learning radiomics model based on grayscale and Sonazoid contrast enhanced ultrasound images for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. 100 cases of histopathological confirmed HCC lesions were prospectively included. Regions of interest were segmented on both grayscale and Kupffer phase of Sonazoid contrast enhanced (CEUS) images. Radiomic features were extracted from tumor region and region containing 5 mm of peritumoral liver tissues. Maximum relevance minimum redundancy (MRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) were used for feature selection and Support Vector Machine (SVM) classifier was trained for radiomic signature calculation. Radiomic signatures were incorporated with clinical variables using univariate-multivariate logistic regression for the final prediction of MVI. Receiver operating characteristic curves, calibration curves and decision curve analysis were used to evaluate model's predictive performance of MVI. Age were the only clinical variable significantly associated with MVI. Radiomic signature derived from Kupffer phase images of peritumoral liver tissues (kupfferPT) displayed a significantly better performance with an area under the receiver operating characteristic curve (AUROC) of 0.800 (95% confidence interval: 0.667, 0.834), the final prediction model using age and kupfferPT achieved an AUROC of 0.804 (95% CI: 0.723, 0.878), accuracy of 75.0%, sensitivity of 87.5% and specificity of 69.1%. Radiomic model based on Kupffer phase ultrasound images of tissue adjacent to HCC lesions showed an observable better predictive value compared to grayscale images and has potential value to facilitate preoperative identification of HCC patients at higher risk of MVI.

Dynamic Contrast-Enhanced Ultrasonography with Sonazoid for Diagnosis of Microvascular Invasion in Hepatocellular Carcinoma.

The aim of the present study was to investigate the imaging features observed in pre-operative Sonazoid contrast-enhanced ultrasound (SZ-CEUS) and the correlations with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. In this single-center retrospective study, 31 patients with surgically and histopathologically confirmed HCC lesions were included. Patients were classified according to the presence of MVI into the MVI-positive group (n=15) and MVI-negative group (n=16). The CEUS examinations were performed within 2 or 3 d before surgery. Features, including tumor necrosis and ultrasound contrast agent (UCA) distribution characteristics in the arterial phase (AP), tumor types (single nodular [SN] or non-single nodular [non-SN]) in the post-vascular phase (PVP), wash-in time, wash-in slope, time to peak (TTP) and peak intensity (PI), were assessed. Univariate analysis revealed statistically significant differences between the two groups with respect to tumor necrosis (p=0.002), inhomogeneous distribution of contrast agent in the AP (p=0.001) and non-SN type in the PVP (p < 0.001). There was no significant difference in the quantitative parameters. Multivariate analysis revealed that non-SN type in the PVP was a significant independent risk factor for MVI of HCC (odds ratio=30.51, 95% confidence interval [CI]: 2.335-398.731, p=0.009). The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.873, 93.3%, 81.3%, 82.4% and 92.9%, respectively. Thus, SZ-CEUS can provide useful information for the diagnosis of MVI in HCC.

Comparison of Sonazoid contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid MRI for the histological diagnosis of hepatocellular carcinoma.

This study aimed to compare the value of Sonazoid contrast-enhanced ultrasound (SCEUS) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) for histological grading diagnosis, especially for early hepatocellular carcinoma (eHCC). A total of 163 histopathologically confirmed HCC lesions were retrospectively collected, including 71 eHCCs (27 hypervascular, 44 non-hypervascular) and 92 advanced HCCs (adHCC) (73 hypervascular, 19 non-hypervascular). We performed SCEUS to evaluate the lesions' vascularity during the portal phase (PP) and the echogenicity during the post-vascular phase (PVP). EOB-MRI was used to determine the signal intensity between lesions and the surrounding liver parenchyma on unenhanced T1-weighted images (pre-contrast ratio) in the hepatobiliary phase (HBP) (post-contrast ratio). For the PP and PVP of SCEUS (for all lesions), the pre-and post-contrast ratios of EOB-MRI (for all hypervascular lesions) showed statistical differences in the diagnosis of some (but not all) histological grades. For the diagnosis of eHCC, isoechogenicity in the PVP achieved the best diagnostic efficacy [area under the receiver operating characteristic curve (AUC) =0.892]. Whether used independently or in a combination of any form, all indicators failed to produce a higher diagnostic efficacy than PVP. Post- (≥0.610) and pre-contrast ratios (≥0.981) yielded acceptable diagnostic efficacy, with, respectively, accuracy levels of 69.3% and 75.5% and AUC values of 0.719 and 0.736. For eHCC diagnosis, the post-contrast ratio (≥0.625) and combined diagnosis using pre- (≥0.907) and post-contrast ratios (≥0.609) revealed the highest sensitivity (92.6%) for hypervascular lesions and perfect specificity (100%) for non-hypervascular lesions. Unenhanced T1-weighted images and the HBP of EOB-MRI [regardless of the vascularity in the arterial phase (AP)], and the PP and PVP of SCEUS showed their value in the histological grading diagnosis of HCC. In particular, isoechogenicity in the PVP may have promising diagnostic utility for eHCC.

A case of hemorrhagic hepatic cyst presenting with mobility of the papillary septum and continuous hyperenhancement by Sonazoid contrast-enhanced ultrasonography

68歳女性．右膝蓋骨骨折のため近医整形外科入院中，腹部CTで肝右葉に12 cm大の腫瘍性病変を認め当院に入院した．腹部超音波検査（US）で可動性を呈する乳頭状隔壁を認めた．乳頭状隔壁は，MRIでも認めたがCTでは描出されず所見が乖離していた．Sonazoid造影超音波検査（Sonazoid CEUS）では，壁在結節の造影効果が持続しCA19-9 198.9 U/mlと上昇しており，外科的切除術を施行した．囊胞性腫瘤の内部は，フィブリン，コレステリン結晶を含んだ茶褐色の混濁した漿液が貯留し囊胞壁は不均一な線維性硬化を認め出血性肝囊胞と診断した．術後に画像所見を見直すと出血性肝囊胞に特徴的な所見である，USで可動性を呈するがCTでは描出されない乳頭状隔壁を認めた．さらに，Sonazoid CEUSでの壁在結節の造影効果の持続がよく観察されており同疾患の診断に有用な所見と考えられたため報告する．

Comparison Between SonoVue and Sonazoid Contrast-Enhanced Ultrasound in Characterization of Focal Nodular Hyperplasia Smaller Than 3 cm.

This study aimed to compare the diagnostic efficacy of contrast-enhanced ultrasound (CEUS), including SonoVue (SV; sulfur hexafluoride; Bracco SpA, Milan, Italy) and Sonazoid (SZ; perflubutane; GE Healthcare, Oslo, Norway), and explore the differences between them in the characterization of CEUS features in focal nodular hyperplasia (FNH) smaller than 3 cm. This retrospective study included 31 lesions smaller than 3 cm diagnosed as FNH by CEUS between April 2019 and November 2019. Nine patients underwent SZ CEUS examinations, and 22 patients underwent SV CEUS examinations; all of them were confirmed by pathologic examinations or 2 other kinds of CEUS methods. We compared the CEUS features between SZ and SV in different phases, including arterial, portal venous, delayed, and Kupffer (SZ) phases. Twenty-eight lesions were eventually diagnosed as FNH; 3 were misdiagnosed as FNH by SV CEUS. The overall diagnostic accuracy of CEUS including SZ and SV was 90.3% (28 of 31). No significant difference was found (P > .05) for the positive predictive value. Likewise, no significant difference in depicting centrifugal filling (9 of 9 versus 19 of 19), spoke wheel artery (6 of 9 versus 8 of 19), or feeding artery (2 of 9 versus 10 of 19) features was found between the contrast agents; However, SZ was significantly better at depicting the presence of a central scar than SV (5 of 9 versus 3 of 19; P=.030). Misdiagnosed cases are discussed in detail. Contrast-enhanced ultrasound enables an accurate diagnosis in FNH smaller than 3 cm. Sonazoid CEUS and SV CEUS were comparable in diagnosing small FNH, and both agents were highly capable of depicting the centrifugal filling dynamic process of FNH smaller than 3 cm. Sonazoid CEUS might be better than SV CEUS at depicting a central scar.

Early hemodynamics of hepatocellular carcinoma using contrast-enhanced ultrasound with Sonazoid: focus on the pure arterial and early portal phases.

To clarify the early hemodynamics of hepatocellular carcinoma (HCC), we defined the early portal phase of contrast-enhanced ultrasound (CEUS) and examined the reliability of this modality for determining HCC differentiation. Starting in 2007, we performed Sonazoid CEUS in 146 pathologically confirmed hepatic nodules; 118 HCC (8 poorly [Pd], 73 moderately [Md] and 37 well-differentiated [Wd]) and 28 benign nodules. We focused on the pure arterial and early portal phases up to 45 seconds after Sonazoid injection, and then the subsequent phase up to 30 minutes. We calculated covariance-adjusted sensitivities for nodule enhancement combinations of these three phases. Nodule enhancements were divided into hypo, iso and hyper. A positive predictive value of 100% was obtained for the following patterns: iso-iso-hypo, hypo-iso-iso, and hypo-hypo-hypo for Wd, hyper-iso-hypo and hyper-hypo-hypo for Md, hypo-hyper-hypo for Pd, and hyper-hyper-hyper for benign nodules. In Wd HCC (early HCC), there were seven enhancement patterns, thought to be characterized by various hemodynamic changes from early to advanced HCC. Two patterns allowing a diagnosis of Wd HCC were hypo in the pure arterial phase. Subsequent iso-enhancement in the early portal phase indicated a portal blood supply. Decreased enhancement in the early portal phase allows a diagnosis of Md HCC. However, gradual enhancement observed from the pure arterial to the early portal phase allows a diagnosis of Pd HCC. Therefore, even in the early portal phase, hemodynamic changes were visible not only in Wd but also in Md and Pd HCC. In conclusion, with division of the early phase hemodynamics into pure arterial and early portal phases, CEUS can provide information useful for determining the likely degree of HCC differentiation and for distinguishing early stage HCC from benign nodules.

Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma.

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

Quantitative Contrast-Enhanced Ultrasound by Sonazoid in the Early Diagnosis of Biliary Atresia: An Experimental Study of Rats With Bile Duct Ligation

We aimed to investigate the feasibility of quantitative Sonazoid contrast-enhanced ultrasound (CEUS) in the diagnosis of biliary atresia (BA) at an early disease stage. First, liver tissue from 10 patients with BA and 10 patients with infantile hepatitis syndrome (IHS) was immunostained with cluster of differentiation 68 (CD68) to compare Kupffer cell counts. Then, quantitative Sonazoid CEUS was performed to evaluate the hyperplasia of the artery branches during the artery phase and changes in Kupffer cell counts during the Kupffer phase in a rat model of BA (common bile duct ligation). Based on our results, liver enhancement from Kupffer cells in BA patients was significantly higher than that in IHS patients (p = 0.026 < 0.05). Furthermore, quantitative CEUS showed that the liver enhancement intensity of rats with bile duct ligation was substantially greater than that of rats without bile duct ligation during the artery phase 3 d post-operation and the Kupffer phase 5 d post-operation. The increased enhancement intensity in the Kupffer phase was in agreement with the increase in Kupffer cell counts in pathologic staining (18/20, 90%). In conclusion, quantitative Sonazoid CEUS can detect the hyperplasia of artery branches in artery phase and the increase of Kupffer cells in Kupffer phase in the liver of BA rats at an early disease stage. Therefore, Sonazoid CEUS could potentially be a valuable non-invasive alternative for the diagnosis of BA.

Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature.

The present study reports the case of a 68-year-old male patient who presented to Tokyo Rosai Hospital for the treatment of alcoholic liver disease. A high density was observed in liver segment S2, while a tumor, 30 mm in size, exhibiting a low density was observed in the delayed phase upon contrast-enhanced computed tomography (CT), which was performed prior to admission. The tumor appeared slightly poorly defined upon abdominal ultrasound and was observed as a 30 mm low-echoic nodule that was internally heterogeneous. A 5-mm thick contrast enhancement effect was observed in the tumor border in the vascular phase on Sonazoid contrast-enhanced ultrasonography, while a defect in the entire tumor was observed in the post-vascular phase. Dysphagia had commenced three months prior to presentation and a weight loss of ~3 kg was observed. Therefore, the patient was admitted to Tokyo Rosai Hospital due to the presence of a hepatic tumor, and to undergo a close inspection of the cause of the tumor. Upon close inspection, it was determined that the weight loss and aphagia were caused by progressive bulbar paralysis. A contrast-enhanced CT was performed on post-admission day 29 as a follow-up regarding the hepatic tumor. As a result, although no change in the tumor size was observed, the contrast enhancement in the tumor borderline had disappeared. Necrosis of the tumor was considered. However, as viable persistence of the malignant tumor could not be excluded, a hepatic left lobe excision was performed. The patient was diagnosed with hepatocellular carcinoma (HCC) based on the morphology of the cellular necrosis. In addition, occlusion due to thrombus was observed within the blood vessels passing inside the fibrous capsule. It was hypothesized that the formation of a thick fibrous capsule and occlusion due to thrombus in the feeding vessel were possibly involved as the cause of complete spontaneous necrosis. Written informed consent was obtained from the patient.