Sonazoid-enhanced Ultrasonography Research Articles

Diagnostic Test Accuracy of Contrast-Enhanced Ultrasound With Sonazoid for Assessment of Focal Liver Lesions: A Systematic Review and Meta-Analysis.

This meta-analysis examined the diagnostic accuracy of Sonazoid-enhanced ultrasonography (SZ-CEUS) in discriminating malignant from benign focal liver lesions (FLLs) and HCC from non-HCC FLLs. Finding relevant studies required a rigorous PubMed, EMBASE, and other database search. To distinguish malignant from benign FLLs, SZ-CEUS had a pooled sensitivity of 94% (95% CI: 0.91-0.95) and specificity of 84% (95%: 0.78-0.89). HCC distinction had 83% sensitivity and 96% specificity (95% CI: 0.80-0.85 and 0.95-0.97). SZ-CEUS accurately distinguishes malignant from benign FLLs and HCC from non-HCC lesions, especially smaller HCC lesions.

Value of Sonazoid-enhanced ultrasonography in characterizing indeterminate focal liver lesions on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma.

To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.

Sonazoid-enhanced ultrasonography for noninvasive imaging diagnosis of hepatocellular carcinoma: special emphasis on the 2022 KLCA-NCC guideline.

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

Second-line Sonazoid-enhanced ultrasonography for Liver Imaging Reporting and Data System category 3 and 4 on gadoxetate-enhanced magnetic resonance imaging.

PurposeThis study investigated the utility of second-line contrast-enhanced ultrasonography (CEUS) using Sonazoid in Liver Imaging Reporting and Data System category 3 (LR-3) and 4 (LR-4) observations on gadoxetate-enhanced magnetic resonance imaging (MRI).MethodsThis retrospective study included LR-3 or LR-4 observations on gadoxetate-enhanced MRI subsequently evaluated with CEUS from 2013 to 2017. The presence of MRI features, CEUS-arterial phase hyperenhancement (CEUS-APHE), and Kupffer phase defect (KPD) was evaluated. Multivariable logistic regression analysis was performed to identify significant imaging features associated with the diagnosis of hepatocellular carcinoma (HCC). The optimal diagnostic criteria were investigated using the McNemar test.ResultsIn total, 104 patients with 104 observations (63 HCCs) were included. The presence of both CEUS-APHE and KPD on CEUS enabled the additional detection of 42.3% (11/26) of LR-3 HCCs and 78.4% (29/37) of LR-4 HCCs. Transitional phase (TP) hypointensity (adjusted odds ratio [OR], 10.59; P<0.001), restricted diffusion (adjusted OR, 7.55; P=0.004), and KPD (adjusted OR, 7.16; P=0.003) were significant imaging features for HCC diagnosis. The presence of at least two significant imaging features was optimal for HCC diagnosis (sensitivity, specificity, and accuracy: 88.9%, 78.1%, and 84.6%, respectively), with significantly higher sensitivity than the presence of both CEUS-APHE and KPD (sensitivity, specificity, and accuracy: 63.5% [P=0.001], 92.7% [P=0.077], and 75.0% [P=0.089], respectively).ConclusionThe combined interpretation of gadoxetate-enhanced MRI and second-line CEUS using Sonazoid, focusing on TP hypointensity, restricted diffusion, and KPD, may be optimal for further characterizing LR-3 and LR-4 observations.

Sonazoid-enhanced ultrasonography: comparison with CT/MRI Liver Imaging Reporting and Data System in patients with suspected hepatocellular carcinoma.

PurposeThe aim of this study was to evaluate the association of contrast-enhanced ultrasound (CEUS) features using Sonazoid for liver nodules with Liver Imaging Reporting and Data System (LI-RADS) categories and to identify the usefulness of Kupffer-phase images.MethodsThis retrospective study was conducted in 203 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS with Sonazoid from 2013 to 2016. Nodule enhancement in the arterial, portal venous, late, and Kupffer phases; CEUS LI-RADS major features; and Kupffer-phase defects were evaluated. According to the computed tomography/magnetic resonance imaging (CT/MRI) LI-RADS v2018, all nodules were assigned an LR category (n=4/33/99/67 for LR-M/3/4/5) and comparisons across LR categories were made. We defined modified CEUS LI-RADS as using Kupffer-phase defects as an alternative to late and mild washout in CEUS LI-RADS and compared the diagnostic performance for HCC.ResultsOn CEUS of 203 nodules, 89.6% of CT/MRI LR-5 and 85.9% of LR-4 nodules showed hyperenhancement in the arterial phase, while 57.6% of LR-3 nodules showed hyperenhancement. Among the CT/MRI LR-5 nodules that showed arterial phase hyperenhancement or isoenhancement, 59.7% showed hypoenhancing changes from the portal venous phase, 23.9% from the late phase, and 13.4% additionally in the Kupffer phase. The modified CEUS LI-RADS showed higher sensitivity than CEUS LI-RADS (83.2% vs. 74.2%, P=0.008) without compromising specificity (63.6% vs. 69.7%, P=0.500).ConclusionThe Kupffer phase best shows hypoenhancing changes in LR-5 lesions and is expected to improve the sensitivity for HCC in high-risk patients.

Value of contrast-enhanced sonography of small hepatocellular carcinoma with sonazoid prior to radiofrequency ablation.

We aimed to determine the value of contrast-enhanced sonography (CEUS) with Sonazoid prior to percutaneous radiofrequency ablation (RFA) of small (<3 cm) hepatocellular carcinoma (HCC). This prospective study was approved by our institutional review board and informed consent was obtained. The following criteria were used for study enrollment: (1) cirrhotic patients with HCCs found by contrast-enhanced CT or Gd-EOB-DTPA-enhanced MRI; (2) a single HCC <3 cm in longest diameter or multinodular HCCs (<3) with each tumor <3 cm in longest diameter; and (3) indeterminate identification of the index tumor from the surrounding cirrhosis-related pseudolesions on conventional US. Percutaneous RFA was performed under the guidance of CEUS with Sonazoid. The value of CEUS in index tumor detection and targeting was compared with that of concurrently performed conventional US. A total of 38 patients with 43 HCCs (mean size, 1.6 cm; range, 0.5-2.9 cm) were enrolled. The vascular phase of Sonazoid-enhanced ultrasonography showed good tumor enhancement in 30/43 HCCs (70%). The Kupffer phase increased lesion conspicuity and operator's diagnostic confidence in 29 patients with 31 HCCs (31/43, 72%) compared with conventional US. CEUS with Sonazoid is useful for detection and targeting of small HCC prior to RFA. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:383-390, 2017.

Sonazoid-Enhanced Ultrasonography Guidance Improves the Quality of Pathological Diagnosis in the Biopsy of Focal Hepatic Lesions

Contrast-enhanced ultrasonography (US) using second-generation contrast agent Sonazoid has improved the detection and characterization of focal hepatic lesions. We evaluated the utility of Sonazoid-enhanced ultrasonography (SEUS) in guiding percutaneous biopsy of focal hepatic lesions by comparing accuracy of histopathological diagnosis between B-mode US and SEUS guidance. This retrospective study included 140 focal hepatic lesions in 127 patients (mean age; 63.6 years) referred for US-guided percutaneous biopsy between April 2012 and September 2016. The diagnostic accuracy of the biopsy was defined as the percentage of the total number of lesions clearly diagnosed at the initial biopsy. A case was considered a technical failure when pathological results failed to specifically indicate final diagnosis owing to insufficient material or when pathological results changed from benign to malignant by re-biopsy. Among 140 focal hepatic lesions, 57 lesions underwent biopsy with B-mode US guidance while 83 received SEUS guidance. Patient characteristics (sex, age, lesion location and diameter, and reasons for biopsy) did not differ significantly between groups. Diagnostic accuracy was significantly higher under SEUS guidance than B-mode US guidance (91.6% vs. 75.4%, respectively; p < 0.05). When biopsies were performed to diagnose or rule out malignancy in indeterminate focal hepatic lesions, diagnostic accuracy was also significantly higher under SEUS guidance than B-mode US guidance (100% vs. 70.8%, respectively; p < 0.05). SEUS guidance resulted in a significantly higher rate of successful single-puncture attempts during biopsy procedures than B-mode US guidance (53.0% vs. 35.1%, respectively; p < 0.05). SEUS guidance improves the accuracy of hepatic tumor biopsy pathological diagnosis compared to B-mode US guidance. SEUS guidance is recommended for more accurate localization of suitable hepatic lesion biopsy areas since it increases conspicuity and differentiates viable area from denaturalization or necrosis.

CD68-Positive Cells in Hepatic Angiomyolipoma

Four resected specimens of hepatic angiomyolipoma in which uptake of Sonazoid was observed in the postvascular phase of Sonazoid-enhanced ultrasonography were analyzed. Macrophage localization in the tumor was revealed pathologically by immunohistochemical staining for CD68. CD68-positive cells were observed in the tumor in all cases. The density of CD68-positive cells was 100/mm², and the ratio of CD68-positive cell density in the tumor to that in the surrounding parenchyma was 32-171%. These results suggested that the uptake of the contrast agent Sonazoid was related to the density of CD68-positive cells.

Sonazoid-enhanced ultrasonography guidance improves the quality of pathological diagnosis in the biopsy of focal hepatic lesions

Contrast-enhanced ultrasonography (US) has improved the detection and characterization of focal hepatic lesions. Recently, the importance of obtaining high-quality samples in the biopsy of hepatic lesions has been increasing not only in the field of pathological diagnosis but also in molecular analysis for predicting the effectiveness of anticancer agents and molecular targeted drugs. We evaluated the utility of Sonazoid-enhanced ultrasonography (SEUS) in guiding percutaneous biopsy of focal hepatic lesions by comparing the results of histopathological diagnosis between B-mode US and SEUS guidance. This retrospective study examined 121 focal hepatic lesions in 108 patients (mean age: 63.8 years) referred for US-guided percutaneous biopsy. The technical success rate was defined as the percentage of the lesions diagnosed clearly at the initial biopsy. Among 121 lesions, 56 lesions were subjected to biopsy with B-mode US guidance whereas 65 were subjected to SEUS guidance. The technical success rate was significantly higher under SEUS guidance than under B-mode US guidance (92.3 vs. 76.8%, respectively, P<0.05). When biopsies were performed to diagnose or rule out malignancy in indeterminate lesions, the technical success rate was also significantly higher under SEUS guidance than under B-mode US guidance (100 vs. 73.9%, respectively, P<0.05). SEUS guidance resulted in a significantly higher rate of successful single-puncture attempts compared with B-mode US guidance (55.4 vs. 35.7%, respectively, P<0.05). SEUS guidance is recommended for more accurate localization of suitable hepatic lesion biopsy areas as it increases conspicuity and differentiates viable areas from denaturalization or necrosis.

Diagnosis of an intrapancreatic accessory spleen by sonazoid-enhanced ultrasonography

Diagnosis of an intrapancreatic accessory spleen by sonazoid-enhanced ultrasonography

ソナゾイド造影超音波で造影剤の残存を認めた肝血管筋脂肪腫におけるCD68陽性細胞の腫瘍内局在について

We investigated four resected cases of hepatic angiomyolipoma observed by residual contrast agent in the post vascular phase of Sonazoid-enhanced ultrasonography. In this study, localization of macrophages in the tumor was examined pathologically using immunostaining for CD68. CD68-positive cells were revealed in the tumor in all cases. The density of CD68-positive cells was >100/mm2, and the ratio of the density compared with the surrounding parenchyma was >30%. We concluded that the remaining contrast agent was related to the density of CD68-positive cells.

Effect of obstructive jaundice on hepatic hemodynamics: use of Sonazoid-enhanced ultrasonography in a prospective study of the blood flow balance between the hepatic portal vein and hepatic artery.

To prospectively clarify the effects of obstructive jaundice (OJ) on hepatic hemodynamics using contrast-enhanced ultrasonography (US). Subjects comprised 14 patients admitted to our hospital for OJ between April 2013 and March 2014. Contrast-enhanced US was performed using the LOGIQ E9 ultrasound device during the jaundice phase, before biliary drainage, and again after improvement of jaundice. After injecting the Sonazoid contrast agent, contrast dynamics were recorded in the right kidney and liver segments 5 or 6. Prototype software was used to calculate mean arrival time (AT) of the contrast agent in the liver parenchyma. Statistical analysis was performed to compare the mean AT in the jaundice and improved jaundice phases. We were unable to follow up three of the 14 patients after biliary drainage; thus, we included 11 patients for further analysis. The mean AT of the contrast agent was 2.0 ± 1.8 and 6.1 ± 2.3 s in the jaundice and improved jaundice phases, respectively, showing significantly shorter AT in the jaundice phase (p = 0.0033). Our findings indicate that OJ may influence the blood flow balance between the hepatic portal vein and hepatic artery.

Sonazoid造影超音波を用いた肝臓の組織進展度診断

Sonazoid造影超音波を用いた肝臓の組織進展度診断

A Case of Inflammatory Hepatocellular Adenoma Complicated by Steatohepatitis

A 54-year-old man with hypertension, dyslipidemia, diabetes mellitus and fatty liver was referred to our institution for accurate diagnosis of a 4-cm space-occupying lesion in subsegment 6 of the liver, identified on ultrasonography as an iso-to hypointense lesion with clear margins. Dynamic computed tomography disclosed light accumulation of contrast medium at the margins of the space-occupying lesion from the arterial phase through to the venous phase. Sonazoid-enhanced ultrasonography showed staining of the tumor margins in the vascular phase, disappearing in the post-vascular phase. Hepatic arteriography identified the space-occupying lesion as hypervascular. Since accurate diagnosis by imaging was difficult, tumor resection was performed to exclude hepatocellular carcinoma, after obtaining consent from the patient. Histological examination revealed steatohepatitis and sinusoidal dilatation, representing socalled peliosis hepatis, in the surroundings, while the tumor showed mild hepatocellular atypia. On immunohistochemistry, tumor cells were positive for liver fatty acid-binding protein, glutamine synthetase and serum amyloid A, and negative for β-catenin and glypican 3. Glutamine synthetase, in particular, showed strong diffuse staining. Inflammatory hepatocellular adenoma was thus considered the most likely diagnosis. The pathogenesis and outcome of inflammatory hepatocellular adenoma are not fully understood, and this case with concomitant steatohepatitis was considered worth reporting.

Abstract P2-03-07: Prediction of the pathological response to neoadjuvant chemotherapy in patients with breast cancer using sonazoid-enhanced ultrasonography

Abstract Background: Altered blood flow in malignant tumors is evidenced by contrast-enhanced ultrasonography (CEUS) because of its image perfusion capabilities. This study aimed to investigate the value of CEUS in the evaluation of the response of breast cancer lesions to neoadjuvant chemotherapy (NAC). We evaluated whether the prediction of a pathological complete response (pCR) using CEUS was more precise than that using other standard evaluation methods such as magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Methods: Ten patients (mean age, 50.2 years) who underwent NAC for invasive breast cancer between September 2012 and April 2013 were eligible for this cohort study. Clinical tumor response was evaluated using contrast-enhanced MRI, PET/CT, and CEUS following NAC. A pCR was defined as the absence of invasive cancer in the breast and lymph nodes according to the Japanese Breast Cancer Society criteria. A clinically complete response (cCR) was defined as the absence of residual disease on MRI and PET/CT. The HI VISION ASCENDUS (Hitachi Aloka Medical Corp.) was used for ultrasonography. Tumors were observed 50 s after Sonazoid injection at a dose of 0.01 ml/kg. A time-intensity curve of tumor signal intensity was drawn. The brightness of the tumor was digitized and the curve was created on the basis of brightness changes over time. The intensity of brightness of the breast cancer lesions was calculated as the increased rate of brightness (IRB) using the following formula: maximal intensity/intensity before contrast. Results: Four (40%) of the 10 patients were diagnosed with pCR by NAC. Among 4 (40%) patients diagnosed with cCR by MRI, 1 (25%) achieved pCR. All patients were diagnosed with pCR by PET/CT. The IRB values of the 10 patients who received CEUS before surgery were 1.0, 1.1, 1.2, 1.2, 1.3, 1.6, 1.8, 1.9, 2.5, and 4.2. The IRB values of the 4 patients diagnosed with pCR were 1.0, 1.1, 1.2, and 1.2. IRB values were significantly lower in patients who achieved pCR than in those who did not (pCR vs. no pCR, 1.1 ± 0.9 vs. 2.2 ± 1.0, P &amp;lt; 0.05). Furthermore, among the patients who achieved pCR, the IRB values of 2 patients with no residual ductal carcinoma in situ (DCIS) were 1.0 and 1.1, whereas those of 2 patients with residual DCIS were both 1.2. In the 4 patients who achieved cCR as diagnosed by MRI and PET/CT, 3 with pathological residual disease had detectable IRB by CEUS. table 1caseageStageSub typeMRIPET-CTpathological responseIncrease rate of brightness (IRB)167T2N1 IIBLuminal HER2PRCRCR1237T2N0 IIAHER2 positivePRCRCR1.1346T3N1 IIIAHER2 positiveCRCRCR1.2446T2N3c IIICLuminal HER2PRCRCR1.2564T2N0 IIAHER-2 positiveCRCRPR1.3658T2N1 IIBLuminal BCRCRPR1.6738T2N0 IIALuminal BPRCRPR1.8857T1cN0 ILuminal HER-2PRCRPR1.9939T2N1 IIBLuminalBSDCRSD2.51050T2N1 IIBTriple negativePRCRSD4.2 Conclusions: The prediction of pCR after NAC in patients with breast cancer is more precise with Sonazoid-enhanced ultrasonography than with standard methods such as MRI and PET/CT. Furthermore, CEUS may be useful for predicting residual DCIS on the basis of brightness intensity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-07.

Abstract P2-03-08: Usefulness of sonazoid-enhanced ultrasonography in the evaluation of the biological features of breast cancer

Abstract Background: Contrast-enhanced ultrasonography using Sonazoid (CEUS) has gained interest because of its ability to evaluate the vascularity of malignant tumors. This study aimed to investigate the relationship between biological marker expression and time-intensity curve values for signal intensity caused by the contrast effects of Sonazoid used during CEUS for breast cancer. Methods: We evaluated 32 patients with breast cancer (mean age, 45.4 years) using Sonazoid-enhanced ultrasonography between September 2012 and May 2013. Of these, 23 were diagnosed with invasive ductal carcinoma (IDC) and 9 were diagnosed with ductal carcinoma in situ (DCIS). Breast carcinoma was evaluated in terms of nuclear grade (NG), Ki-67 labeling index, and estrogen receptor (ER). Luminal types were categorized using the Ki-67 labeling index as follows: luminal A, ER-positive and Ki-67 &amp;lt; 30%; luminal B, ER-positive and Ki-67 &amp;gt; 30%. The HI VISION ASCENDUS (Hitachi Aloka Medical Corp.) was used for ultrasonography in this study. Tumors were observed 50 s after injection of 0.01 ml/kg of Sonazoid. Time-intensity curves for tumor signal intensity were drawn. The brightness in the tumor was digitized and the curves were created on the basis of changes in brightness over time. To indicate the intensity of brightness of breast cancer lesions on Sonazoid-enhanced ultrasonography, the increase rate of brightness (IRB) was calculated using the following formula: IRB = Maximum intensity x 1/Intensity before contrast. Results IRB was 1.6 ± 0.3 and 3.3 ± 2.2 in patients with DCIS and IDC, respectively, indicating a more significant increase in IDC patients (P &amp;lt; 0.05). Relation of tumour characteristics and brightness intensityCharactersticNo. of PatientsIncreased rate of brightness (IRB)p-valueNG 1, 2122.6 ± 1.00.713113.9 ± 2.9 Ki-67 &amp;lt; 3092.4 ± 0.7P &amp;lt; 0.05≥ 30144.7 ± 2.9 ER status positive213.3 ± 2.2 negative29.1 Sub type Luminal A102.4 ± 0.8P &amp;lt; 0.05Luminal B124.2 ± 2.7 On classification of patients with IDC according to NG, Ki-67, and ER, it was found that IRB values were 2.6 ± 1.0 in patients with NG 1 and 2 tumors and 3.9 ± 2.9 in those with NG 3 tumors, 2.4 ± 0.7 in patients with Ki-67 &amp;lt; 30% and 4.7 ± 2.9 in those with Ki-67 ≥ 30%, and 9.1 in ER-negative patients and 3.3 ± 2.2 in ER-positive patients (table 1). Furthermore, comparison according to luminal subtype revealed that IRB values were 2.4 ± 0.8 and 4.2 ± 2.7 in luminal A and luminal B cases, respectively, indicating a significant difference (P &amp;lt; 0.05) (table 1). Conclusions: The intensity of ultrasound brightness of breast cancer leasions, when digitized and analyzed, can be applied for the differential diagnosis of DCIS and IDC. Furthermore, brightness intensity may also exhibit correlations with NG, Ki-67 index, and luminal subtypes, suggesting that it can be applied in grading of malignancies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-08.

Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI

Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as well as uptakes of Sonazoid and Gd-EOB-DTPA by HCC. Seventy patients with 73 histologically proven HCCs (33 hypovascular well-differentiated HCCs and 40 progressed HCCs) and 9 dysplastic nodules (DNs) were enrolled. Enhancement patterns of the lesions on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were evaluated. Uptakes of Sonazoid and Gd-EOB-DTPA were assessed by Sonazoid enhancement index and EOB enhancement ratio in relation to immunohistochemistry of CD68 and organic anion transporting polypeptide 8 (OATP8), respectively. On the post-vascular phase of SEUS, none of the 9 DNs and 3 of 33 hypovascular well-differentiated HCCs (9 %) were hypoechoic, whereas 3 of 9 DNs (33 %) and 31 of 33 hypovascular well-differentiated HCCs (94 %) showed hypointensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Of 31 progressed HCCs, 95 and 93 % were hypoechoic and hypointense on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, respectively. Sonazoid enhancement indexes decreased in progressed HCCs, correlating with lower Kupffer cell numbers (P < 0.001). EOB enhancement ratios decreased in hypovascular well-differentiated and progressed HCCs, as OATP8 expression declined (P < 0.001). In stepwise hepatocarcinogenesis, uptake of Sonazoid starts decreasing later than that of Gd-EOB-DTPA. Although signal reductions on the post-vascular phase of SEUS or hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI suggest HCC, hypoechoic appearance on the post-vascular phase of SEUS might be HCC-specific, particularly progressed HCC.

Arrival time parametric imaging using Sonazoid-enhanced ultrasonography is useful for the detection of spoke-wheel patterns of focal nodular hyperplasia smaller than 3 cm

It is considered difficult to make a definitive diagnosis of focal nodular hyperplasia (FNH) of <3 cm when using conventional diagnostic imaging modalities. Typical FNH imaging findings are: i) central scar formation, ii) nutrient vessels extending radially from the center and iii) the presence of Kupffer cells. In a clinical setting, identification of a spoke-wheel pattern formed by nutrient vessels extending radially is a key feature in the diagnosis of FNH. In this study, we investigated the detection rate of spoke-wheel patterns of FNH <3 cm using arrival time parametric imaging (At-PI) technology with Sonazoid-enhanced ultrasonography (US). Five patients with FNH <3 cm who had undergone Sonazoid-enhanced US at the Toho University Omori Medical Center between February 2008 and March 2009 were included in the study. The mean tumor diameter was 20.2±7.2 mm. Lesions were enhanced with 0.5 ml Sonazoid US contrast agent and a video of the procedure was saved and used for At-PI analysis of contrast agent dynamics in FNH. Three ultrasonographic specialists examined the images and made a diagnosis of FNH based on the findings of spoke-wheel patterns. Similarly, micro-flow imaging (MFI) was performed to evaluate the contrast agent dynamics in FNH. Using MFI, FNH was diagnosed in 3 of the 5 cases by the three specialists, whereas At-PI enabled the identification of spoke-wheel patterns in all 5 cases. At-PI using Sonazoid-enhanced US is superior for detecting spoke-wheel patterns of FNH <3 cm.

Macroscopic and Histological Evaluation of Hepatocellular Carcinoma by Sonazoid-enhanced Ultrasonography

Macroscopic and Histological Evaluation of Hepatocellular Carcinoma by Sonazoid-enhanced Ultrasonography

Visualization of segmental arterialization with arrival time parametric imaging using Sonazoid-enhanced ultrasonography in portal vein thrombosis: A case report

A 55-year-old male was admitted in mid-April 2011 with a fever of >39°C and pain in the lower right abdomen. A medical examination revealed sepsis originating from colonic diverticulitis. Abdominal B-mode ultrasonography (US) performed on admission detected thrombi in the superior mesenteric vein and in the right branch of the hepatic portal vein. Arrival time parametric imaging (At-PI) using Sonazoid-enhanced US showed arterialization of the entire right lobe of the liver. The treatment for the sepsis and portal thrombi that had been started upon admission dissolved the thrombi by day 22, with the exception of one thrombus in the P8 branch of the portal vein. At-PI performed on the same day confirmed arterialization in segment 8, but portal vein dominance was restored elsewhere. When the blood inflow from the hepatic portal vein was reduced, the hepatic arterial blood flow was increased to compensate for the reduction in the total blood supply. The At-PI functions used in the Sonazoid-enhanced US were simple yet effective in visualizing the changes in the hepatic hemodynamics caused by the portal thrombus.