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Objective: The aim of the work described here was to develop a diagnostic model based on contrast-enhanced ultrasound (CEUS) features to improve performance in predicting the probability of malignancy for breast lesions with an enlarged enhancement extent on CEUS., Methods: In total, 299 consecutive patients who underwent CEUS examination and had confirmed pathological results were retrospectively enrolled. Among the 299 patients, an enlarged enhancement extent on CEUS was found in 142 patients. In this special cohort, we analyzed the association of malignant pathologic results with perfusion patterns emphatically by reclassifying the patterns., Results: A diagnostic model was developed and presented as a nomogram, assessed with discrimination and calibration. Receiver operating characteristic (ROC) curve analysis revealed that the areas under the curves of the conventional perfusion and modified perfusion patterns were 0.58 and 0.76 (p < 0.001), respectively. A diagnostic model was built and exhibited good discrimination with a C-index of 0.95 (95% confidence interval: 0.91-0.98), which was confirmed to be 0.93 via internal bootstrapping validation., Conclusion: The nomogram based on CEUS features provides radiologists with a quantitative tool to predict the probability of malignancy in this special cohort of breast lesions., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The aim was to retrospectively analyze the ultrasonographic and clinical characteristics of focal inflammatory masses and malignant masses of salivary gland by using B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) for differential analysis., Methods: The features of US and CEUS were retrospectively analyzed for 19 cases of focal salivary inflammatory masses and 45 cases of malignant salivary masses. All cases were confirmed by pathohistological examination., Results: On B-mode US, the incidence of expansive growth patterns of malignant salivary masses (44.4%, 20/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p = 0.029). The rate of lymphadenopathy surrounding salivary glands of malignant salivary masses (42.2%, 19/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p = 0.042). On CEUS, clear enhancement margins were more common in malignant salivary masses (44.4%, 20/45) compared to focal salivary inflammatory masses (15.8%, 3/19) (p = 0.029); Rapid washout was more common in malignant salivary masses (82.2%, 37/45) than focal salivary inflammatory masses (31.6%, 6/19) (p < 0.001). Rapid washout on CEUS and craniocaudal diameter were independent predictive factors in differentiating salivary inflammatory masses and malignant masses according to binary logistic regression analysis. US and CEUS achieved a sensitivity of 80.0%, a specificity of 78.9% and an accuracy of 80.0% for discrimination between salivary inflammatory masses and malignant masses., Conclusion: Therefore, a multimodal ultrasonographic pathway combining clinical manifestations, B-mode US and CEUS was needed to differentiate between salivary focal inflammatory masses and malignancies to avoid unnecessary biopsies.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients., Competing Interests: Christoph F Dietrich: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji, Boston Scientific, AbbVie, Falk Foundation, Novartis, Roche; Advisory Board Member, Hitachi, Mindray, Siemens; Research grant, GE, Mindray, SuperSonic Richard G Barr: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Philips, Siemens, Lantheus, Canon; Advisory Board – Lanteus and Bracco Diagnostics; Board Member – ICUS; Research Grants – Siemens Ultrasound, Philips Ultrasound, GE Ultrasound, GE Medical, Mindray, SuperSonic Imagine, B and K Ultrasound Annalisa Berzigotti: Research grant, Bracco Byung Ihn Choi: Speaker honoraria, Samsung Dirk André Clevert: Speaker honoraria, Bracco, GE, Samsung, Philips, Siemens, Falk Foundation Jean-Michel Correas: Speaker Honoraria, Canon MS, Hitachi MS, Philips US, SuperSonic Imagine, Novartis, Johnson & Johnson; Speaker honoraria, Bracco SA: Principal investigator of BR1-127 et SonoCap studies; Speaker honoraria, Guerbet SA: Principal investigator of NsSafe and Secure studies Odd Helge Gilja: Speaker honoraria, GE Healthcare, Takeda AS; Advisory Consulting, GE, Takeda and Samsung Vito Cantisani: Speaker honoraria, Samsung, Bracco, Canon J. Brian Fowlkes: Research grants, Philips Healthcare, GE Healthcare; Stock Ownership, Histosonics Adrian Lim: Advisory Board, Canon Medical Systems, Carestream; Research grant – Philips Medical Systems; Speaker honoraria – Canon, Bracco Maria Franca Meloni: Speaker honoraria, Bracco Christian Jenssen: Speaker honoraia, Hitachi, Bracco, Falk Foundation; Expert witness, Hitachi Mirko D’Onofrio: Speaker honoraria, Bracco, Siemens; Advisory Board, Bracco, Siemens, Hitachi; Research grant, Hitach; Congress Support, Bracco, Siemens Fabio Piscaglia: Speaker honoraria, Bracco, Bayer, EISAI, Guerbet; Advisory board honoraria: Bayer, EISAI; Research Contract: ESAOTE Masatoshi Kudo: Speaker honoraria, Bayer, Eisai, MSD, Ajinomoto; Research Grants, Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai, Bayer, Abbvie, Medico’s Hirata, Astellas Pharma, Bristol-Myers Squibb; Advisory Consulting, Kowa, MSD, BMS, Bayer, Chugai, Taiho, Eisai, Ono pharmaceutical Yi Dong: Speaker honoraria, Bracco, Siemens Yuko Kono: Equipment support Canon, GE; Contast agent support Lantheus, Bracco Andrej Lyshchik: Speaker honoraria, GE Healthcare, Siemens, Canon; Advisory Board, Bracco Diagnostics; Consulting, GE Healthcare; Speaker panel, GE Healthcare, SonoScape; Royalties, Elsevier Zheng Rongqin: Speaker honoraria, Bracco, Esaote; Research grant, Philips; Congress support, Bracco Paul Sidhu: Speaker honoraria, Bracco, Siemens, Hitachi, GE healthcare, Philips, Samsung, Advisory Board ITREAS Ltd The following have declared no conflict of interest: Peter Burns, Cristina Chammas, Nitin G Chaubal, Pintong Huang, Andre Ignee, Nathalie Lassau, Jae-Young Lee, Yasunori Minami, Carlos Nicolau, Christian Nolsoe, Xin-Wu Cui, Adrian Saftoiu, Guido Torzilli, Ping Liang, Fuminori Moriyasu, Xiaoyan Xie, (Thieme. All rights reserved.)

Objectives: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. However, differentiation of thrombosis and tumor-in-vein (TIV) may be challenging. Contrast-enhanced ultrasound (CEUS) is an excellent method for detection of vascularization and could help in the distinction. We performed a systematic review and meta-analysis for evaluating the diagnostic value of CEUS in differentiating between PVT and TIV in hepatocellular carcinoma (HCC) patients., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to the 5th of May 2019. The study quality was assessed by QUADAS-2 tool. Pooled sensitivity and specificity were calculated by the bivariate random effect model and hierarchical summary receiver-operating characteristic (SROC) curve was plotted., Results: Seven studies including 425 participants were analyzed after screening 986 articles searched from databases. The pooled sensitivity and specificity of CEUS in diagnosing TIV were 0.94 (95%CI, 0.89-0.97) and 0.99 (95%CI, 0.80-1.00), respectively. The area under the curve (AUC) of SROC curve was 0.97 (95%CI, 0.95-0.98). The pooled sensitivity and AUC were consistent across all the subgroups of different subject numbers, country, study design, CEUS contrast agents, and diagnostic criteria., Conclusions: CEUS is highly efficient in differentiating TIV from PVT and is an alternative or a substitute for CT and/or MRI., Trial Registration: PROSPERO registration number: CRD42019138847 KEY POINTS: • Characterization of portal vein thrombosis (PVT) vs tumor-in-vein (TIV) is critical for HCC staging. • CEUS has an excellent safety profile, provides a real-time analysis without any loss in accuracy compared with CT and MRI. • This meta-analysis demonstrates that contrast-enhanced ultrasound (CEUS) is a suitable method for the detection of PVT and distinction with TIV.

The aim of this study was to analyze the clinical manifestations of adverse reactions after the use of SonoVue contrast agent from a large retrospective database, and to evaluate the nursing care strategies and the efficacy of standardized procedure for adverse reactions of SonoVue (SPARS).From January 1, 2012 to December 30, 2018, 34,478 cases of contrast-enhanced ultrasonography were performed in our center. The clinical manifestations of adverse reactions after the use of SonoVue contrast agent were identified and analyzed. The nursing care strategies were evaluated and the outcomes of patients with moderate and severe adverse reactions before and after the application of SPARS were compared.Of the 34,478 cases, 40 cases (0.12%) of adverse reactions after the use of SonoVue were identified. Adverse reactions included anaphylatic shock, skin allergies, nausea or vomiting, dizziness or headache, numbness, chest distress, back pain, and local reactions of the injection site. Most of the adverse reactions were mild and self-limited. Only 3 cases of anaphylatic shock and 2 cases of severe rash underwent further treatments. The 3 patients who were managed by SPARS recovered quicker and spent less comparing with the other 2 patients who were not.SonoVue was a safe contrast agent, with few and mostly mild adverse reactions. SPARS may be an efficient way in tackling moderate to severe adverse reactions, although of which the incidence was rare.

Trans-rectal ultrasound-guided 12-core systematic biopsy (SBx) is the standard diagnostic pathway for prostate cancer (PCa) because of a lack of sufficiently accurate imaging. Quantification of 3-D dynamic contrast-enhanced ultrasound (US) might open the way for a targeted procedure in which biopsies are directed at lesions suspicious on imaging. This work describes the expansion of contrast US dispersion imaging algorithms to 3-D and compares its performance against malignant and benign disease. Furthermore, we examined the feasibility of a multi-parametric approach to predict SBx-core outcomes using machine learning. An area under the receiver operating characteristic (ROC) curve of 0.76 and 0.81 was obtained for all PCa and significant PCa, respectively, an improvement over previous US methods. We found that prostatitis, in particular, was a source of false-positive readings., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify the clinical role of contrast enhanced ultrasound (CEUS) in predicting BI-RADS 4 breast disease., Methods: A total of 92 sites of BI-RADS 4 breast diseases were reassessed by routine ultrasound and CEUS. The main indicators of routine ultrasound, CEUS and the combination of the two modalities were picked up by binary logistic regression analysis, scoring 0 for benign and 1 for malignant characteristics with pathology as referential standard to generate corresponding score systems of them. Finally, the receiver operating characteristic curves (ROC) were applied to compare the diagnostic efficacy of the three score systems., Results: As pathological results showing, there were 43 malignant and 49 benign sites in total. Binary logistic regression analysis indicated that the margin, micro-calcification, and hyperechoic halo were main indicators for routine ultrasound score system. The scope expansion and pathological vessels in CEUS were main indicators for CEUS score system. The microcalcification, hyperechoic halo, the scope expansion and pathological vessels in CEUS were main indicators for the combination score system of the two modalities. The sensitivity, specificity and the area under ROC curve (AUC) of routine US, CEUS and the combination of the two modalities score systems were 74.4%, 91.8%, 0.885 and 88.4%, 87.8%, 0.901 and 86.0%, 95.9%, 0.937, respectively., Conclusion: In summary, CEUS is helpful for us to identify malignant disease and plays a supplementary role in predicting BI-RADS 4 breast disease in some extent. The scope expansion and pathological vessels in CEUS may be the most useful indicators.

High intensity focused ultrasound (HIFU) has been regarded as a promising technology for treating cancer and other severe diseases noninvasively. In the present study, dual modality magnetic ultrasound contrast agent microbubbles (MBs) were synthesized by loading the super paramagnetic iron oxide nanoparticles (SPIOs) into the albumin-shelled MBs (referred as SPIO-albumin MBs). Then, both experimental measurements and numerical simulations were performed to evaluate the ability of SPIO-albumin MBs of enhancing HIFU-induced thermal effect. The results indicated that, comparing with regular albumin-shelled MBs, the SPIO-albumin MBs would lead to quicker temperature elevation rate and higher peak temperature. This phenomenon could be explained by the changes in MBs' physical and thermal properties induced by the integration of SPIOs into MB shell materials. In addition, more experimental results demonstrated that the enhancement effect on HIFU-induced temperature elevation could be further strengthened with more SPIOs combined with albumin-shell MBs. These observations suggested that more violent cavitation behaviors might be activated by ultrasound exposures with the presence of SPIOs, which in turn amplified ultrasound-stimulated thermal effect. Based on the present studies, it is reasonable to expect that, with the help of properly designed dual-modality magnetic MBs, the efficiency of HIFU-induced thermal effect could be further improved to achieve better therapeutic outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To investigate quantitative 3-D dynamic contrast-enhanced ultrasound (DCE-US) and, in particular 3-D contrast-ultrasound dispersion imaging (CUDI), for prostate cancer detection and localization, 43 patients referred for 10-12-core systematic biopsy underwent 3-D DCE-US. For each 3-D DCE-US recording, parametric maps of CUDI-based and perfusion-based parameters were computed. The parametric maps were divided in regions, each corresponding to a biopsy core. The obtained parameters were validated per biopsy location and after combining two or more adjacent regions. For CUDI by correlation (r) and for the wash-in time (WIT), a significant difference in parameter values between benign and malignant biopsy cores was found (p < 0.001). In a per-prostate analysis, sensitivity and specificity were 94% and 50% for r, and 53% and 81% for WIT. Based on these results, it can be concluded that quantitative 3-D DCE-US could aid in localizing prostate cancer. Therefore, we recommend follow-up studies to investigate its value for targeting biopsies., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Multi-parameter fitting algorithms, which are currently used for the characterization of coated-bubbles, inevitably introduce uncertainty into the results. Therefore, a better technique that can accurately determine the microbubbles' mechanical properties is urgently needed. A comprehensive technology combining atomic force microscopy, optical, and acoustic measurements with simulations of coated-bubble dynamics was developed. Using this technique, the mechanical parameters (size distribution, shell thickness, elasticity, and viscosity) of hybrid (ultrasound/magnetic-resonance-imaging) contrast microbubbles and their structure-property relationship were determined. The measurements indicate that when more superparamagnetic iron oxide nanoparticles are embedded in the microbubbles' shells, their mean diameter and effective viscosity increase, and their elastic modulus decreases. This reduces the microbubbles' resonance frequency and thus enhances acoustic scattering and attenuation effects., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To examine the value of CEUS as a non-invasive tool in detecting lateral neck metastasis (LNM) and the enhancement patterns of malignant lymph nodes (LN) for thyroid cancer patients., Methods: Eighty-two consecutive patients, who underwent both preoperative non-enhanced US and CEUS examinations, were retrospectively reviewed. All patients underwent lateral neck dissection (LND). Enhancement patterns of 102 collected LNs matching to CEUS findings were analyzed., Results: CEUS detected LNM in 53 of 65 patients, showing a higher sensitivity and accuracy than that of conventional US (p = 0.109 and p = 0.154, respectively). Thirteen patients' surgical procedures were altered by CEUS findings, including nine true positive and four false positive cases. Five patients' surgical procedures were altered by conventional US findings, including two true positive and three false positive cases. Heterogeneous enhancement, perfusion defects, microcalcification, and centripetal/hybrid enhancement were all specific criteria for malignant LNs in univariate analysis. In multivariate analysis, only heterogeneous enhancement and centripetal/hybrid enhancement were significantly related to LN metastasis (p = 0.000 and p = 0.037, respectively)., Conclusions: CEUS may be a potential tool to facilitate conventional US in detecting LNM. Heterogeneous enhancement and centripetal/hybrid enhancement are useful criteria to distinguish between malignant and benign LNs., Key Points: • CEUS findings facilitated conventional US in detecting LNM. • Heterogeneous, centripetal/hybrid enhancement, microcalcification and perfusion defects were specific criteria of malignant LNs. • Heterogeneous and centripetal/hybrid enhancement were significantly related to LN metastasis in multivariate analysis.

The aim of this study was to evaluate the relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerotic plaque in rabbit model. The abdominal aortas of thirty-six male New Zealand rabbits were damaged by balloon expansion and the animals were then fed a high fat diet for 12 weeks. Twenty-seven plaques on the near aortic wall were detected using conventional ultrasound examination. The maximum thickness of each plaque was recorded. CEUS was performed on these 27 plaques and the time-intensity curves (TICs) were analyzed offline. Using the quantitative ACQ software, features such as the arrival time (AT), time to peak (TTP), baseline intensity (BI), peak intensity (PI) and enhanced intensity (EI) (EI = PI-BI) were assessed. Inter- and intra-observer agreement of EI were assessed using the Bland-Altman test. After CEUS examination, the rabbits were sacrificed for pathological examination and CD34 monoclonal antibody immunohistochemical detection. Microvessel density (MVD) was counted under the microscope. The relationship between indexes of CEUS and the level of MVD was analyzed. There was a good positive linear correlation between EI and MVD (γ = 0. 854, P<0. 001), the intraclass correlations for inter- and intra-observer agreement for EI were 0.73 and 0.82 respectively, suggesting that EI may be act as a useful index for plaque risk stratification in animal models.

The aim of this study was to assess the relationship between the enhancement patterns and clinicopathological features of gastric cancer using intravenous contrast-enhanced ultrasonography (CEUS). In this Ethics Committee-approved prospective study, five hundred fifty two patients with gastric cancer who gave informed consent were examined preoperatively with CEUS. The enhancement pattern of each tumor was analyzed visually. Gross and histopathological findings on the postoperative specimens were compared with the preoperative CEUS findings. The most common CEUS pattern in differentiated gastric cancer was homogeneous enhancement, whereas heterogeneous enhancement was the most common pattern in undifferentiated gastric cancer. The proportion of heterogeneous enhancement was significantly different between the two histological subtypes (Chi- square = 146.735, P<0.001). The sensitivity and specificity of early heterogeneous enhancement on CEUS in diagnosing undifferentiated gastric cancer were 78.84% and 72.59% respectively. Gastric cancers with heterogeneous enhancement were more often Borrmann III and IV macroscopic types than those with homogeneous enhancement (66.56% vs. 30.80%, P<0.001), more commonly T3 and T4 depth of invasion than those with homogeneous enhancement (71.52% vs. 59.60%, P<0.05), more often showed lymphatic invasion than those with homogeneous enhancement (84.44% vs. 76.40%, P<0.05), and were less likely to receive curative gastrectomy than those with homogeneous enhancement (74.83% vs. 86.40%, P<0.005). The intra- and inter-observer reproducibility were both almost perfect for assessing enhancement patterns, with Kappa values of 0.916 (P<0.001) for intra-observer and 0.842 (P<0.001) for inter-observer reproducibility. CEUS provided detailed information about tumor vascularity and contrast enhancement patterns in gastric cancer. CEUS is promising as a new and useful method to predict the histological type of gastric cancer.

Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) is a standard for stratifying high-risk hepatocellular carcinoma (HCC) patients. In CEUS LI-RADS version 2017, the CEUS features are evaluated using pure-blood pool contrast agent, which might be inapplicable to perfluorobutane contrast agent in terms of Kupffer phase defect. This study aims to summarize and compare diagnostic performance of classical with modified CEUS LI-RADS using perfluorobutane by integrating published data and our original study data from three medical centers. • PubMed, Embase, Cochrane library and Web of Science were searched up to 31 August, 2023, observational (retrospective or prospective) or clinical trials of perfluorobutane contrast agent in diagnosing HCC in high-risk patients were included. • Quality Assessment of Diagnostic Accuracy Studies-2 tool was used. • Comparison between classical and modified CEUS LI-RADS with perfluorobutane were performed by ranking of diagnostic odds ratio and superiority index using an ANOVA arm-based model. • PROSPERO registration number: CRD42023461549. Nine studies plus our original data were included in this meta-analysis, relating to 1662 patients with 1779 lesions. 1. The summarized sensitivity of modified CEUS LI-RADS was higher than classical CEUS LI-RADS (0.77[0.72-0.81] vs. 0.7[0.63-0.76]). 2. The general diagnostic performance of modified CEUS LI-RADS was superior than classical CEUS LI-RADS with a higher diagnostic odds ratio (16.98[11.65,23.43] vs. 12.51[8.11,18.44]) and higher superiority index (1.59[1.00,3.00] vs. 0.80[0.33,1.00]). Modified CEUS LI-RADS using perfluorobutane contrast agent embraces better diagnostic performance with higher sensitivity without compromising specificity in high-risk HCC patients. [ABSTRACT FROM AUTHOR]