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Objectives: To assess the value of 3D multiparametric ultrasound imaging, combining hemodynamic and tissue stiffness quantifications by machine learning, for the prediction of prostate biopsy outcomes., Methods: After signing informed consent, 54 biopsy-naïve patients underwent a 3D dynamic contrast-enhanced ultrasound (DCE-US) recording, a multi-plane 2D shear-wave elastography (SWE) scan with manual sweeping from base to apex of the prostate, and received 12-core systematic biopsies (SBx). 3D maps of 18 hemodynamic parameters were extracted from the 3D DCE-US quantification and a 3D SWE elasticity map was reconstructed based on the multi-plane 2D SWE acquisitions. Subsequently, all the 3D maps were segmented and subdivided into 12 regions corresponding to the SBx locations. Per region, the set of 19 computed parameters was further extended by derivation of eight radiomic features per parameter. Based on this feature set, a multiparametric ultrasound approach was implemented using five different classifiers together with a sequential floating forward selection method and hyperparameter tuning. The classification accuracy with respect to the biopsy reference was assessed by a group-k-fold cross-validation procedure, and the performance was evaluated by the Area Under the Receiver Operating Characteristics Curve (AUC)., Results: Of the 54 patients, 20 were found with clinically significant prostate cancer (csPCa) based on SBx. The 18 hemodynamic parameters showed mean AUC values varying from 0.63 to 0.75, and SWE elasticity showed an AUC of 0.66. The multiparametric approach using radiomic features derived from hemodynamic parameters only produced an AUC of 0.81, while the combination of hemodynamic and tissue-stiffness quantifications yielded a significantly improved AUC of 0.85 for csPCa detection (p-value < 0.05) using the Gradient Boosting classifier., Conclusions: Our results suggest 3D multiparametric ultrasound imaging combining hemodynamic and tissue-stiffness features to represent a promising diagnostic tool for biopsy outcome prediction, aiding in csPCa localization., Competing Interests: Conflict of interest Prof. Massimo Mischi and Prof. Hessel Wijkstra are the advisors of the company Angiogenesis Analytics (the Netherlands)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

The purpose of this study was to investigate the role of contrast-enhanced ultrasound (CEUS) in determining the viable target area in patients with subpleural pulmonary lesions before ultrasound-guided transthoracic core biopsy. In this retrospective study, we analyzed 92 patients with subpleural pulmonary lesions (63 males and 29 females; mean age: 65.17 ± 11.72 y). All patients underwent B-mode ultrasound, color Doppler and CEUS. Color Doppler was performed to identify the major vessels. The time to enhancement of the contrast agents, homogeneity of enhancement and the presence of areas without enhancement were recorded after administration of the contrast agents. The viable target areas were defined as regions showing enhancement relative to those without enhancement and regions showing delayed enhancement in reference to peripheral lung tissues showing early enhancement. Afterward, real-time ultrasound-guided transthoracic core needle (18 gauge) biopsies were performed and the complication rate, success rate and diagnostic accuracy were calculated. With CEUS, the needle pathways of these lesions were readjusted the biopsy strategy in 40/92 patients (43.5%). It was determined that the satisfactory rate of the subsequent biopsy specimen was 100%. The histologic diagnostic accuracy of the biopsy was 97.83%. No serious complications occurred during the biopsy. In conclusion, the application of CEUS before biopsy was able to depict the viable target areas of the lesion to readjust the biopsy routes. With the help of CEUS, ultrasound-guided core biopsy could obtain adequate samples, improve the diagnostic accuracy and reduce the complication rates of biopsies., Competing Interests: Conflict of interest disclosure The authors have no conflict of interest to disclose., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to identify the potential and mechanisms of microbubble-mediated cavitation in promoting apoptosis and suppressing invasion in cancer cells. AsPC-1 cells were used and divided into four groups: control group, microbubble-only (MB) group, ultrasound-only (US) group and ultrasound plus microbubble (US + MB) group. Pulse ultrasound was used at a frequency of 360 kHz and a SPPA (spatial peak, pulse average) intensity of 1.4 W/cm 2 for 1 min (duty rate = 50%). Then cells in the four groups were cultured for 24 h. Cell Counting Kit‑8 (Biosharp, Hefei, Anhui, China) revealed decreased cell viability in the US + MB group. Western blot confirmed that there were increased cleaved caspase‑3 and Bcl-2-associated X protein levels and decreased B‑cell lymphoma‑2 (Bcl-2) levels, as well as increased intracellular calcium ions and downregulated cleaved caspase-8, in the US + MB group. With respect to proliferation, cells in the US + MB group had lower expression of Ki67 and the weakened colony formation ability. The transwell invasion assay revealed that invasion ability could be decreased in AsPC-1 cells in the US + MB group. Further, it was found that cells in the US + MB group had lower levels of hypoxia-inducible factor-1α (HIF-1α) and vimentin and higher levels of E-cadherin compared with the other three groups. Finally, the US + MB cells had less invadopodium formation. In conclusion, these results suggest that microbubble-mediated cavitation promotes apoptosis and suppresses invasion in AsPC-1 cells., Competing Interests: Conflict of interest disclosure The authors declare there are no competing financial interests in relation to this research., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. 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 in 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 U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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.)

Agreement between ultrasound strain elastography (SE) scores of transverse and longitudinal views of thyroid nodules was investigated, and the diagnostic performance of these scores in predicting thyroid malignancy was assessed. From December 2016 to February 2017, a total of 250 thyroid nodules in 232 patients (62 males and 188 females, mean age: 45 y [20-75 y]) were enrolled. Diagnostic agreement between SE scores obtained in different views was assessed. Sensitivity, specificity, area under the receiver operating characteristic curve (Az) of the SE score in different criteria (criterion 1, SE score ≥4 from any view is defined as suspicious; criterion 2, SE score ≥4 as in only transverse view; and criterion 3, SE score ≥4 only from longitudinal view) were evaluated. Diagnostic agreement between SE scores of different views was fair (κ = 0.227). The Az value for criterion 1 (0.770, 95% confidence interval [CI]: 0.713, 0.820) was the highest among the three criteria, significantly higher than that of criterion 2 (0.692, 95% CI: 0.631, 0.749) (p < 0.001), but not statistically significantly different from that of criterion 3 (0.768, 95% CI: 0.711, 0.819) (p = 0.909). However, the Az value for criterion 3 was higher than that for criterion 2 (p < 0.005). The results indicated that criterion 1 had high sensitivity (80.0%) and criterion 2 had high specificity (68.0%). Our study found that the agreement between SE scores of different views was fair. SE scores ≥4 in either view were most sensitive for predicting malignant thyroid nodules., (Copyright © 2019 The Authors. Published by Elsevier Inc. 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.)

The aim of this study was to compare the accuracy of multi-detector computed tomography (MDCT) with double contrast-enhanced ultrasound (DCEUS), in which intravenous microbubbles are used alongside oral contrast-enhanced ultrasound, in determining the gross classification of patients with gastric carcinoma (GC). Altogether, 239 patients with GC proved by histology after endoscopic biopsy were included in this study. DCEUS and MDCT were performed pre-operatively. The diagnostic accuracies of DCEUS and MDCT in determining the gross classification were calculated and compared. The overall accuracy of DCEUS in determining the gross appearance of GC was higher than that of MDCT (84.9% vs. 79.9%, p < 0.001). There was no significant difference in accuracy between DCEUS and MDCT for Borrmann I and IV classifications of advanced gastric cancer (χ(2), p = 0.323 for Borrmann type I, p = 0.141 for Borrmann type IV). The accuracy of DCEUS for early GC and Borrmann II and III classifications of GC was higher than that of MDCT (χ(2), p = 0.000 for all). DCEUS may be regarded as a valuable complementary tool to MDCT in determining the gross appearance of gastric adenocarcinoma pre-operatively., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to examine the applicability of echo tracking to evaluation of common carotid artery wall elasticity in smokers and the effects of hypertension, hyperlipidemia and hyperglycemia on common carotid artery wall elasticity in smokers. Subjects were divided into three groups based on smoking status and presence of complications: group A (healthy control group), group B1 (simple smoking group) and group B2 (smoking with complications group). Complications included one or several symptoms of hypertension, hyperlipidemia and hyperglycemia. Intima-media thickness (IMT) of the common carotid artery was measured with ultrasound, and wall stiffness index(β), pressure-strain elasticity modulus (Ep), arterial compliance, augmentation index and local pulse wave velocity (PWVβ) were measured with echo tracking. We also determined the systolic (Ds) and diastolic (Dd) lumen diameters of the common carotid artery and systolic (Ps) and diastolic (Pd) pressures. The differences in β, Ep and PWVβ among the three groups in this study were statistically significant (p < 0.05). Augmentation index was increased in group B2 compared with groups B1 and A, with the differences being statistically significant (p < 0.05). Differences in augmentation index between groups B1 and A, differences in arterial compliance among the three groups and differences in intima-media thickness among the three groups were not statistically significant (p > 0.05), but differences in Ds and Dd among the three groups were statistically significant (p < 0.05). Differences in Ps and Pd between groups A and B1 were not statistically significant (p > 0.05), whereas those between groups B1 and B2 were statistically significant (p < 0.05). Echo tracking can be used to quantitatively evaluate the effect of smoking on common carotid artery wall elasticity and the effects of hypertension, hyperlipidemia and hyperglycemia on common carotid artery wall elasticity in smokers., (Published by Elsevier Inc.)