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Plaque elasticity and intraplaque neovascularisation are strongly suggestive of vulnerable plaque. This study aimed to investigate the relationship between intraplaque neovascularisation and plaque elasticity, and to compare the ultrasound findings with histopathological changes. Patients enrolled in this study presented with symptomatic carotid stenosis (> 70%) and later underwent both pre-operative ultrasonography and endarterectomy. Contrast enhanced ultrasound (CEUS) and shear wave elastography (SWE) were used to measure the neovascularisation and elasticity of the plaque, respectively. After removal, plaques were histologically assessed to determine the microvessel density (MVD), matrix metalloproteinase (MMP)-9 expression, and type I/type III collagen ratio using immunohistochemistry staining and morphometry. A correlation analysis was used to establish the relationship among the aforementioned quantitative parameters. Inter- and intra-observer consistency evaluations were performed using the intraclass correlation coefficient and Bland–Altman plots. Ninety-four symptomatic patients with 98 plaques were included. The area under the curve (AUC) of the carotid plaque detected using CEUS correlated with its shear wave velocity (SWV) (r = –.714; p <.001), MVD (r =.842; p <.001), collagen type I/III ratio (r = –.833; p <.001), and MMP-9 (r =.738; p <.001). SWE was positively correlated with the type I/III collagen ratio (r =.805; p <.001). The overall interexaminer consistency of the SWE was acceptable (r =.638; p <.001). The interobserver correlation coefficient of the AUC, time to peak (TP), mean transit time (MTT), and SWV were.719,.756,.733, and.686, respectively. The intra-observer variability values of the AUC, TP, MTT, and SWV were.826,.845,.633, and.748, respectively. SWE and CEUS can comprehensively evaluate the vulnerability of the carotid plaque by assessing the elasticity of the plaque and neovascularisation within it. The negative correlation between the intraplaque neovascularisation and elasticity, further validated by histological findings, suggests that the more abundant the neovascularisation, the less elasticity. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) represents a viable approach to overcoming the limited ability of photodynamic therapy to penetrate biological barriers. However, pancreatic tumors contain a hypoxic microenvironment that limits the efficacy of oxygen-dependent type II SDT, complicating efforts to develop reliable, stable, and hypoxia-tolerant sonosensitizer. Herein, a tablet-like TiO 2 /C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed and found to be hypoxia-tolerant and stable in response to repeated ultrasound irradiation, enabling the TiO 2 /C-mediated generation of large quantities of reactive oxygen species (ROS) and thereby achieving efficacious type I SDT. Importantly, this nanocomposite continued to generate ROS in response to repeated ultrasound irradiation, and was able to induce tumor cell apoptosis via SDT-induced DNA damage in vitro and in vivo. This TiO 2 /C nanocomposite also exhibited good biocompatibility and did not induce any apparent toxicity in vitro and in vivo. Together, these data highlight TiO 2 /C as a valuable nanocomposite capable of facilitating repeated type I SDT, making it a promising tool for the treatment of hypoxic solid pancreatic tumors. In this research, a tablet-like TiO 2 /C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed, which exhibited great stability upon repeated ultrasound irradiation, hypoxic-tolerant ability and good biocompatibility. After ultrasound irradiation, TiO 2 /C could efficiently generate reactive oxygen species in an oxygen-independent manner, which overcame the limitation of pure TiO 2 nanoparticles. Therefore, it was applied to repeated type I sonodynamic therapy of hypoxic pancreatic tumor. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs), with a primary occurrence in the duodenum and proximal jejunum, are rare and treatment is poorly understood. This study aimed to evaluate the main factors influencing the prognosis of GIST resection in this complex anatomical structure. This retrospective study included 47 patients who underwent surgery for primary GIST of the duodenum (20) and proximal jejunum (27) between 2012 and 2017. Perioperative clinical data as well as relapse and survival information were collected. All patients underwent negative margin resection (R0) of duodenal and proximal jejunum GISTs. Complications occurred more frequently in treatment of duodenal GISTs than proximal jejunum GISTs (p = 0.003). GISTs in D3 (the 3rd portion of duodenum) were related to larger tumor size (p = 0.001), higher probability of severe complication rate (p = 0.042), longer hospital stays (p = 0.023) and fasting time (p = 0.020). More complications were found for patients with digestive reconstruction than limited resection (p = 0.010). Additionally, patients with a tumor mass larger than 5 cm or a mitotic index greater than 5 mitoses/50 HPFs showed poorer therapeutic outcomes. The 1- and 3-year overall survival was 97.9% and 86.1%, respectively and were not influenced by operation type (p = 0.061) or GIST position (p = 0.447). With negative operational margins, limited resection is a safe and feasible procedure for duodenal and proximal jejunum GIST patients and unnecessary digestive reconstruction should be avoided. Considering the severe complication rate, resection for GISTs in D3 should be performed with care. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate the practicability of transvaginal 4-dimensional (4D) hysterosalpingo-contrast sonography (HyCoSy) using SonoVue for screening of fallopian tube patency in infertile females.Design: Prospective observational study (Canadian Task Force classification II-2).Setting: The Second Affiliated Hospital of Zhejiang University.Patients: 204 infertile females who underwent 4D-HyCoSy between July 2015 and June 2016.Intervention: 4D-HyCoSy was performed to acquire dynamic images. If any of the fallopian tubes was not developing during the process, the procedure was repeated promptly, to exclude false-positive outcomes. Subsequently, tube status was confirmed by traditional 2-dimensional (2D)-HyCoSy. Finally, the results of the 4D-HyCoSy and the final 2D-HyCoSy were compared.Measurements and Main Results: A total of 204 patients (408 tubes) were evaluated ith 4D-HyCoSy followed by 2D-HyCoSy. Of these 408 tubes, 385 demonstrated the same status on 4D-HyCoSy and 2D-HyCoSy, for an agreement rate of 94.4%.Conclusion: A 4D technique combined with HyCoSy is a practicable screening method for assessing fallopian tube patency. It overcomes the disadvantages of 2D-HyCoSy and has a relatively high degree of agreement with the more difficult 2D-HyCoSy technique. [ABSTRACT FROM AUTHOR]

Purpose: To test the feasibility, safety, and efficacy of microwave (MW) ablation for primary hyperparathyroidism (pHPT) in patients who are unsuited or unwilling to undergo surgery.Materials and Methods: Fifteen patients with benign parathyroid nodules were treated with MW ablation. Ultrasound, laboratory data, and clinical symptoms were evaluated before treatment; 1 week and 1, 3, 6, and 12 months after treatment; and every 6-12 months thereafter.Results: All patients were followed up for more than 1 year, with an average duration of 32.8 months ± 17.9. Eleven patients underwent successful ablation in a single session, and two patients with bilateral disease and two patients with residual disease were treated with two sessions each. The rate of complete nodule disappearance was 17.6%. Nodule volume and serum parathyroid hormone (PTH) and calcium levels were significantly lower at the last follow-up than before treatment (volume, 0.39 cm(3) ± 0.69 vs 2.62 cm(3) ± 3.32; PTH, 54.5 pg/mL ± 24.1 vs 592.5 pg/mL ± 579.1; and calcium, 2.32 mmol/L ± 0.12 vs 2.93 mmol/L ± 0.47; P < .01). Treatment was well tolerated. Minor complications included transient voice change in one patient.Conclusions: MW ablation is a safe and effective technique for the treatment of pHPT. It is a good alternative for patients who do not meet surgery criteria or decline surgery. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the efficacy of concurrent delivery of an anti-angiogenic drug and ultrasonic cavitation therapy in a mouse model of human colon cancer. A biotinylated form of the anti-angiogenic drug Endostar was conjugated to a streptavidin-coated microbubble (MB). Mice bearing subcutaneous tumors (HT29) were divided into 4 groups. Group 1 served as an untreated control. Group 2 served as a cavitation control and received naked microbubbles and sham ultrasonic cavitation (MB+sham cavitation). Group 3 received naked microbubbles and ultrasonic cavitation (MB+cavitation). Group 4 received Endostar loaded microbubbles and ultrasonic cavitation (Endostar-MB+cavitation). Ultrasonic cavitation was performed using a high-power custom built sonicator. Contrast-enhanced ultrasound imaging (CEUS) was used to measure tumor blood flow before and after ultrasonic cavitation. In vivo fluorescence imaging was performed to monitor changes in tumor volume. Immunohistochemistry was performed to assess CD31, VEGFR-2 and alpha-v beta-3 integrin expression within the tumor. Apoptosis of the tumor cells was determined by TUNEL assay, and ultrastructural changes within the tumor were examined by electron microcopy. Ultrasonic cavitation with Endostar-MB demonstrated a significantly greater inhibition of tumor blood flow on day 7 and tumor growth on day 16 compared with naked MB and control groups. The Endostar-MB treated mice showed significantly decreased expression VEGFR-2 and alpha-v beta-3 integrin, and increased apoptosis of tumor cells and degradation of the tumor ultrastructure. Our findings indicated that the anti-vascular and anti-tumor effects of ultrasonic cavitation could be potentiated by simultaneously delivering an anti-angiogenic drug in colon cancer. [Copyright &y& Elsevier]

Abstract: The goal of this study was to determine whether ultrasound mediated microbubbles destruction (UMMD) could inhibit colon cancer growth in a mouse model. Six-week-old balb/c female nude mice were subcutaneously inoculated with HT29-GFP cells (HT29 cells labeled with green fluorescent dye) in axilla to establish a xenograft mouse model of colon carcinoma, which were randomly divided into five groups (n =10 each): group A (blank group): no treatment; group B (saline only); group C (saline+ultrasound exposure); group D (intravenous microbubbles only); and group E (intravenous microbubbles+ultrasound exposure). Treatment of each group was performed on days 20, 21, and 22 after inoculation. Tumor growth and metastatic spread were monitored by the whole-body fluorescent imaging, tumor volume growth and body weight growth curve were obtained as well. The mice were euthanized 30days after treatment. Specimens of the tumor tissues were evaluated pathologically using light microscopy and transmission electron microscopy. Necrosis percentages, microvascular density and tumor cells damage of each tumor were assessed histologically. Our data indicate that: (1) tumor growth in group E (intravenous microbubbles+ultrasound exposure) was significantly decreased after four weeks post inoculation, compared with other control treatments (P <0.05); (2) the tumor weight at sacrifice in group E was significantly lower than that in other groups; (3) The intravenous microbubbles combined with ultrasound exposure treated mice showed significantly decreased expression levels of CD31. (4)The pathological changes of absence of nucleus membrane, chromatin condensation, mitochondrial vacuolation and hemorrhagic damage of microvessel were observed in the tumors of group E only, whereas these changes occurred rarely in other groups; and (5) no metastatic lesion was found in any group throughout this study using whole-body fluorescent imaging, and the skin of the mouse in group E was intact after UMMD treatment. Our results suggest that UMMD can be used as a promising novel therapeutic strategy to treat colon cancer. [Copyright &y& Elsevier]

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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Although conventional ultrasound (CUS) allows for clear detection of parotid gland lesions (PGLs), it fails to accurately provide benign-malignant differentiation due to overlapping morphological features. Radiomics is capable of processing large-quantity volume of data hidden in CUS image undiscovered by naked eyes. The aim was to explore the potential of CUS-based radiomics score (Rad-score) in distinguishing benign (BPGLs) and malignant PGLs (MPGLs). A consecutive of 281 PGLs (197 in training set and 84 in test set) with definite pathological confirmation was retrospectively enrolled. 1465 radiomics features were extracted from CUS images and Rad-score was constructed by using Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Different nomogram models, including clinic-radiomics (Clin + Rad-score), CUS-clinic (CUS + Clin) and combined CUS-clinic-radiomics (CUS + Clin + Rad-score), were built using logistic regression. The diagnostic performance of different models were calculated and compared by area under receiver operating curve (AUC) and corresponding sensitivity and specificity. Finally, 26 radiomics features were independent signatures for predicting MPGLs, with MPGLs having higher Rad-scores in both cohorts (both P < 0.05). In the test population, CUS + Clin + Rad-score obtained an excellent diagnostic result, with significantly higher AUC value (AUC = 0.91) when compared to that of CUS + Clin (AUC = 0.84) and Clin + Rad-score (AUC = 0.74), respectively (both P < 0.05). In addition, the sensitivity of this combined model was higher than that of single Rad-score model (100.00% vs. 71.43%, P = 0.031) without compromising the specificity value (82.86% vs. 88.57%, P = 0.334). The calibration curve and decision curve analysis also indicated the clinical effectiveness of the proposed combined nomogram. The combined CUS-clinic-radiomics model may help improve the discrimination of BPGLs from MPGLs. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a severe disease that threatens human health. The hypoxic tumor microenvironment in pancreatic cancer leads to resistance to conventional therapies and helps to maintain tumor malignancy. First-line drugs present the disadvantage of systemic side effects, and a synergistic method with sonodynamic therapy (SDT) has been established as an emerging approach. In this study, we produced hypoxia-alleviating nanoplatforms (denoted as PZGI NPs) with zeolitic imidazolate frameworks-90 (ZIF-90) nanoparticles nucleating on platinum (Pt) nanoparticles and co-loaded with gemcitabine and IR780. This platform can catalyze peroxide to oxygen with loaded Pt nanoparticles to alleviate tumor hypoxia. Moreover, the loaded drugs could be quickly released in the lysosome microenvironment, which has a low pH value and high ATP level microenvironment in the mitochondria. This strategy could enhance the sensitivity of cancer cells to chemotherapy. Further, under ultrasound exposure, it could transfer the produced oxygen into a highly cytotoxic singlet oxygen for the augmented sonodynamic effect. Therefore, this multifunctional hypoxia-alleviating nanoplatform offers a promising strategy for chemo-sonodynamic therapy against pancreatic cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice. [ABSTRACT FROM AUTHOR]

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/cm2 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immunotherapy is considered as a promising therapeutic approach for cancer treatment. This therapy focuses on the specificity and memory of the immune system against malignant cells to achieve a sustained cure with minimal toxicity. However, the effectiveness of immunotherapy is often limited by the insufficient delivery and low accumulation of therapeutic molecules in tumors. Ultrasound exposures with the presence of microbubbles can be used as an effective method to greatly increase cell membrane permeability and enhance tissue accessibility to drugs or genes, thereby improving the access of therapeutic molecules into non-permeable tissues and enhancing the therapeutic outcomes. In this review, we discuss challenges in current tumor immunotherapy and feasible approaches that could potentially overcome these obstacles with the help of ultrasound; thereafter, we elaborate on the recent advantages of ultrasound-mediated delivery approach in tumor immunotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether ultrasound (US) mediated microbubbles (MBs) destruction (UMMD) could inhibit VX2 orthotopic hepatic tumor growth in rabbit models. Twenty-four VX2 orthotopic hepatic tumor rabbit models were randomly divided into four groups (n  =  6 each): saline group, SonoVue alone group, US alone group, US + SonoVue group. Tumor volume (TV), peak intensity (PI) of contrast enhanced ultrasound (CEUS) in US + SonoVue group were significantly lower than that in other groups after treatment ( P   <  0.05, for all). Immunohistochemical analysis of tumor tissue showed that microvascular density (MVD) in US + SonoVue group was significantly lower than that in other groups ( P   <  0.05, for all). Extensive interstitial hemorrhage, intravascular thrombosis, destroyed nucleus membrane, mitochondria vacuolation and chromatin condensation were observed in US + SonoVue group, whereas these changes were rarely appeared in other groups. Our study indicated that UMMD could inhibit the growth of VX2 hepatic tumors in rabbits by irreversible destroying tumor microvessel and tumor cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) diagnosis still relies on 12-core systematic biopsy (SBx). More recently, pre-biopsy multiparametric MRI has been introduced in the guidelines as a valuable imaging tool for the detection of significant PCa. However, poor reproducibility and specificity, along with its high cost and limited availability, evidence the need for cost-effective, widespread imaging alternatives. 3D contrast-enhanced ultrasound (CEUS) has shown promise for PCa localization by extraction of quantitative perfusion and dispersion features associated with cancer angiogenesis. Tissue stiffness is an additional PCa biomarker that can be quantified by ultrasound shear-wave elastography (SWE). In this study, the diagnostic potential of multiparametric ultrasound imaging, combining 3D CEUS and SWE features, was evaluated for PCa localization by comparison with the corresponding SBx outcome. After signing an informed consent, 54 biopsy-naïve patients underwent a 3D CEUS recording using a LOGIQ E9 scanner (GE HealthCare, USA) and a multi-plane (probe sweep) 2D SWE scan using an Aixplorer scanner (SuperSonic Imagine, France) at the Second Affiliated Hospital of Zhejiang University (China). All patients received SBx. Multiple 3D perfusion and dispersion feature maps were extracted from the 3D CEUS acquisitions and further complemented with 3D maps of tissue stiffness, reconstructed based on the multi-plane 2D SWE acquisitions. Subsequently, all the 3D maps were subdivided in 12 regions corresponding to the SBx locations. Gradient Boosting (GB) classification was then implemented together with sequential floating forward feature selection for prediction of the biopsy outcome. The classification accuracy was assessed by a k-fold cross-validation procedure. Of the 54 patients, 20 had SBx-proven significant PCa. Prediction of biopsy outcome using only CEUS features produced an area under the receiver-operating-characteristic curve (AUC) of 0.81, while using the SWE elasticity alone produced an AUC of 0.66. Their combination yielded an improved AUC of 0.85. The proposed 3D multiparametric ultrasound imaging approach yields accurate PCa classification results, showing promise for cost-effective PCa localization by multiparametric ultrasound imaging. A multicenter trial has recently started to validate and optimize the classification performance in a larger patient cohort. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNA's expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins. [ABSTRACT FROM AUTHOR]

Abstract: 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 (E p), arterial compliance, augmentation index and local pulse wave velocity (PWVβ) were measured with echo tracking. We also determined the systolic (D s) and diastolic (D d) lumen diameters of the common carotid artery and systolic (P s) and diastolic (P d) pressures. The differences in β, E p 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 D s and D d among the three groups were statistically significant (p < 0.05). Differences in P s and P d 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. [Copyright &y& Elsevier]