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Objectives: To establish superb microvascular imaging (SMI) based thyroid imaging reporting and data system (SMI TI-RADS) for risk stratification of malignancy in thyroid nodules. Methods: In total, 471 patients, comprising 643 thyroid nodules, who received conventional ultrasound (US), SMI, and a final diagnosis were extensively analyzed. A qualitative assessment of US features of the nodules was performed followed by univariable and multivariable logistic regression analyses, leading to the construction of the SMI TI-RADS, which was further verified using internal and external validation cohorts. Results: Among the stand-alone US, predictive factors were the shape and margins of the nodules, echogenicity and echogenic foci, vascularity, extrathyroidal extension, ring-SMI patterns, penetrating vascularity, flow-signal enlarged, and vascularity area ratio. SMI TI-RADS depicted an enhanced area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.92, 0.96; p < 0.001 relative to other stratification systems), a 79% biopsy yield of malignancy (BYM, 189/240 nodules), and a 21% unnecessary biopsy rate (UBR, 51/240 nodules). In the verification cohorts, we demonstrated AUCs, malignancy biopsy yields, and unnecessary biopsy rates of 0.88 (95% CI: 0.83, 0.94), 79% (59/75 nodules), and 21% (16/75 nodules) for the internal cohort, respectively, and 0.91 (95% CI: 0.85, 0.96), 72% (31/43 nodules), and 28% (12/43 nodules) for the external cohort, respectively. Conclusion: SMI TI-RADS was found to be superior in diagnostic sensitivity, specificity, and efficiency than existing TI-RADSs, showing better stratification of the malignancy risk, and thus decreasing the rate of unnecessary needle biopsy. Critical relevance statement: To develop an imaging and data system based on conventional US and SMI features for stratifying the malignancy risk in thyroid nodules. Key Points: SMI features could improve thyroid nodule risk stratification. SMI TI-RADS showed superior diagnostic efficiency and accuracy for biopsy guidance. SMI TI-RADS can provide better guidance for clinical diagnosis and treatment of thyroid nodules. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque in the carotid artery is the main cause of ischemic stroke, with a high incidence rate among people over 65 years. A timely and precise diagnosis can help to prevent the ischemic event and decide patient management, such as follow up, medical, or surgical treatment. Presently, diagnostic imaging techniques available include color-Doppler ultrasound, as a first evaluation technique, computed tomography angiography, which, however, uses ionizing radiation, magnetic resonance angiography, still not in widespread use, and cerebral angiography, which is an invasively procedure reserved for therapeutically purposes. Contrast-enhanced ultrasound is carving out an important and emerging role which can significantly improve the diagnostic accuracy of an ultrasound. Modern ultrasound technologies, still not universally utilized, are opening new horizons in the arterial pathologies research field. In this paper, the technical development of various carotid artery stenosis diagnostic imaging modalities and their impact on clinical efficacy is thoroughly reviewed. [ABSTRACT FROM AUTHOR]

Although predicting temperature variation is important for designing treatment plans for thermal therapies, research in this area is yet to investigate the applicability of prevalent thermal conduction models, such as the Pennes equation, the thermal wave model of bio-heat transfer, and the dual phase lag (DPL) model. To address this shortcoming, we heated a tissue phantom and ex vivo bovine liver tissues with focused ultrasound (FU), measured the temperature response, and compared the results with those predicted by these models. The findings show that, for a homogeneous-tissue phantom, the initial temperature increase is accurately predicted by the Pennes equation at the onset of FU irradiation, although the prediction deviates from the measured temperature with increasing FU irradiation time. For heterogeneous liver tissues, the predicted response is closer to the measured temperature for the non-Fourier models, especially the DPL model. Furthermore, the DPL model accurately predicts the temperature response in biological tissues because it increases the phase lag, which characterizes microstructural thermal interactions. These findings should help to establish more precise clinical treatment plans for thermal therapies. [ABSTRACT FROM AUTHOR]

Ultrasound super-resolution imaging through localisation and tracking of microbubbles can achieve sub-wave-diffraction resolution in mapping both micro-vascular structure and flow dynamics in deep tissue in vivo. Currently, it is still challenging to achieve high accuracy in localisation and tracking particularly with limited imaging frame rates and in the presence of high bubble concentrations. This study introduces microbubble image features into a Kalman tracking framework, and makes the framework compatible with sparsity-based deconvolution to address these key challenges. The performance of the method is evaluated on both simulations using individual bubble signals segmented from in vivo data and experiments on a mouse brain and a human lymph node. The simulation results show that the deconvolution not only significantly improves the accuracy of isolating overlapping bubbles, but also preserves some image features of the bubbles. The combination of such features with Kalman motion model can achieve a significant improvement in tracking precision at a low frame rate over that using the distance measure, while the improvement is not significant at the highest frame rate. The in vivo results show that the proposed framework generates SR images that are significantly different from the current methods with visual improvement, and is more robust to high bubble concentrations and low frame rates. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. Methods: We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. Results: The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5–33%)/ moderate (> 33–66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: − 0.449, p = 0.008; − 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). Conclusion: The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare the application value of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) guidelines in the risk stratification of thyroid isthmic nodules. METHODS: A total of 315 patients with thyroid isthmic nodules (315 nodules) confirmed by surgical pathology or fine-needle aspiration biopsy (FNAB) were selected in this retrospective study. The nodules were evaluated and classified according to ACR TI-RADS and the ATA guidelines. Taking pathological results as the reference, receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic capabilities of the ACR TI-RADS and the ATA guidelines for the risk stratification of thyroid isthmic nodules. The unnecessary biopsy rates and false-negative rates were compared. RESULTS: Multivariate analysis of ultrasonographic features of suspicious malignancies showed that an aspect ratio > 1 was not an independent risk factor for malignant thyroid nodules located in the isthmus (odds ratio: 3.193, 95%confidence interval: 0.882–11.552) (P = 0.077). The area under the ROC curves for diagnosing malignant thyroid nodules located in the isthmus in by the ACR TI-RADS and the ATA guidelines were 0.853 and 0.835, respectively. Under the management recommendations of the ACR TI-RADS and ATA guidelines, the false-negative rates of malignant thyroid nodules were 66.2%(ATA intermediate suspicion), 62.3%(ACR TR 4), 81.8%(ATA high suspicion) and 86.5%(ACR TR 5). CONCLUSION: Both the ACR TI-RADS and the ATA guidelines have high diagnostic capabilities for the risk stratification of thyroid isthmic nodules. For ACR TR 4 and 5 and ATA intermediate- and high-suspicion thyroid isthmic nodules with a maximum diameter < 1 cm, the criteria for puncture should be lowered, and FNAB should be done to clarify their diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to describe the characteristics of superficial desmoid fibromatosis (DF) using two-dimensional and contrast-enhanced ultrasonography, intending to improve diagnostic accuracy. We retrospectively analyzed 19 cases of superficial DF confirmed by surgery or core-needle biopsy in our hospital from January 2018 to August 2020. All patients underwent two-dimensional and contrast-enhanced ultrasound (CEUS) examination. Nineteen patients included 15 women and 4 men, with an average age of 33.37±12.13 years old. The mean size of lesions was 4.78±1.99 cm. On ultrasound, all lesions presented as solitary heterogeneous hypoechoic masses; 13 presented with ill-defined margins. Ten lesions (52.63%) presented with fusiform shapes, and 11 lesions (57.89%) presented with the "fascial tail" sign. CEUS suggested the tumors were hyperenhanced, with an enhanced pattern of rapid wash-in and slow wash-out. Four lesions (21.05%) showed an enlarged scope in the CEUS image compared with the grayscale ultrasound image. In conclusion, an ill-defined heterogeneous hyperechoic appearance with fusiform-shaped and "fascial tail" signs on US and heterogeneous hyperenhancement with an enlarged scope on CEUS are valuable clues in the diagnosis and treatment of superficial DF. [ABSTRACT FROM AUTHOR]

Active tumor penetration has been recently recognized as a promising strategy to resolve the limitation of nanomedicine in terms of tumor penetration, but it is challenging to develop active transporting nanocarriers. Here, an ultrasonic cavitation‐assisted and acid‐activatable active transporting liposome for a broad range of tumors is reported. The active transporting liposome (size and charge dual‐conversional gemcitabine prodrug‐integrated liposomal nanodroplet (SCGLN)) overcomes the tight blood vessel walls with the aid of ultrasonic cavitation. The SCGLN subsequently transforms from micro‐size to nano‐size under prolonged ultrasound radiation. Once in the acidic tumor microenvironment, the nanosized SCGLN undergoes negative‐to‐positive charge‐reversal and triggers the cationization‐initiated transcytosis to penetrate deep into tumor parenchyma. The gemcitabine‐loaded SCGLN exhibits potent antitumor activity in multiple poorly permeable tumor models, which completely erases subcutaneous U251 glioma and stops the progression of orthotopic BxPC3 pancreatic ductal adenocarcinoma. This study presents a promising and universal strategy to develop active penetrating nanomedicines for efficient drug delivery in the low permeable tumor. [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]

Purposes: To establish a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging and reporting and data system (CEUS LI-RADS) for estimation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods: In the retrospective study, 127 HCC patients from two hospitals were allocated as training cohort (n=98) and test cohorts (n=29) based on cutoff time-point, June 2020. Multivariate regression analysis was performed to identify independent indicators for developing predictive nomogram models. The area under receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. Corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared. Results: In the training cohort, clinical information (larger tumor size, higher AFP level) and CEUS LR-M were significantly correlated with the presence of MVI (all p<0.05). By incorporating clinical information and CEUS LR-M, the predictive model (LR-M+Clin) achieved a desirable diagnostic performance (AUC=0.80 and 0.84) in both cohorts at nomogram cutoff score value of 89. The sensitivity of LR-M+Clin when predicting MVI in HCC patients was higher than that of the clinical model alone (86.7% vs. 46.7%, p=0.027), while specificities were 78.6% and 85.7% (p=0.06), respectively, in the test cohort. In addition, LR-M+Clin exhibited similar AUC and specificity, but a significantly higher sensitivity (86.7%) than those of LR-M alone and LR-5(No)+Clin (both sensitivities=73.3%, both p=0.048). Conclusion: The predictive model incorporating CEUS LR-M and clinical features was able to predict the MVI status of HCC and is a potential reliable preoperative tool for informing treatment. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) has become an established modality in various clinical indications for liver diseases. SonoVue®, a pure blood pure agent, and Sonazoid®, which exhibits an additional Kupffer phase, are contrast agents approved for liver imaging. This review discusses and compares the current clinical evidence for these two ultrasound contrast agents in the characterization and detection of focal liver lesions in the non-cirrhotic and cirrhotic liver, as well as for the use in interventional procedures such as liver biopsy guidance, and local ablation treatment monitoring. Reference is made to clinical studies which evaluated the accuracy of CEUS using a standard of reference, its safety, or to comparative studies of these two agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ultrasound often represents the first diagnostic step for thyroid nodule evaluation in clinical practice, but baseline US alone is not always effective enough to achieve thyroid nodule characterization. In the last decades new ultrasound techniques, such as CEUS, have been introduced to evaluate thyroid parenchyma as recommended by EFSUMB guidelines, for use in clinical research field, although its role is not yet clear. Several papers show the potential utility of CEUS in the differential diagnosis of benign and malignant thyroid nodules and in the analysis of lymph node involvement in neoplastic pathology. Therefore, we carried out an evaluation of the literature concerning the role of CEUS in three specific areas: the characterization of the thyroid nodule, the evaluation of minimally invasive treatment and loco-regional staging of the lymph node in proven thyroid cancer. According to evidence reported, CEUS can also play an operative role in nodular thyroid pathology as it is able to guide ablation procedures on thyroid nodule and metastatic lymph nodes, to assess the radicality of surgery, to evaluate disease relapse at the level of the margins of ablated regions and to monitor the clinical evolution of necrotic areas in immediate post-treatment setting. [ABSTRACT FROM AUTHOR]

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]

• Breakthrough nanoparticle to distinguish hemorrhagic plaque from other vulnerable plaques via ultrasound, photoacoustic, and magnetic resonance multimodality imaging. • Effective strategy to fill the gap of treatment about intraplaque hemorrhage. • Novel strategy for early diagnosis and visualized treatment of intraplaque hemorrhage. Intraplaque hemorrhage (IPH) is a critical contributor to atherosclerotic plaque progression and destabilization; however, its timely detection and treatment of IPH are limited. In this study, novel macrophage-targeted nanoparticles (NPs) are developed that encapsulate perfluoropentane (PFP) in the core, load MnFe 2 O 4 and ferrostatin-1 (Fer-1) in the polylactic acid-glycolic acid (PLGA) shell, and conjugate CTHRSSVVC peptide on the surface. These NPs exhibit highly sensitive and specific magnetic resonance/photoacoustic/ultrasound multimodal imaging to distinguish the hemorrhagic plaque from other vulnerable plaques accurately. Further, the distribution could be observed in real-time, conducive to individual visualized therapy. The NPs could actively target the M(Hb) cell, which plays a critical role in clearing erythrocyte lysed products within IPH area. Additionally, Fer-1 loaded in the NPs exhibits a controlled release with non-invasive low-intensity focused ultrasound and further rescues the M(Hb) ferroptosis due to overloaded hemoglobin by scavenging lipid peroxides and chelating iron directly, subsequently stabilizing the hemorrhagic plaque without any toxic biological effects. Overall, these intricately designed NPs introduce a safe and effective theranostic strategy for IPH in susceptible populations, which is promising for further clinical applications. [ABSTRACT FROM AUTHOR]

Adenosis is a benign breast condition whose lesions can mimic breast carcinoma and is evaluated for malignancy with the Breast Imaging–Reporting and Data System (BI-RADS). We construct and validate the performance of modality-specific enhancement (MSE)-Breast Net based on multimodal ultrasound images and compare it to the BI-RADS in differentiating adenosis from breast cancer. A total of 179 patients with breast carcinoma and 229 patients with adenosis were included in this retrospective, two-institution study, then divided into a training cohort (institution I, n = 292) and a validation cohort (institution II, n = 116). In the training cohort, the final model had a significantly greater AUC (0.82; P < 0.05) than B-mode–based model (0.69, 95% CI [0.49–0.90]). In the validation cohort, the AUC of the final model was 0.81, greater than that of the BI-RADS (0.75, P < 0.05). The multimodal model outperformed the individual and bimodal models, reaching a significantly greater AUC of 0.87 (95% CI = 0.69–1.0) (P < 0.05). MSE-Breast Net, based on multimodal ultrasound images, exhibited better diagnostic performance than the BI-RADS in differentiating adenosis from breast cancer and may contribute to clinical diagnosis and treatment. • Guiding the development of clinical treatment strategies has proven challenging due to the distinct treatment approaches used for adenosis and invasive carcinoma. • MSE aims to improve the quality of images obtained from a particular imaging modality by taking into account its specific characteristics and optimizing the enhancement process to better suit the modality. • We established a model-MSE-Breast Net, based on multimodal ultrasound images to distinguish adenosis from cancer and evaluate its ability to differentiate adenosis from breast carcinoma. • MSE-Breast Net, based on multimodal ultrasound images, exhibited better diagnostic performance than the BI-RADS in differentiating adenosis from breast cancer. [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]

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]

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]