Doping-Engineered Piezoelectric Ultrathin Nanosheets for Synergistically Piezo-Chemocatalytic Antitumor and Antibacterial Therapies Against Cutaneous Melanoma.

The post-surgical melanoma recurrence and wound infections have persistently troubled clinical management. Piezocatalytic therapy features high efficiency in generating reactive oxygen species (ROS) for tumor therapy, but it faces limitations in piezoelectricity and redox-active site availability. Herein, Fe-doped ultrathin Bi4Ti3O12 nanosheets (designated as Fe-UBTO NSs) with synergistically piezo-chemocatalytic activity are engineered for antitumor and antibacterial treatment against cutaneous melanoma. The doping-engineered strategy induces oxygen vacancies and lattice distortions in Fe-UBTO NSs, which narrows bandgap to enhance piezocatalytic 1O2 and H2O2 generation by improving the electron-hole pairs separation, hindering their recombination, and increasing oxygen adsorption. Moreover, Fe doping establishes a piezo-chemocatalytic system, in which the piezocatalysis enables the self-supply of H2O2 and expedites electron transfer in Fenton reactions, inducing increased ·OH production. Besides, the atomic-level thickness and expanded surface area enhance the sensitivity to ultrasound stimuli and expose more redox-active sites, augmenting the piezo-chemocatalytic efficiency, and ultimately leading to abundant ROS generation. The Fe-UBTO-mediated piezo-chemocatalytic therapy causes intracellular oxidative stress, triggering apoptosis and excessive autophagy of tumor cells. Moreover, this strategy accelerates wound healing by facilitating sterilization, angiogenesis, and collagen deposition. This work provides distinct options to develop doping-engineered ultrathin nanosheets with augmented piezo-chemocatalytic activity for postoperative management of cutaneous melanoma.

Differentiating Benign From Malignant Ovarian Masses With Solid Components: Diagnostic Performance of CEUS Combined With IOTA Simple Rules and O-RADS.

OBJECTIVE: This study aimed to apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Ovarian-Adnexal Reporting and Data System (O-RADS) and contrast-enhanced ultrasound (CEUS) in an identical cohort of Chinese patients and to analyze their performance in discrimination of ovarian masses with solid components. METHODS: This was a two-center retrospective study that included a total of 94 ovarian lesions in 86 women enrolled from January 2018 to February 2023. The lesions were classified by using the IOTA terminology and CEUS was performed for the lesions exhibiting solid components on ultrasonography, IOTA SR and O-RADS were applied, and CEUS images were analyzed retrospectively. We assessed the time to wash-in, time to peak intensity (PI), PI compared to myometrium, and time to wash-out, and observed statistically significant differences between benign and malignant lesions in the first three parameters. CEUS characteristics were employed to determine CEUS scores for benign (score 0) and malignant (score 3) lesions. Subsequently, the lesions were reassessed based on the IOTA SR and O-RADS classifications and CEUS scores. The sensitivity, specificity, and area under the receiver-operating-characteristics curve (AUC) of the different models were also determined. RESULTS: Among the 94 ovarian lesions, 46 (48.9%) were benign and 48 (51.1%) were malignant. It was found that in the 60 lesions to which the SR could be applied, the sensitivity, specificity, and AUC was 0.900, 0.667, and 0.783, respectively. The sensitivity, specificity, and AUC of O-RADS was observed to be 1.000, 0.283 and 0.641, respectively. When SR and O-RADS were combined with CEUS, their sensitivity, specificity, and AUC values were increased to 0.917, 0.891, 0.904, and 0.958, 0.783, 0.871, respectively. CONCLUSION: IOTA SR and O-RADS exhibited relatively low specificity in differentiating malignant from benign ovarian lesions with the solid components, and their diagnostic performance can be significantly improved when combined with CEUS.

Development and validation of a clinical and ultrasound features-based nomogram for preoperative differentiation of renal urothelial carcinoma and central renal cell carcinoma.

PURPOSE: This study aimed to develop and validate an ultrasound (US)-based nomogram for the preoperative differentiation of renal urothelial carcinoma (rUC) from central renal cell carcinoma (c-RCC). METHODS: Clinical data and US images of 655 patients with 655 histologically confirmed malignant renal tumors (521 c-RCCs and 134 rUCs) were collected and divided into training (n = 455) and validation (n = 200) cohorts according to examination dates. Conventional US and contrast-enhanced US (CEUS) tumor features were analyzed to determine those that could discriminate rUC from c-RCC. Least absolute shrinkage and selection operator regression was applied to screen clinical and US features for the differentiation of rUC from c-RCC. Using multivariate logistic regression analysis, a diagnostic model of rUC was constructed and visualized as a nomogram. The diagnostic model's performance was assessed in the training and validation cohorts by calculating the area under the receiver operating characteristic curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness of the US-based nomogram. RESULTS: Seven features of both clinical features and ultrasound imaging were selected to build the diagnostic model. The nomogram achieved favorable discrimination in the training (AUC = 0.996, 95% CI: 0.993-0.999) and validation (AUC = 0.995, 95% CI: 0.974, 1.000) cohorts, and good calibration (Brier scores: 0.019 and 0.016, respectively). DCA demonstrated the clinical usefulness of the US-based nomogram. CONCLUSION: A noninvasive clinical and US-based nomogram combining conventional US and CEUS features possesses good predictive value for differentiating rUC from c-RCC.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Automated Breast Volume Scanner Is More Valuable Than Hand-Held Ultrasound in Diagnosis of Small Breast cancer: An Analysis of 725 Patients With 912 Lesions Evaluations.

ABSTRACT: This study aimed to evaluate the clinical value of automated breast volume scanner (ABVS) compared with hand-held ultrasound (HHUS). From January 2015 to May 2019, a total of 912 breast lesions in 725 consecutive patients were included in this study. κ statistics were calculated to identify interobserver agreement of ABVS and HHUS. The diagnostic performance for ABVS and HHUS was expressed as the area under the receiver operating characteristic curve, as well as the corresponding 95% confidence interval, sensitivity, and specificity. The sensitivities of ABVS and HHUS were 95.95% and 93.69%, and the specificities were 85.47% and 81.20%, respectively. A difference that nearly reached statistical significance was observed in sensitivities between ABVS and HHUS (P = 0.0525). The specificity of ABVS was significantly higher than that of HHUS (P = 0.006). When lesions were classified according to their maximum diameter, the sensitivity and specificity of ABVS were significantly higher than HHUS for lesions ≤20 mm, while they made no statistical significance between ABVS and HHUS for lesions >20 mm. The interobserver agreement for ABVS was better than that of HHUS. Automated breast volume scanner was more valuable than HHUS in diagnosing breast cancer, especially for lesions ≤20 mm, and it could be a valuable diagnostic tool for breast cancer.

Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization.

The infiltration of inflammatory cells, especially macrophages, integrated with the production of reactive oxygen and nitrogen species (RONS) and the release of inflammatory cytokines play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Synergistic combination of RONS scavenging and macrophage repolarization from pro-inflammatory M1 phenotype towards anti-inflammatory M2 phenotype, provides a promising strategy for efficient RA treatment. Herein, this study reported a unique self-assembly strategy to construct distinct rosmarinic acid nanoparticles (RNPs) for efficient RA treatment using the naturally occurring polyphenol-based compound, rosmarinic acid (RosA). The designed RNPs exhibited favorable capability in scavenging RONS and pro-inflammatory cytokines produced by macrophages. Attributing to the widened vascular endothelial-cell gap at inflammation sites, RNPs could target and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats for guaranteeing therapeutic effect. In vivo investigation demonstrated that RNPs alleviated the symptoms of RA, including joint swelling, synovial hyperplasia, cartilage degradation, and bone erosion in CIA rats. Additionally, the designed RNPs promoted macrophage polarization from M1 phenotype towards M2 phenotype, resulting in the suppressed progression of RA. Therefore, this research represents the representative paradigm for RA therapy using antioxidative nanomedicine deriving from the natural polyphenol-based compound.

Ultrasound-Triggered Cascade Amplification of Nanotherapy.

Ultrasound (US)-triggered cascade amplification of nanotherapies has attracted considerable attention as an effective strategy for cancer treatment. With the remarkable advances in materials chemistry and nanotechnology, a large number of well-designed nanosystems have emerged that incorporate presupposed cascade amplification processes and can be activated to trigger therapies such as chemotherapy, immunotherapy, and ferroptosis, under exogenous US stimulation or specific substances generated by US actuation, to maximize antitumor efficacy and minimize detrimental effects. Therefore, summarizing the corresponding nanotherapies and applications based on US-triggered cascade amplification is essential. This review comprehensively summarizes and highlights the recent advances in the design of intelligent modalities, consisting of unique components, distinctive properties, and specific cascade processes. These ingenious strategies confer unparalleled potential to nanotherapies based on ultrasound-triggered cascade amplification and provide superior controllability, thus overcoming the unmet requirements of precision medicine and personalized treatment. Finally, the challenges and prospects of this emerging strategy are discussed and it is expected to encourage more innovative ideas and promote their further development.

Comparison of contrast-enhanced ultrasound, IOTA simple rules and O-RADS for assessing the malignant risk of sonographically appearing solid ovarian masses.

PURPOSE: To explore the diagnostic accuracy of ovarian solid tumors by 2D ultrasound and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: We retrospectively evaluated the CEUS characteristics of prospectively enrolled 16 benign and 19 malignant ovarian solid tumors. We performed International Ovarian Tumor Analysis (IOTA) simple rules and Ovarian-Adnexal Reporting and Data System (O-RADS) for all lesions, and evaluated their characteristics on CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of IOTA simple rules, O-RADS and CEUS in the diagnosis of ovarian solid malignancies were calculated. RESULTS: The combination of time to wash-in earlier than or equal to the myometrium, time to PI earlier than or equal to the myometrium and the intensity at peak were higher than or equal to myometrium with sensibility of 0.947, specificity of 0.938, and PPV of 0.947, NPV of 0.938 which were higher than IOTA simple rules and O-RADS. According to the definition of ovarian solid tumor, the diagnostic accuracy of O-RADS 3 and CEUS were both 100%, CEUS improved the accuracy of O-RADS 4 from 47.4% to 87.5%, the accuracy of solid smooth CS 4 in O-RADS 5 and CEUS were both 100%, CEUS improved the accuracy of solid irregular in O-RADS 5 from 70% to 87.5%. CONCLUSION: For ovarian solid tumors that are difficult to distinguish between benign and malignant, the introduction of CEUS on the basis of 2D classification criteria can significantly improve the diagnostic accuracy.

The Preliminary Application of Simultaneous Display of Contrast-Enhanced Ultrasound and Micro-Flow Imaging Technology in the Diagnosis of Hepatic Tumors.

OBJECTIVES: To evaluate the value of simultaneous display of contrast-enhanced ultrasound and micro-flow imaging technology (CEUS-MFI) in intra-tumoral vessel detection and hepatic tumor diagnosis. METHODS: A total of 82 patients with 82 focal liver lesions were enrolled in this study. Each patient received ultrasound exams including color Doppler flow imaging (CDFI), micro-flow imaging (MFI), contrast-enhanced ultrasound (CEUS), and CEUS-MFI with a Philips EPIQ7 ultrasound imaging system. The intra-tumoral vessels detected by CDFI, MFI, and CEUS-MFI were compared, respectively. The accuracy and confidence of using CEUS and CEUS-MFI in diagnosing hepatic tumors were also compared. RESULTS: CEUS-MFI was capable of detecting more hepatic intra-tumoral vessels than MFI (P = .000) and CDFI (P = .000). Compared with CEUS, CEUS-MFI improved the diagnostic accuracy of hepatic lesions (P = .009). Particularly, among the correctly diagnosed hepatic lesions, the number of cases where radiologists diagnosed with great confidence was increased from 88.4% (61/69) with CEUS only to 92.4% (73/79) with CEUS-MFI (P = .041). CONCLUSIONS: CEUS-MFI is sensitive in detecting hepatic intra-tumoral vessels and can improve the accuracy and confidence of radiologists in diagnosing hepatic lesions.

3D-CEUS tracking of injectable chemo-sonodynamic therapy-enabled mop-up of residual renal cell carcinoma after thermal ablation.

Thermal ablation (TA), as a minimally invasive therapeutic technique, has been extensively used to the treatment of solid tumors, such as renal cell carcinoma (RCC), which, unfortunately, still fails to overcome the high risk of local recurrence and distant metastasis since the incomplete ablation cannot be ignored due to various factors such as the indistinguishable tumor margins and limited ablation zone. Herein, we report the injectable thermosensitive hydrogel by confining curcumin (Cur)-loaded hollow mesoporous organosilica nanoparticles (Cur@HMON@gel) which can locate in tumor site more than half a month and mop up the residual RCC under ultrasound (US) irradiation after transforming from colloidal sol status to elastic gel matrix at physiological temperature. Based on the US-triggered accelerated diffusion of the model chemotherapy drug with multi-pharmacologic functions, the sustained and controlled release of Cur has been demonstrated in vitro. Significantly, US is employed as an external energy to trigger Cur, as a sonosensitizer also, to generate reactive oxygen species (ROS) for sonodynamic tumor therapy (SDT) in parallel. Tracking by the three-dimensional contrast-enhanced ultrasound (3D-CEUS) imaging, the typical decreased blood perfusions have been observed since the residual xenograft tumor after incomplete TA were effectively suppressed during the chemo-sonodynamic therapy process. The high in vivo biocompatibility and biodegradability of the multifunctional nanoplatform confined by thermogel provide the potential of their further clinical translation for the solid tumor eradication under the guidance and monitoring of 3D-CEUS.

Blood Perfusion Characteristics of Renal Cell Carcinoma in the Process of Tumor Growth: Monitored With Multiple Sonographic Modalities.

ABSTRACT: Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter ( d ), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mm < d ≤ 10 mm, and d > 10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d > 10 mm than those d < 10 mm ( P < 0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P < 0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI ( P < 0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those >10 mm ( P < 0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.

Quantitative Indicators of Retraction Phenomenon on an Automated Breast Volume Scanner: Initial Study in the Diagnosis and Prognostic Prediction of Breast Tumors.

Retraction phenomenon is a unique sign on an automated breast volume scanner coronal plane image and has high specificity in differentiating benign lesions from malignant breast cancer. The purpose of this study was to quantify the retraction phenomenon by setting different rules to describe connected regions from different dimensions. In total, six quantitative indicators (FΩ1,FΓ,FS,FΩ2,FΩ3and FL) were obtained. FΩ1, FΩ2 and FΩ3 represent the relative areas of the connected region under different rules. FΓandFS represent the number ratio and absolute area of the connected region, respectively. FL represents the ratio of edge numbers. Two hundred fourteen patients with 214 lesions (90 benign and 124 malignant) were enrolled in this study. All quantitative indicators in the malignant group were significantly higher than those in the benign group (all p values <0.001). The indicator FΓ achieved the highest area under the receiver operating characteristic curve (AUC) (0.701, 95% confidence interval: 0.631-0.771). Both FΓ and FS had significant associations with axillary lymph node metastasis (p = 0.023 and 0.049). Compared with the classic texture feature gray-level co-occurrence matrix, retraction phenomenon quantization improved the AUC by 8.3%. The results indicate that retraction phenomenon quantitative indicators have certain value in distinguishing benign and malignant breast lesions and seem to be associated with axillary lymph node metastasis.

Prediction of Microvascular Invasion in Combined Hepatocellular-Cholangiocarcinoma Based on Pre-operative Clinical Data and Contrast-Enhanced Ultrasound Characteristics.

The goal of the study described here was to define the predictive value of pre-operative clinical information and contrast-enhanced ultrasound (CEUS) imaging characteristics in combined hepatocellular-cholangiocarcinoma (CHC) patients with microvascular invasion (MVI). Seventy-six patients with pathologically confirmed CHC were enrolled in this study, comprising 18 patients with MVI-positive status and 58 with MVI-negative CHC nodules. The pre-operative clinical data and CEUS imaging features were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the potential predictors of MVI in CHC. Recurrence-free survival (RFS) after hepatectomy was compared between patients with different MVI status using the log-rank test and Kaplan-Meier survival curves. Univariate analysis indicated that the following parameters of patients with CHC significantly differed between the MVI-positive and MVI-negative groups (p<0.05): tumor size, α-fetoprotein ≥400 ng/mL, enhancement patterns in arterial phase and marked washout during the portal venous phase on CEUS. On multivariate logistic regression analysis, only the CEUS characteristics of heterogeneous enhancement (odds ratio = 6.807; 95% confidence interval [CI]: 1.099, 42.147; p = 0.039) and marked washout (odds ratio = 4.380; 95% CI: 1.050,18.270; p = 0.043) were identified as independent predictors of MVI in CHC. The combination of the two risk factors in predicting MVI achieved a better diagnostic performance than each parameter alone, with an area under the receiver operating characteristic curve of 0.736 (0.622, 0.830). After hepatectomy, CHC patients with MVI exhibited earlier recurrence compared with those without MVI (hazard ratio = 1.859; 95% CI: 0.8699-3.9722, p = 0.046). The CEUS imaging features of heterogeneous enhancement in the arterial phase and marked washout during the portal venous phase were the potential predictors of MVI in CHC. Aside from that, CHC patients with MVI had an earlier recurrence rate than those without MVI after surgery.

Sequential Ultrasound-Triggered and Hypoxia-Sensitive Nanoprodrug for Cascade Amplification of Sonochemotherapy.

Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT2-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT2-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT2-Azo prodrug was released from the MOF NPs. Under US actuation, this sonochemotherapeutic nanoprodrug not only promoted sonosensitizer-mediated sonodynamic therapy (SDT) via the conversion of oxygen into cytotoxic reactive oxygen species (ROS) but also aggravated hypoxia in the TME by elevating oxygen consumption. The exacerbated hypoxia in turn served as a positive amplifier to boost the activation of CPT2-Azo, and the controllable release of toxic chemotherapeutic drug (CPT), and compensated the insufficient treatment efficacy of SDT. In vitro and in vivo evaluations confirmed that sequential SDT and tumor hypoxia-activated sonochemotherapy promoted the utmost of tumor hypoxia and thereby contributed to the augmented antitumor efficacy, resulting in conspicuous apoptotic cell death and noteworthy tumor suppression in vivo. Our work provides a distinctive insight into the exploitation of the hypoxia-activated sonochemotherapeutic nanoprodrug that utilizes the hypoxic condition in TME, a side effect of SDT, to initiate chemotherapy, thus causing a significantly augmented treatment outcome compared to conventional SDT.

Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy.

Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe2 O4 @CoFe2 O4 , denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen-irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer-cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen-irrelevant nanoplatform for AMF-initiated synergistic cancer treatment.

Early evaluation of treatment response to transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The role of dynamic three-dimensional contrast-enhanced ultrasound.

BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1-3 days (T1) after treatment. Tumor microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients.

The value of ultrasonography combined with clinical features for predicting carotid imaging progression of Takayasu's arteritis: a prospective cohort study.

OBJECTIVES: To identify valuable ultrasonography findings combined with clinical markers for predicting carotid progression of Takayasu's arteritis (TAK) on imaging during a 1-year follow-up period. METHODS: From May 2016 to June 2019, 77 Chinese TAK patients with carotid artery involvement were enrolled in the present study. The patients' clinical characteristics and serological test and carotid ultrasonography results were recorded at baseline and each visit. Carotid progression was evaluated by ultrasonography every 3 months during the 1-year follow-up. Baseline clinical characteristics and ultrasonography results for predicting progression on imaging were identified. RESULTS: Sixteen (20.8%) patients presented with carotid progression on imaging during the 1-year follow-up period. The patients in the progressive group were younger (23.4±3.7 vs. 32.3±9.8 years, p<0.01) than those in the non-progressive group. At baseline, the vessel wall was thicker in the progressive group than in the non-progressive group (2.4±0.8 vs. 1.9±0.5 mm, p=0.041). Furthermore, the proportion of patients with refractory disease (87.5% vs. 16.4%, p<0.01) was higher in the progressive group than in the non-progressive group. Patients with a thickened carotid wall (≥1.9 mm), refractory disease, and younger age (≤30 years) might be at a high risk of carotid progression on imaging (75%, AUC: 0.93, sensitivity: 75%, specificity: 93.4%). CONCLUSIONS: Younger patients with early vascular structural changes at baseline as well as refractory disease seemed more likely to show carotid progression on imaging.

Risk factors of ultrasound-detected tophi in patients with gout.

INTRODUCTION: Tophus is a characteristic manifestation of advanced gout, the clinical significance of which is often underestimated. This study aimed to compare the difference of clinical and ultrasound features between gout patients with and without ultrasound-detected tophus and identify risk factors associated with the presence of ultrasonographic tophus in gout patients. MATERIALS AND METHODS: A total of 85 gout patients were divided into tophaceous (n = 54) and non-tophaceous group (n = 31) according to the presence of ultrasound-detected tophus. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joint (MTP1). Clinical information and ultrasound findings were compared between the groups. A multivariate logistic regression analysis to determine possible risk factors is associated with the number of ultrasound-detected tophaceous joints. RESULTS: Older age, longer gout duration, higher gout flare frequency, lower estimated glomerular filtration rate (eGFR), and higher prevalence of hypertension, hyperlipidemia, and ultrasound manifestations including double contour sign (DCS) and erosion were observed in tophaceous patients from the univariate analysis. Multivariable logistic regression analysis showed that eGFR and disease duration were independently associated with the number of tophaceous joints. Lower eGFR and longer course duration were associated with a higher risk of tophi (B = -0.020, 0.141; P = 0.009, 0.010, respectively). CONCLUSIONS: The main factors that may influence the formation of tophi are disease duration and eGFR.Key Points• Lower eGFR and longer course duration are independent risk factors of tophi formation in gout patients.• The incidence of ultrasound manifestations including double contour sign (DCS) and erosion in patients with tophi were higher than those without tophi.

Assessment of Metastatic and Reactive Sentinel Lymph Nodes with B7-H3-Targeted Ultrasound Molecular Imaging: A Longitudinal Study in Mouse Models.

PURPOSE: To explore the potential of B7-H3-targeted ultrasound molecular imaging (USMI) for longitudinal assessment and differentiation of metastatic and reactive sentinel lymph nodes (SLNs) in mouse models. PROCEDURES: Metastatic and reactive SLN models were established by injection of 4T1 breast cancer cells and complete Freund's adjuvant (CFA) respectively to the 4th mammary fat pad of female BALB/c mice. At day 21, 28, and 35 after inoculation, USMI was performed following intravenous injection of B7-H3-targeted microbubbles (MBB7-H3) or IgG-control microbubbles (MBcontrol). All SLNs were histopathologically examined after the last imaging session. RESULTS: A total of 20 SLNs from tumor-bearing mice (T-SLNs) and five SLNs from CFA-injected mice (C-SLNs) were examined by USMI. Nine T-SLNs were histopathologically positive for metastasis (MT-SLNs). From day 21 to 35, T-SLNs showed a rising trend in MBB7-H3 signal with a steep increase in MT-SLNs at day 35 (213.5 ± 80.8 a.u.) as compared to day 28 (87.6 ± 77.2 a.u., P = 0.002) and day 21 (55.7 ± 35.5 a.u., P < 0.001). At day 35, MT-SLNs had significantly higher MBB7-H3 signal than non-metastatic T-SLNs (NMT-SLNs) (101.9 ± 48.0 a.u., P = 0.001) and C-SLNs (38.5 ± 34.0 a.u., P = 0.001); MBB7-H3 signal was significantly higher than MBcontrol in MT-SLNs (P = 0.001), but not in NMT-SLNs or C-SLNs (both P > 0.05). A significant correlation was detected between MBB7-H3 signal and volume fraction of metastasis in MT-SLNs (r = 0.76, P = 0.017). CONCLUSIONS: B7-H3-targeted USMI allows differentiation of MT-SLNs from NMT-SLNs and C-SLNs in mouse models and has great potential to evaluate tumor burden in SLNs of breast cancer.

Sex-specific association of metabolic risk factors with brain ischemic lesions by severity and location.

BACKGROUND: Males and females exhibit significant differences in metabolism and in brain ischemic stroke and different features of brain ischemic lesions are related to different health outcomes. It is critical to understand sex differences in their associations to optimize prevention and intervention for both sexes. We aimed to investigate the sex-specific association of metabolic risk factors with brain ischemic lesions by severity and location. METHODS: Five thousand seven hundred ninety-one participants who underwent comprehensive health examinations between Jan. 1, 2017, and Dec. 31, 2017, were enrolled. Clinical and laboratory data about metabolic risk factors were obtained. Brain ischemic lesions were further categorized by severity (mild ischemic lesions or severe infarct lesions) and location (strictly lobar or deep brain/infratentorial areas) based on brain magnetic resonance imaging reports. Sex- and age-specific detected rates were calculated, and generalized linear models and multinomial logistic regression were used to analyze the associations between metabolic risk factors and the presence, severity, and location of ischemic lesions stratified by sex. RESULTS: A total of 2712 (46.8%) participants had at least one brain ischemic lesions. Age (adjusted OR, 1.10 [1.10-1.11], p < 0.001) and hypertension (adjusted OR, 1.42 [1.22-1.64], p < 0.001) were generally associated with higher risks of brain ischemia in both sexes. Metabolic syndrome was associated with greater adjusted ORs for brain ischemia with different severity and location in men (adjusted ORs between 1.23 and 1.49) but not in women. Overweight and obesity were related to lesions located strictly in lobar in men (adjusted OR, 1.23 and 1.33, respectively) and lesions located in deep brain/infratentorial areas in women (adjusted OR, 1.57 and 2.26, respectively). CONCLUSIONS: Metabolic syndrome was associated with brain ischemic lesions in men but not in women. Higher body mass index was related to ischemic lesions located in lobar in men and in deep brain/infratentorial areas in women. Its mechanisms remain to be further investigated.