Feeding artery: a valuable feature for differentiation of regenerative nodule, dysplastic nodules and small hepatocellular carcinoma in CEUS LI-RADS.

OBJECTIVE: To investigate whether the feeding artery (FA) feature can aid in discriminating small hepatocellular carcinoma (HCC) using the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) from precancerous lesions. METHODS: Between June 2017 and May 2021, a total of 347 patients with 351 precancerous liver lesions or small HCCs who underwent CEUS were enrolled. Two independent radiologists assigned LI-RADS categories to all lesions and assessed the presence of the FA feature, which was used as an ancillary feature to either upgrade or downgrade the LI-RADS category. The diagnostic performance of CEUS LI-RADS, both with and without the FA feature, was evaluated based on accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The FA feature was found to be more prevalent in HCC (85.54%, p < 0.001) than in regenerative nodules (RNs, 29.73%), low-grade dysplastic nodules (LGDNs, 33.33%), and high-grade dysplastic nodules (HGDNs, 55.26%). Furthermore, the presence of arterial phase hyperenhancement (APHE), washout (WO), and FA in liver nodules was associated with a higher expression of GPC-3 and Ki-67 compared to the group without these features (p < 0.001). After adjusting, the sensitivity and accuracy of LR-5 for HCC improved from 68.67% (95%CI: 62.46%, 74.30%) to 77.51% (95%CI: 71.72%, 82.44%) and from 69.23% (95%CI: 64.11%, 74.02%) to 73.79% (95%CI: 68.86%, 78.31%), respectively. CONCLUSION: The FA feature is a valuable feature for distinguishing small HCC and precancerous lesions and could be added as a possible ancillary feature in CEUS LI-RADS which was backed up by biomarkers. CLINICAL RELEVANCE STATEMENT: The presence of a feeding artery is a valuable imaging feature in the differentiation of HCC and precancerous lesions. Incorporating this characteristic in the CEUS LI-RADS can enhance the diagnostic ability. KEY POINTS: • Feeding artery is more frequent in HCC than in regenerative nodules, low-grade dysplastic nodules, and high-grade dysplastic nodules. • Feeding artery feature is a valuable ancillary feature for CEUS LI-RADS to differentiate regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, and HCC. • The existence of feeding artery, arterial phase hyperenhancement, and washout is associated with more GPC-3 positive expression and higher Ki-67 expression than the group without these features.

Safety and efficacy of microwave ablation for symptomatic benign thyroid nodules in children.

OBJECTIVE: To evaluate the efficacy and safety of microwave ablation (MWA) for the treatment of symptomatic benign thyroid nodules in children. METHODS: A retrospective study of MWA for the treatment of 34 symptomatic benign thyroid nodules in 25 children was conducted. Volume reduction ratio (VRR), technique efficacy, symptom score, cosmetic score, and thyroid function were used to evaluate the efficacy of the technique. The associated complications and side effects were recorded. RESULTS: The participants were followed for at least 6 months (median 12 months, range 6-48 months). After MWA treatment, the volumes of the targeted nodules decreased gradually (median volume 5.86 mL before MWA and 0.34 mL at the final follow-up assessment), the VRR achieved was up to 85.03% at the final follow-up assessment, and the technical efficacy at this time was 91.2%. The subjective and objective nodule-related symptoms were also ameliorated. The circulating hormone concentrations reflecting thyroid function remained within their normal ranges in all the participants after one month of follow-up. The procedure had no major complications. CONCLUSIONS: MWA seems to be an effective and safe technique for the treatment of symptomatic benign thyroid nodules in pediatric patients. CLINICAL RELEVANCE STATEMENT: Microwave ablation is a safe and effective method to treat symptomatic benign thyroid nodules in pediatric patients. This treatment may be selected if the patient or parents are not suitable or refuse to undergo surgery. KEY POINTS: • Microwave ablation is effective in reducing the volume of benign thyroid nodules and ameliorating nodule-related symptoms in pediatric patients. • Microwave ablation is a safe method in children, with low complications. • Microwave ablation does not affect the circulating thyroid hormone concentrations of children.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes.

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

Prognostic and pathological implications of contrast-enhanced ultrasound features in hepatocellular carcinoma.

Background: Contrast-enhanced ultrasound (CEUS) plays a vital role in diagnosing hepatocellular carcinoma (HCC) and, to some extent, reflects tumor prognosis. This suggests that some pathological features of HCC may be associated with CEUS features. Aim: This study aimed to verify the prognostic significance of four CEUS features and further explore their pathological significance. Materials and Methods: This study included 243 HCC patients who underwent a preoperative CEUS examination. All pathological diagnoses and immunohistochemical information were obtained from the pathological report. The prognostic significance of four CEUS features, including nodule-in-nodule architecture, mosaic architecture, intratumoral feeding arteries, and peritumoral arterial phase (AP) hyperenhancement, was analyzed. The correlation between prognostic-related features and immunohistochemical information was further analyzed. Results: The disease-free survival (DFS) of HCC was significantly affected by mosaic architecture or intratumoral feeding arteries (HR = 1.79; 95% confidence interval (95% CI), 1.09-2.95; P = 0.004; HR = 1.70; 95% CI, 1.07-2.71; P = 0.025, respectively). Intratumoral feeding arteries were positively correlated with the expression of serum alpha-fetoprotein (AFP), microvascular invasion (MVI), differentiation, size, and Ki-67, among which the correlation with size was the strongest, followed by Ki-67 and MVI. The mosaic architecture was positively correlated with serum AFP, MVI, differentiation, and size, among which the correlation with size was strongest, followed by MVI. Conclusion: The mosaic architecture and intratumoral feeding arteries of CEUS were closely related to the postoperative progression of HCC. Mosaic architecture had a good correlation with tumor size and MVI, whereas intratumoral feeding arteries were closely associated with tumor size and Ki-67 expression.

On-Site Diagnostic Ability of CEUS/CT/MRI for Hepatocellular Carcinoma (2019-2022): A Multicenter Study.

OBJECTIVES: To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS: Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS: Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS: Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.

Two-Year Choroidal Thickness Attenuation and Its Associations in Healthy Chinese Adults.

Purpose: Identifying clinical associations causing attenuation in choroidal thickness (CT) among healthy Chinese adults. Methods: A 2-year longitudinal study was conducted in volunteers aged over 30 years from China. All participants had no history of eye disease or surgery. All subjects underwent swept-source optical coherence tomography to measure the CT in the macular region at baseline and at 2-year follow-up. The regression models were based on the generalized estimating equation. Results: A total of 603 eyes of 336 healthy participants were included in the final analysis (mean [SD] age, 58.88 [8.82] years; 74.70% female). Mean (SD) choroidal thickness (MCT) was reduced significantly from 206.62 (72.42) to 194.02 (72.08) µm (difference, -12.60 µm; 95% confidence interval [CI], -13.62 to -11.57). Among the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid, CT at the subfoveal sector showed the greatest 2-year reduction (difference, -14.55 µm; 95% CI, -15.87 to -13.22). The largest 2-year change was observed in the 50 to 59 years group (difference, -14.51 µm; 95% CI, -16.71 to -12.32). Multivariate regression showed female gender (ß = -2.85; 95% CI, -5.65 to -0.56) and baseline MCT (ß = -0.040; 95% CI, -0.056 to -0.024) were significantly and independently associated with greater 2-year CT decrease. Conclusions: These results indicated that CT among Chinese healthy adults decreased during the 2-year follow-up, and the greater choroidal thinning rate was significantly associated with female gender and larger baseline MCT. Translational Relevance: Longitudinal CT data of healthy adults provide a reference range when evaluating pathologic variations, especially for the age-related retinal-choroidal disorders.

Radiomics analysis of ultrasound to predict recurrence of hepatocellular carcinoma after microwave ablation.

OBJECTIVE: To develop and validate an ultrasonic radiomics model for predicting the recurrence and differentiation of hepatocellular carcinoma (HCC). Convolutional neural network (CNN) ResNet 18 and Pyradiomics were used to analyze gray-scale-ultrasonic images to predict the prognosis and degree of differentiation of HCC. METHODS: This retrospective study enrolled 513 patients with HCC who underwent preoperative grayscale-ultrasonic imaging, and their clinical characteristics were observed. Patients were randomly divided into training (n = 413) and validation (n = 100) cohorts. CNN ResNet 18 and Pyradiomics were used to analyze ultrasonic images of HCC and peritumoral images to develop a prognostic and differentiation model. Clinical characteristics were integrated into the radiomics model and patients were stratified into high- and low-risk groups. The predictive effect was evaluated using the C-index and receiver operating characteristic (ROC) curve. RESULTS: The model combined with ResNet 18 and clinical characteristics achieved a good predictive ability. The C-indices of early recurrence (ER), late recurrence (LR), and recurrence-free survival (RFS) were 0.695 (0.561-0.789), 0.715 (0.623-0.800) and 0.721 (0.647-0.795), respectively, in the validation cohort, which was superior to the clinical model and ultrasonic semantic model. The model could stratify patients into high- and low-risk groups, which showed significant differences (p < 0.001) in ER, LR, and RFS. The area under the curve for predicting the degree of HCC differentiation was 0.855 and 0.709 in the training and validation cohorts, respectively. CONCLUSION: We developed and validated a radiomics model to predict HCC recurrence and HCC differentiation, which could also acquire pathological information in a noninvasive manner.KEY RESULTSA hepatocellular carcinoma (HCC) prognostic prediction model was developed and validated by convolutional neural network (CNN) ResNet 18-based gray-scale ultrasound (US).A differentiation of HCC prediction model was developed for preoperative prediction avoiding invasive operation.Compared with Pyradiomics, CNN ResNet was more suitable for extracting information from US images.

CEUS Versus MRI in Evaluation of the Effect of Microwave Ablation of Breast Cancer.

Percutaneous microwave ablation (MWA) is a new minimally invasive technique for breast cancer treatment. The aim of this research was to compare the differences in performance between contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) with respect to the curative effect of MWA in the treatment of breast cancer. Between 2015 and 2019, 26 patients with breast cancer underwent ultrasound-guided MWA. All patients underwent both CEUS and MRI within 3 d after ablation. If either of the two imaging modalities revealed suspicious enhancement of the ablation zone and the ultrasound-guided biopsy confirmed residual tumor in the suspicious area, supplementary MWA was applied. The diagnostic efficacy of CEUS and MRI within 3 d after ablation was evaluated based on a >6-mo follow-up of 26 patients. Two cases were diagnosed with residual tumors by ultrasound that were missed by MRI. Three cases were diagnosed with residual tumors by MRI that were missed by CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the diagnosis of complete ablation were 100%, 40%, 87.5%, 100% and 88.5%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of MRI in the diagnosis of complete ablation were 100%, 60%, 91.3%, 100% and 92.3%, respectively. Within 3 d, both CEUS and MRI can efficiently assess the efficacy of MWA of breast cancer.

Is partial ablation appropriate for benign thyroid nodules? A retrospective study with long-term follow-up after microwave ablation.

OBJECTIVE: This retrospective study aimed to investigate the efficacy and safety of partial ablation (PA) for benign thyroid nodules (BTNs) using microwave ablation (MWA) in a long-term follow-up. MATERIALS AND METHODS: Between February 2015 and April 2019, 236 patients with 236 BTNs (maximum diameter ≥2 cm) treated with ultrasound-guided MWA were enrolled. Contrast-enhanced ultrasound (CEUS) was performed within 3 d after ablation to determine whether there was residual tissue according to which the patients were assigned PA or complete ablation (CA). The volume reduction ratio (VRR) and complications were evaluated during follow-up. RESULTS: Eighty-two patients were enrolled in the PA group, and 154 were enrolled in the CA group. Both groups achieved continuous reductions in nodule volume and increases in VRR within 2 years after ablation. Although the VRR of the PA group at 4 years was lower than that of the CA group (65.54 vs. 95.08%; p<.05), PA still achieved 'technical efficacy' with a volume reduction of more than 50%. The complication and side effect rates between the two groups showed no significant difference (p>.05). CONCLUSIONS: Both PA and CA were safe and effective in reducing the volumes of BTNs in the long-term follow-up. For nodules with a large initial volume and dangerous location, PA with a small amount of residual tissue may be acceptable.

Improving B-mode ultrasound diagnostic performance for focal liver lesions using deep learning: A multicentre study.

BACKGROUND: The diagnosis performance of B-mode ultrasound (US) for focal liver lesions (FLLs) is relatively limited. We aimed to develop a deep convolutional neural network of US (DCNN-US) for aiding radiologists in classification of malignant from benign FLLs. MATERIALS AND METHODS: This study was conducted in 13 hospitals and finally 2143 patients with 24,343 US images were enrolled. Patients who had non-cystic FLLs with pathological results were enrolled. The FLLs from 11 hospitals were randomly divided into training and internal validations (IV) cohorts with a 4:1 ratio for developing and evaluating DCNN-US. Diagnostic performance of the model was verified using external validation (EV) cohort from another two hospitals. The diagnosis value of DCNN-US was compared with that of contrast enhanced computed tomography (CT)/magnetic resonance image (MRI) and 236 radiologists, respectively. FINDINGS: The AUC of ModelLBC for FLLs was 0.924 (95% CI: 0.889-0.959) in the EV cohort. The diagnostic sensitivity and specificity of ModelLBC were superior to 15-year skilled radiologists (86.5% vs 76.1%, p = 0.0084 and 85.5% vs 76.9%, p = 0.0051, respectively). Accuracy of ModelLBC was comparable to that of contrast enhanced CT (both 84.7%) but inferior to contrast enhanced MRI (87.9%) for lesions detected by US. INTERPRETATION: DCNN-US with high sensitivity and specificity in diagnosing FLLs shows its potential to assist less-experienced radiologists in improving their performance and lowering their dependence on sectional imaging in liver cancer diagnosis.

Development of a deep learning model for classifying thymoma as Masaoka-Koga stage I or II via preoperative CT images.

BACKGROUND: Accurate thymoma staging via computed tomography (CT) images is difficult even for experienced thoracic doctors. Here we developed a preoperative staging tool differentiating Masaoka-Koga (MK) stage I patients from stage II patients using CT images. METHODS: CT images of 174 thymoma patients were retrospectively selected. Two chest radiologists independently assessed the images. Variables with statistical differences in univariate analysis were adjusted for age, sex, and smoking history in multivariate logical regression to determine independent predictors of the thymoma stage. We established a deep learning (DL) 3D-DenseNet model to distinguish the MK stage I and stage II thymomas. Furthermore, we compared two different methods to label the regions of interest (ROI) in CT images. RESULTS: In routine CT images, there were statistical differences (P<0.05) in contour, necrosis, cystic components, and the degree of enhancement between stage I and II disease. Multivariate logical regression showed that only the degree of enhancement was an independent predictor of the thymoma stage. The area under the receiver operating characteristic curve (AUC) of routine CT images for classifying thymoma as MK stage I or II was low (AUC =0.639). The AUC of the 3D-DenseNet model showed better performance with a higher AUC (0.773). ROIs outlined by segmentation labels performed better (AUC =0.773) than those outlined by bounding box labels (AUC =0.722). CONCLUSIONS: Our DL 3D-DenseNet may aid thymoma stage classification, which may ultimately guide surgical treatment and improve outcomes. Compared with conventional methods, this approach provides improved staging accuracy. Moreover, ROIs labeled by segmentation is more recommendable when the sample size is limited.

microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma.

Mesenchymal stem cells (MSCs) have been demonstrated to have promising therapeutic benefits for a variety of neurological diseases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell (RGC) survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1ß, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microglial activation, partly via the action of stanniocalcin 1 (STC1). Furthermore, we found that microRNA-21a-5p (miR-21) and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR-21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.

Highly Dispersed Nickel-Containing Mesoporous Silica with Superior Stability in Carbon Dioxide Reforming of Methane: The Effect of Anchoring.

A series of nickel-containing mesoporous silica samples (Ni-SiO2) with different nickel content (3.1%-13.2%) were synthesized by the evaporation-induced self-assembly method. Their catalytic activity was tested in carbon dioxide reforming of methane. The characterization results revealed that the catalysts, e.g., 6.7%Ni-SiO2, with highly dispersed small nickel particles, exhibited excellent catalytic activity and long-term stability. The metallic nickel particle size was significantly affected by the metal anchoring effect between metallic nickel particles and unreduced nickel ions in the silica matrix. A strong anchoring effect was suggested to account for the remaining of small Ni particle size and the improved catalytic performance.

Dual function of RGD-modified VEGI-192 for breast cancer treatment.

Identification of endogenous angiogenesis inhibitors has led to development of an increasingly attractive strategy for cancer therapy and other angiogenesis-driven diseases. Vascular endothelial growth inhibitor (VEGI), a potent and relatively nontoxic endogenous angiogenesis inhibitor, has been intensively studied, and this work shed new light on developing promising anti-angiogenic strategies. It is well-documented that the RGD (Arg-Gly-Asp) motif exhibits high binding affinity to integrin α(v)ß(3), which is abundantly expressed in cancer cells and specifically associated with angiogenesis on tumors. Here, we designed a fusion protein containing the special RGD-4C motif sequence and VEGI-192, aimed at offering more effective multiple targeting to tumor cells and tumor vasculature, and higher anti-angiogenic and antitumor efficacy. Functional tests demonstrated that the purified recombinant human RGD-VEGI-192 protein (rhRGD-VEGI-192) potently inhibited endothelial growth in vitro and suppressed neovascularization in chicken chorioallantoic membrane in vivo, to a higher degree as compared with rhVEGI-192 protein. More importantly, rhRGD-VEGI-192, but not rhVEGI-192 protein, could potentially target MDA-MB-435 breast tumor cells, significantly inhibiting growth of MDA-MB-435 cells in vitro, triggered apoptosis in MDA-MB-435 cells by activation of caspase-8 as well as caspase-3, which was mediated by activating the JNK signaling associated with upregulation of pro-apoptotic protein Puma, and consequently led to the observed significant antitumor effect in vivo against a human breast cancer xenograft. Our study indicated that the RGD-VEGI-192 fusion protein might represent a novel anti-angiogenic and antitumor strategy.