Downgrading Breast Imaging Reporting and Data System categories in ultrasound using strain elastography and computer-aided diagnosis system: a multicenter, prospective study.

OBJECTIVE: To determine whether adding elastography strain ratio (SR) and a deep learning based computer-aided diagnosis (CAD) system to breast ultrasound (US) can help reclassify Breast Imaging Reporting and Data System (BI-RADS) 3 and 4a-c categories and avoid unnecessary biopsies. METHODS: This prospective, multicentre study included 1049 masses (691 benign, 358 malignant) with assigned BI-RADS 3 and 4a-c between 2020 and 2022. CAD results was dichotomized possibly malignant vs. benign. All patients underwent SR and CAD examinations and histopathological findings were the standard of reference. Reduction of unnecessary biopsies (biopsies in benign lesions) and missed malignancies after reclassified (new BI-RADS 3) with SR and CAD were the outcome measures. RESULTS: Following the routine conventional breast US assessment, 48.6% (336 of 691 masses) underwent unnecessary biopsies. After reclassifying BI-RADS 4a masses (SR cut-off <2.90, CAD dichotomized possibly benign), 25.62% (177 of 691 masses) underwent an unnecessary biopsies corresponding to a 50.14% (177 vs. 355) reduction of unnecessary biopsies. After reclassification, only 1.72% (9 of 523 masses) malignancies were missed in the new BI-RADS 3 group. CONCLUSION: Adding SR and CAD to clinical practice may show an optimal performance in reclassifying BI-RADS 4a to 3 categories, and 50.14% masses would be benefit by keeping the rate of undetected malignancies with an acceptable value of 1.72%. ADVANCES IN KNOWLEDGE: Leveraging the potential of SR in conjunction with CAD holds immense promise in substantially reducing the biopsy frequency associated with BI-RADS 3 and 4A lesions, thereby conferring substantial advantages upon patients encompassed within this cohort.

The Emergence of the Potential Therapeutic Targets: Ultrasound-Based Radiomics in the Prediction of Human Epidermal Growth Factor Receptor 2-Low Breast Cancer.

RATIONALE AND OBJECTIVES: To evaluate whether ultrasound-based radiomics features can effectively predict HER2-low expression in patients with breast cancer (BC). MATERIAL AND METHODS: Between January 2021 and June 2023, patients who received US scans with pathologically confirmed BC in this multicenter study were included. In total, 383 patients from institution 1 were comprised of training set, 233 patients from institution 2 were comprised of validation set and 149 patients from institution 3 were comprised of external validation set. Radiomics features were derived from conventional ultrasound (US) images. The minimum redundancy and maximum relevancy and the least absolute shrinkage and selector operation algorithm were used to generate an US-based radiomics score (RS). Multivariable logistic regression analysis was used to select variables associated with HER2 expressions. The diagnostic performance of the RS was evaluated through the area under the receiver operating characteristic curve (AUC). RESULTS: In the training set, the RS yield an AUC of 0.81 (95%CI: 0.76-0.84) for differentiation HER2-zero from HER2-low and -positive cases, and performed well in validation set (AUC 0.84, 95%CI: 0.78-0.88) and external validation set (AUC 0.82, 95%CI: 0.73-0.90). In the subgroups analysis, the RS showed good performance in distinguishing HER2-zero from HER2 1 + , HER2 2 + and HER2-low tumors (AUC range, 0.79-0.87). CONCLUSION: The RS based on conventional US is proven effective for predicting HER2-low expression in BC.

Combining Potential Strain Elastography and Radiomics for Diagnosing Breast Lesions in BI-RADS 4: Construction and Validation a Predictive Nomogram.

RATIONALE AND OBJECTIVES: To develop a nomogram by integrating B-mode ultrasound (US), strain ratio (SR), and radiomics signature (RS) effectively differentiating between benign and malignant lesions in the Breast Imaging Reporting and Data System (BI-RADS) 4. MATERIALS AND METHODS: We retrospectively recruited 709 consecutive patients who were assigned a BI-RADS 4 and underwent curative resection or biopsy between 2017 and 2022. US images were collected before surgery. A RS was developed through a multistep feature selection and construction process. Histology findings served as the gold standard. Univariate and multivariate regression analysis were employed to analyze the clinical and US characteristics and identify variables for developing a nomogram. The calibration and discrimination of the nomogram were conducted to evaluate its performance. RESULTS: The study included a total of 709 patients, with 497 in the training set and 212 in the validation set. In the training set, the B-mode US had an AUC of 0.84 (95% confidence interval [CI], 0.80, 0.87). The SR demonstrated an AUC of 0.78 (95% CI, 0.74, 0.82), while the RS showed an AUC of 0.85 (95% CI, 0.81, 0.88). Notably, the nomogram exhibited superior performance compared to the conventional US, SR, and RS (AUC=0.93, both p < 0.05, as per the Delong test). The clinical usefulness of the nomogram was favorable. CONCLUSION: The calibrated nomogram can be specifically designed to predict the malignancy of breast lesions in the BI-RADS 4 category.

Autophagy-dependent Na+-K+-ATPase signalling and abnormal urate reabsorption in hyperuricaemia-induced renal tubular injury.

Increasing evidence indicates that hyperuricaemia (HUA) is not only a result of decreased renal urate excretion but also a contributor to kidney disease. Na+-K+-ATPase (NKA), which establishes the sodium gradient for urate transport in proximal tubular epithelial cells (PTECs), its impairment leads to HUA-induced nephropathy. However, the specific mechanism underlying NKA impairment-mediated renal tubular injury and increased urate reabsorption in HUA is not well understood. In this study, we investigated whether autophagy plays a key role in the NKA impairment signalling and increased urate reabsorption in HUA-induced renal tubular injury. Protein spectrum analysis of exosomes from the urine of HUA patients revealed the activation of lysosomal processes, and exosomal expression of lysosomal-associated membrane protein-2 was associated with increased serum levels and decreased renal urate excretion in patients. We demonstrated that high uric acid (UA) induced lysosome dysfunction, autophagy and inflammation in a time- and dose-dependent manner and that high UA and/or NKA α1 siRNA significantly increased mitochondrial abnormalities, such as reductions in mitochondrial respiratory complexes and cellular ATP levels, accompanied by increased apoptosis in cultured PTECs. The autophagy inhibitor hydroxychloroquine (HCQ) ameliorated NKA impairment-mediated mitochondrial dysfunction, Nod-like receptor pyrin domain-containing protein 3 (NLRP3)-interleukin-1ß (IL-1ß) production, and abnormal urate reabsorption in PTECs stimulated with high UA and in rats with oxonic acid (OA)-induced HUA. Our findings suggest that autophagy plays a pivotal role in NKA impairment-mediated signalling and abnormal urate reabsorption in HUA-induced renal tubular injury and that inhibition of autophagy by HCQ could be a promising treatment for HUA.

Effects of Two Botulinum Toxin Type a Evaluated by Shear Wave Elastography and Electromyographic Measurements of Masseter Reduction.

ABSTRACT: The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxin A and Chinese botulinum toxin type A (CBA) for masseter reduction using elastography and electromyographic measurement. Female subjects aged 21 to 38 years with benign masseter hypertrophy received 1 treatment of either 50 units onabotulinumtoxin A or 50 units CBA in a double-blind clinical trial. The study enrolled 102 subjects (204 sides of masseters); 51 subjects per group. The thickness and stiffness of the masseter muscle and the electromyographic changes were evaluated before and 1, 4, 12, and 24 weeks after injection. One week after injection, the thickness of the masseter muscle did not change significantly, but the stiffness was reduced by 5% to 9%. After 4 weeks of injection, masseter muscle thickness, stiffness and strength decreased significantly compared with before injection. The changes were significantly at 12 weeks. Muscle stiffness measured by Shear-wave elastography was significantly reduced by 20% to 32% in the relaxed state and 25% to 47% in the contractile state. The electromyography showed that masseter muscle strength changed consistently with Shear-wave elastography value before and after injection. Six months after injection, ultrasound and electromyography showed that the masseter muscle thickness and stiffness began to recover. Between the 2 groups, there are no significant difference in thickness, stiffness and muscle strength reduction of masseters after treatment ( P > 0.05), as well as in side effects ( P > 0.05). Onabotulinumtoxin A and CBA were comparable in the efficacy and safety for masseter reduction.

Superb microvascular imaging is as sensitive as contrast-enhanced ultrasound for detecting synovial vascularity in rheumatoid arthritis.

Background: Detection of synovitis is essential for assessing rheumatoid arthritis (RA) activity and predicting prognosis. This study aimed to compare the diagnostic performance of superb microvascular imaging (SMI) with that of contrast-enhanced ultrasound (CEUS) in patients with RA in clinical remission. Methods: SMI and CEUS were applied to 63 patients with active RA and 48 patients with RA in clinical remission. Differences in positive synovial vascularity (SV) and its semi-quantitative scale were observed, and the correlations of SMI and CEUS results with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were analyzed. Results: For the 63 joints with active RA, the detection rates of SV as determined by SMI and CEUS were 90.5% (95% CI: 83.0-97.9%) and 93.7% (95% CI: 87.5-99.8%), respectively, with no significant difference observed between the two modalities (t=-1.137; P=0.260). There was good agreement between the two modalities in detecting positive blood flow (Kappa =0.784) and blood flow signal score (Kappa =0.792). For the 48 joints with clinical remission, the detection rates of SV determined by SMI and CEUS were 79.2% (95% CI: 67.2-91.1%) and 83.3% (95% CI: 72.4-94.3%), respectively, with no significant difference found between the two modalities (t=1.000; P=0.322). There was high consistency between the two modalities in detecting positive blood flow (Kappa =0.727) and blood flow signal score (Kappa =0.661). The vascularity scores of SMI and CEUS were positively correlated with CRP, ESR, and RF in the joints with active RA, but not in those with clinical remission. Conclusions: SMI is as sensitive as CEUS for detecting vessels in the synovium and displaying local SV in patients with RA who achieve clinical remission.

The quantitative evaluation of contrast-enhanced ultrasound in the differentiation of small renal cell carcinoma subtypes and angiomyolipoma.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been widely used for renal lesion diagnosis and differential diagnosis. However, qualitative analysis of CEUS is subject to examinations with low reproducibility. This study aims to investigate the diagnostic value of CEUS quantitative parameters in differentiating small renal cell carcinoma (RCC) subtypes and angiomyolipoma (AML). METHODS: A retrospective analysis was performed on 97 cases of a small renal mass undergoing a CEUS before a radical or partial nephrectomy procedure. A region of interest (ROI) was placed in the tumor's maximum enhanced region (ROImax) as much as possible, and adjacent renal cortex (ROIrefer) was selected from normal renal tissue around a mass of the same depth. The time-intensity curve (TIC) was used to analyze the ROImax and the ROIrefer of the tumors quantitatively. Then the parameters of the ROImax and the ROIrefer, including the differences between the parameters of the ROImax and the ROIrefer, were analyzed statistically. RESULTS: In RCC and clear cell renal cell carcinoma (ccRCC), the peak intensity (PI), slope (SL), area under the curve (AUC), area under the wash-in curve (AWI), area under the wash-out curve (AWO), time to peak intensity (TTP) and the mean transit time (MTT) were statistically significant between ROImax and ROIrefer (all P=0.000). The △PI (△PI = PImax - PIrefer), △SL (△SL = SLmax - SLrefer), △AUC (△AUC = AUCmax - AUCrefer), △AWI (△AWI = AWImax - AWIrefer) and △AWO (△AWO = AWOmax - AWOrefer) of RCC were significantly higher than in AML (P=0.007, 0.000, 0.003, 0.048, 0.009, respectively), while the TTP (△TTP = TTPmax - TTPrefer) and △MTT (△MTT = MTTmax - MTTrefer) of RCC were significantly lower (both P=0.000). In comparison with papillary renal cell carcinoma (pRCC) and chromophobe renal cell carcinoma (chRCC), the △PI, △SL, △AUC and △AWO of ccRCC were all larger (all P<0.05). The sensitivity, specificity, and AUC of the combination of parameter difference for differentiating RCC from AML were 100%, 81.2%, and 0.965, respectively, and for differentiating ccRCC from pRCC and chRCC, 85.71%, 85.92% and 0.911, respectively. CONCLUSIONS: CEUS quantitative parameters have value in differentiating small RCC from AML and distinguishing ccRCC from pRCC and chRCC.

The Value of Contrast-Enhanced Ultrasound in Diagnosing Small Renal Cell Carcinoma Subtypes and Angiomyolipoma.

OBJECTIVES: To retrospectively explore the value of contrast-enhanced ultrasound (CEUS) in differentiating small renal cell carcinomas (RCCs) from angiomyolipomas (AMLs), and distinguishing between clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). METHODS: A total of 151 patients with small renal masses (110 ccRCCs, 12 pRCCs, 9 chRCCs, and 20 AMLs) were enrolled between August 2016 and October 2019. RESULTS: There were significant differences in terms of enhancement intensity (EI), enhancement homogeneity, perilesional rim-like enhancement (PRE), wash in, and wash out (WO) between RCC and AML (P = .000, .011, .000, .001, .000, respectively). Although there was no significant difference in EI between pRCC and chRCC (P = .272), EI of ccRCC was higher than that of pRCC (P = .000) and chRCC (P = .010). Multivariate regression analysis showed PRE and fast WO were related to RCC (OR = 18.189, 15.141, respectively). Although there were no significant differences in the sensitivity and area under the curve (AUC) between PRE and fast WO (95.0% vs. 95.0%, P = 1.000 and .880 vs. 0.799, P = .123, respectively), the specificity of PRE in predicting RCC was higher than that of fast WO (80.92% vs. 64.89%, P = .011). The sensitivity, specificity, and AUC of the two characteristics combination for differentiating RCC from AML were 95.0%, 90.8%, and 0.920, respectively, and that of EI for differentiating between ccRCC, pRCC, and chRCC were 81.0%, 78.2%, and 0.796, respectively. CONCLUSIONS: CEUS has value in differentiating small RCCs from AMLs and distinguishing ccRCC, a subtype associated with a greater likelihood of malignant behavior from pRCC and chRCC.

Role of Superb Microvascular Imaging in Differentiating Between Malignant and Benign Solid Breast Masses.

INTRODUCTION: The purpose of this study was to evaluate the diagnostic performance of superb microvascular imaging (SMI) in breast lesions. MATERIALS AND METHODS: Eighty-five solid breast lesions were studied with color Doppler flow imaging (CDFI), power Doppler imaging (PDI), monochromatic SMI (mSMI), and contrast-enhanced ultrasonography (CEUS). The penetrating vessels (PVs) and microvascular morphologic and distribution features of the breast tumors were evaluated for each modality. RESULTS: The diagnostic accuracies of CDFI, PDI, mSMI, and CEUS were calculated and compared. Surgical pathologic analysis showed 47 benign and 38 malignant lesions. Compared with CDFI and PDI, mSMI and CEUS detected more PVs in breast lesions. The microvascular architecture showed significant differences between benign and malignant lesions. Benign lesions mainly displayed avascular, line-like, and branch-like patterns, and malignant lesions tended to display root hair-like and crab claw-like patterns. mSMI and CEUS identified more root hair-like and crab claw-like patterns in malignant lesions than CDFI and PDI. The sensitivity, negative predictive value, and accuracy of mSMI findings in diagnosing malignancy based on PVs and vascular patterns were both higher than those of CDFI and PDI. CONCLUSIONS: mSMI is equal to CEUS and superior to CDFI and PDI in identifying microvascular and discriminating malignant and benign breast masses.

The independent indicators for differentiating renal cell carcinoma from renal angiomyolipoma by contrast-enhanced ultrasound.

BACKGROUND: The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC. METHODS: A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed. RESULTS: There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML (P < 0.05 for all). Multivariate analysis indicated that perilesional rim-like enhancement (P = 0.035, odds ratio [OR] = 9.907, 95% confidence interval [CI]: 1.169-83.971) and fast wash out (P = 0.001, OR = 9.755, 95%[CI]: 2.497-38.115) were independent indicators for predicting RCC. The area under the receiver operating characteristic (ROC) curve (AUC) for perilesional rim-like enhancement was 0.838 (95% CI: 0.774-0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI:0.768-0.885) with 74.7% sensitivity and 81.8% specificity. CONCLUSIONS: This study indicated that CEUS has value in differentiating RCC and AML. Present perilesional rim-like enhancement and fast wash out may be important indicators for predicting RCC.