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.

Identification of CaPs locus involving in purple stripe formation on unripe fruit, reveals allelic variation and alternative splicing of R2R3-MYB transcription factor in pepper (Capsicum annuum L.).

The purple color of unripe pepper fruit is attributed to the accumulation of anthocyanins. Only a few genes controlling the biosynthesis and regulation of anthocyanins have been cloned in Capsicum. In this study, we performed a bulked segregant analysis of the purple striped trait using an F2 population derived from a cross between the immature purple striped fruit line Chen12-4-1-1-1-1 and the normal green fruit line Zhongxian101-M-F9. We mapped the CaPs locus to an 841.39 kb region between markers M-CA690-Xba and MCA710-03 on chromosome 10. CA10g11690 encodes an R2R3-MYB transcription factor that is involved in the biosynthesis of anthocyanins as the best candidate gene. Overexpression and silencing in transformed tobacco (Nicotiana tabacum) lines indicated that CA10g11690 is involved in the formation of purple stripes in the exocarp. A comparison of parental sequences identified an insertion fragment of 1,926 bp in the second intron region of Chen12-4, and eight SNPs were detected between the two parents. Additionally, there were 49 single nucleotide polymorphic variations, two sequence deletions, and four sequence insertions in the promoter region. We found that CA10g11690 undergoes alternative splicing and generates different transcripts. Thus, the functional transcript of CA10g11690 appeared to be primarily involved in the development of purple phenotype in the exocarp. Our data provide new insight into the mechanism of anthocyanin biosynthesis and a theoretical basis for the future breeding of purple striped pepper varieties.

Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm.

Background: Some women die despite the favorable prognosis of small breast cancers. Breast ultrasound features may reflect pathological and biological characteristics of a breast tumor. This study aimed to explore whether ultrasound features could identify small breast cancers with poor outcomes. Methods: This retrospective study examined confirmed breast cancers with a size of <20 mm diagnosed in our hospital between 02/2008 and 08/2019. Clinicopathological and ultrasound features were compared between alive and deceased breast cancer patients. Survival was analyzed using the Kaplan-Meier curves. Multivariable Cox proportional hazards models were used to examine the factors associated with breast cancer-specific survival (BCSS) and disease-free survival (DFS). Results: Among the 790 patients, the median follow-up was 3.5 years. The deceased group showed higher frequencies of spiculated (36.7% vs. 11.2%, P<0.001), anti-parallel orientation (43.3% vs. 15.4%, P<0.001), and spiculated morphology combined with anti-parallel orientation (30.0% vs. 2.4%, P<0.001). Among 27 patients with spiculated morphology and anti-parallel orientation, nine cancer-specific deaths and 11 recurrences occurred, for a 5-year BCSS of 77.8% and DFS of 66.7%, while 21 breast-cancer deaths and 41 recurrences occurred among the remaining patients with higher 5-year BCSS (97.8%, P<0.001) and DFS (95.4%, P<0.001). Spiculated and anti-parallel orientation (HR=7.45, 95%CI: 3.26-17.00; HR=6.42, 95%CI: 3.19-12.93), age ≥55 years (HR=5.94, 95%CI: 2.24-15.72; HR=1.98, 95%CI: 1.11-3.54), and lymph nodes metastasis (HR=3.99, 95%CI: 1.89-8.43; HR=2.99, 95%CI: 1.71-5.23) were independently associated with poor BCSS and DFS. Conclusions: Spiculated and anti-parallel orientation at ultrasound are associated with poor BCSS and DFS in patients with primary breast cancer <20 mm.

Silencing of Pepper CaFtsH1 or CaFtsH8 Genes Alters Normal Leaf Development.

Filamentation temperature-sensitive H (FtsH) is a proteolytic enzyme that plays an important role in plant photomorphogenesis and stress resistance. However, information regarding the FtsH family genes in pepper is limited. In our research, through genome-wide identification, 18 members of the pepper FtsH family (including five FtsHi members) were identified and renamed based on phylogenetic analysis. CaFtsH1 and CaFtsH8 were found to be essential for pepper chloroplast development and photosynthesis because FtsH5 and FtsH2 were lost in Solanaceae diploids. We found that the CaFtsH1 and CaFtsH8 proteins were located in the chloroplasts and specifically expressed in pepper green tissues. Meanwhile, CaFtsH1 and CaFtsH8-silenced plants created by virus-induced gene silencing exhibited albino leaf phenotypes. In addition, CaFtsH1-silenced plants were observed to contain very few dysplastic chloroplasts and lost the capacity for photoautotrophic growth. Transcriptome analysis revealed that the expression of chloroplast-related genes such as those coding the photosynthesis-antenna protein and structural proteins was downregulated in CaFtsH1-silenced plants, resulting in the inability to form normal chloroplasts. This study improves our understanding of pepper chloroplast formation and photosynthesis through the identification and functional study of CaFtsH genes.

Deep learning radiomics of ultrasonography for differentiating sclerosing adenosis from breast cancer.

OBJECTIVES: The purpose of our study is to present a method combining radiomics with deep learning and clinical data for improved differential diagnosis of sclerosing adenosis (SA)and breast cancer (BC). METHODS: A total of 97 patients with SA and 100 patients with BC were included in this study. The best model for classification was selected from among four different convolutional neural network (CNN) models, including Vgg16, Resnet18, Resnet50, and Desenet121. The intra-/inter-class correlation coefficient and least absolute shrinkage and selection operator method were used for radiomics feature selection. The clinical features selected were patient age and nodule size. The overall accuracy, sensitivity, specificity, Youden index, positive predictive value, negative predictive value, and area under curve (AUC) value were calculated for comparison of diagnostic efficacy. RESULTS: All the CNN models combined with radiomics and clinical data were significantly superior to CNN models only. The Desenet121+radiomics+clinical data model showed the best classification performance with an accuracy of 86.80%, sensitivity of 87.60%, specificity of 86.20% and AUC of 0.915, which was better than that of the CNN model only, which had an accuracy of 85.23%, sensitivity of 85.48%, specificity of 85.02%, and AUC of 0.870. In comparison, the diagnostic accuracy, sensitivity, specificity, and AUC value for breast radiologists were 72.08%, 100%, 43.30%, and 0.716, respectively. CONCLUSIONS: A combination of the CNN-radiomics model and clinical data could be a helpful auxiliary diagnostic tool for distinguishing between SA and BC.

Carotid plaque score and ischemic stroke risk stratification through a combination of B-mode and contrast-enhanced ultrasound in patients with low and intermediate carotid stenosis.

Objective: The occurrence of ischemic stroke (IS) is closely related to the characteristics of carotid plaque (CP). Due to the effect of stroke risk stratification based on B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) that has not been studied in patients with low and intermediate carotid stenosis, we construct and validate a CP score and ischemic stroke risk stratification (ISRS) using a combination of B-mode and CEUS, in order to provide new convenient strategies to stratify these patients to prevent stroke. Materials and methods: This retrospective study evaluated 705 patients with low and intermediate carotid stenosis who underwent B-mode and CEUS from November 2021 to April 2023. Qualitative B-mode and CEUS features of carotid plaques were analyzed using a univariable and multivariable logistic regression to construct the CP score. Then, we combined the CP score with Essen stroke risk score (ESRS) to develop ISRS. Results: This study included a total of 705 patients with low and intermediate carotid stenosis, of which 394 were symptomatic patients (with a mean age of 71.03 ± 10.48 years) and 311 were asymptomatic patients (with a mean age of 65.13 ± 10.31 years). Plaque echogenicity, plaque morphology, carotid intima-media thickness in B-mode US and intraplaque neovascularization grading and perfusion pattern in CEUS were significantly associated with IS. The ISRS incorporating these five predictors and ESRS showed good discrimination and calibration in both primary cohort [area under the curve (AUC), 0.91; Hosmer-Lemeshow test, p = 0.903] and validation cohort (AUC, 0.84; Hosmer-Lemeshow test, p = 0.886). Conclusion: We developed an effective and practical tool to identify and stratify patients with low and intermediate carotid stenosis, based on the CP score and ISRS estimation. Our study may provide new insights into managing patients with no indication of surgery.

Multi-parameter ultrasonography-based predictive model for breast cancer diagnosis.

Objectives: To develop, validate, and evaluate a predictive model for breast cancer diagnosis using conventional ultrasonography (US), shear wave elastography (SWE), and contrast-enhanced US (CEUS). Materials and methods: This retrospective study included 674 patients with 674 breast lesions. The data, a main and an independent datasets, were divided into three cohorts. Cohort 1 (80% of the main dataset; n = 448) was analyzed by logistic regression analysis to identify risk factors and establish the predictive model. The area under the receiver operating characteristic curve (AUC) was analyzed in Cohort 2 (20% of the main dataset; n = 119) to validate and in Cohort 3 (the independent dataset; n = 107) to evaluate the predictive model. Results: Multivariable regression analysis revealed nine independent breast cancer risk factors, including age > 40 years; ill-defined margin, heterogeneity, rich blood flow, and abnormal axillary lymph nodes on US; enhanced area enlargement, contrast agent retention, and irregular shape on CEUS; mean SWE higher than the cutoff value (P < 0.05 for all). The diagnostic performance of the model was good, with AUC values of 0.847, 0.857, and 0.774 for Cohorts 1, 2, and 3, respectively. The model increased the diagnostic specificity (from 31% to 81.3% and 7.3% to 73.1% in cohorts 2 and 3, respectively) without a significant loss in sensitivity (from 100.0% to 90.1% and 100.0% to 81.8% in cohorts 2 and 3, respectively). Conclusion: The multi-parameter US-based model showed good performance in breast cancer diagnosis, improving specificity without a significant loss in sensitivity. Using the model could reduce unnecessary biopsies and guide clinical diagnosis and treatment.

A Convolutional Neural Network Based on Ultrasound Images of Primary Breast Masses: Prediction of Lymph-Node Metastasis in Collaboration With Classification of Benign and Malignant Tumors.

Purpose: A convolutional neural network (CNN) can perform well in either of two independent tasks [classification and axillary lymph-node metastasis (ALNM) prediction] based on breast ultrasound (US) images. This study is aimed to investigate the feasibility of performing the two tasks simultaneously. Methods: We developed a multi-task CNN model based on a self-built dataset containing 5911 breast US images from 2131 patients. A hierarchical loss (HL) function was designed to relate the two tasks. Sensitivity, specificity, accuracy, precision, F1-score, and analyses of receiver operating characteristic (ROC) curves and heatmaps were calculated. A radiomics model was built by the PyRadiomics package. Results: The sensitivity, specificity and area under the ROC curve (AUC) of our CNN model for classification and ALNM tasks were 83.5%, 71.6%, 0.878 and 76.9%, 78.3%, 0.836, respectively. The inconsistency error of ALNM prediction corrected by HL function decreased from 7.5% to 4.2%. Predictive ability of the CNN model for ALNM burden (≥3 or ≥4) was 77.3%, 62.7%, and 0.752, and 66.6%, 76.8%, and 0.768, respectively, for sensitivity, specificity and AUC. Conclusion: The proposed multi-task CNN model highlights its novelty in simultaneously distinguishing breast lesions and indicating nodal burden through US, which is valuable for "personalized" treatment.

Ultrasonic multimodality imaging features and the classification value of nonpuerperal mastitis.

OBJECTIVE: To explore the value of ultrasonic multimodality imaging for characterizing nonpuerperal mastitis (NPM) lesions and feasibility of distinguishing different subtypes. METHODS: Thirty-eight NPM lesions were assessed using conventional ultrasonography (US), strain elastography (SE), and contrast-enhanced ultrasound (CEUS). The lesions were confirmed pathologically and classified as granulomatous lobular mastitis (GLM), plasma cell mastitis (PCM), or nonspecific mastitis (NSM). Furthermore, diagnostic indicators were evaluated. The diagnostic performances of the modalities were compared using the area under the receiver operating characteristic curve (AUC). RESULTS: The overall morphological features on US differed significantly between the GLM and PCM groups (p = 0.002). Lesion size (≤10 mm) (p = 0.003) and mean SE score (p = 0.001) differed significantly between the PCM and NSM groups. The frequent NPM characteristic on CEUS was hyperenhancement with (or without) increased lesion size; intergroup differences were not significant. Breast Imaging Reporting and Data System > 3 was considered to indicate malignancy; accordingly, the accuracy of US alone, US with CEUS, and US with SE was 10.5%, 21.1%, and 65.8%, respectively. Moreover, the AUC for US with SE for classifying GLM and PCM was 0.616. CONCLUSION: CEUS cannot accurately classify NPM subtypes, while US and SE are valuable for classification.

The association between conventional ultrasound and contrast-enhanced ultrasound appearances and pathological features in small breast cancer.

OBJECTIVE: To investigate the association between ultrasound appearances and pathological features in small breast cancer. MATERIALS AND METHODS: A total of 186 small breast cancers in 186 patients were analyzed in this retrospective study from January 2015 to December 2019 according to pathological results. Forty-seven cases of axillary lymph node metastasis were found. All patients underwent radical axillary surgery following conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. The association between ultrasound appearances and pathological features was analyzed using univariate distributions and multivariate analysis. Then, a logistic regression model was established using the pathological diagnosis of lymph node metastasis and biochemical indicators as the dependent variable and the ultrasound appearances as independent variables. RESULTS: In small breast cancer, risk factors of axillary lymph node metastasis were crab claw-like enhancement on CEUS and abnormal axillary lymph nodes on US. The logistic regression model was established as follows: (axillary lymph node metastasis) = 1.100×(crab claw-like enhancement of CEUS) + 2.749×(abnormal axillary lymph nodes of US) -5.790. In addition, irregular shape on CEUS and posterior echo attenuation on US were risk factors for both positive estrogen receptor and progesterone receptor expression, whereas calcification on US was a risk factor for positive Her-2 expression. A specific relationship could be found using the following logistic models: (positive ER expression) = 1.367×(irregular shape of CEUS) + 1.441×(posterior echo attenuation of US) -5.668; (positive PR expression) = 1.265×(irregular shape of CEUS) + 1.136×(posterior echo attenuation of US) -4.320; (positive Her-2 expression) = 1.658×(calcification of US) -0.896. CONCLUSION: Logistic models were established to provide significant value for the prediction of pre-operative lymph node metastasis and positive biochemical indicators, which may guide clinical treatment.

Conventional and contrast-enhanced ultrasound features in sclerosing adenosis and correlation with pathology.

OBJECTIVES: To evaluate the efficacy of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in differential diagnosis of sclerosing adenosis (SA) from malignance and investigate the correlated features with pathology. METHODS: We retrospectively enrolled 103 pathologically confirmed SA. All lesions were evaluated with conventional US while 31 lesions with CEUS. Lesions were divided into SA with or without benign lesions (Group 1, n = 81) and SA with malignancy (Group 2, n = 22). Performance of two methods were analyzed. The ultrasonographic characteristics were compared between two groups with Student's t-test for measurement and chi-squared or Fisher's exact test for count data. RESULTS: There were 22 lesions complicated with malignancy, and the mean age of Group 2 was higher than Group 1 (55.27 vs. 41.57, p < 0.001). The sensitivity, specificity and accuracy of conventional US and CEUS were 95.45%, 46.91%, 57.28% and 100%, 62.5%, 70.97%. Angularity (p < 0.001), spicules (p = 0.023), calcification (p = 0.026) and enlarged scope (p = 0.012) or crab claw-like enhancement (p = 0.008) in CEUS were more frequent detected in SA with malignancy. CONCLUSIONS: Though CEUS showed an improved accuracy, the performance of ultrasound in the diagnosis of SA was limited. Awareness and careful review of the histopathologically related imaging features can be helpful in the diagnosis of SA.

Engineering of SPECT/Photoacoustic Imaging/Antioxidative Stress Triple-Function Nanoprobe for Advanced Mesenchymal Stem Cell Therapy of Cerebral Ischemia.

The precise transplantation, long-term tracking, and maintenance of stem cells with maximizing therapeutic effect are significant challenges in stem cell-based therapy for stroke treatment. In this study, a unique core-shell labeling nanoagent was prepared by encapsulating a cobalt protoporphyrin IX (CoPP)-loaded mesoporous silica nanoparticle (CPMSN) into a 125I-conjugated/spermine-modified dextran polymer (125I-SD) by microfluidics for mesenchymal stem cell (MSC) tracking and activity maintenance. The CPMSN core not only exhibits excellent photoacoustic (PA) imaging performance induced by the intermolecular aggregation of CoPP within the mesopores but also protects the MSCs against oxidative stress by sustained release of CoPP. Meanwhile, the addition of a 125I-SD shell can increase the uptake efficiency in MSCs without inducing cell variability and enable the single-photon-emission computed tomography (SPECT) nuclear imaging. In vivo results indicated that CPMSN@125I-SD labeling could allow for an optimal combination of instant imaging of MSCs, with PA to guide intracerebral injection, followed by multiple time point SPECT imaging to consecutively track the cell homing. Importantly, the sustained release of CoPP from CPMSN@125I-SD significantly increased the survival of MSCs after injection into an ischemic mouse brain and promoted neurobehavioral recovery in ischemic mice. Thus, CPMSN@125I-SD represents a robust theranostic probe for both MSC tracking and maintaining their therapeutic effect in the treatment of brain ischemia.

Qualitative analysis of contrast-enhanced ultrasound in the diagnosis of small, TR3-5 benign and malignant thyroid nodules measuring ≤1 cm.

OBJECTIVE: To evaluate the performance of contrast-enhanced ultrasound in the diagnosis of small, solid, TR3-5 benign and malignant thyroid nodules (≤1 cm). METHODS: From January 2016 to March 2018, 185 thyroid nodules from 154 patients who underwent contrast enhanced ultrasound (CEUS) and fine-needle aspiration or thyroidectomy in Shanghai General Hospital were included. The χ2 test was used to compare the CEUS characteristics of benign and malignant thyroid nodules, and the CEUS features of malignant nodules assigned scores. The total score of the CEUS features and the scores of the above nodules were evaluated according to the latest 2017 version of the Thyroid Imaging Reporting and Data System (TI-RADS). The diagnostic performance of the two were compared based on the receiver operating characteristic curves generated for benign and malignant thyroid nodules. RESULTS: The degree, enhancement patterns, boundary, shape, and homogeneity of enhancement in thyroid small solid nodules were significantly different (p＜0.05). No significant differences were seen between benign and malignant thyroid nodules regarding completeness of enhancement and size of enhanced lesions (p＞0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the TI-RADS classification TR5 in diagnosis of malignant nodules were 90.10%, 55.95%, 74.59%, 72.22%, and 82.46%, respectively (area under the curve [AUC]=0.738; 95% confidence interval[CI], 0.663-0.813). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the total score of CEUS qualitative analysis indicators were 86.13%, 89.29%, 87.57%, 90.63%, and 84.27% respectively (AUC = 0.916; 95% CI, 0.871-0.961). CONCLUSION: CEUS qualitative analysis is superior to TI-RADS in evaluating the diagnostic performance of small, solid thyroid nodules. Qualitative analysis of CEUS has a significantly higher specificity for diagnosis of malignant thyroid nodules than TI-RADS. ADVANCES IN KNOWLEDGE: The 2017 version of TI-RADS has recently suggested the malignant stratification of thyroid nodules by ultrasound. In this paper we applied this system and CEUS to evaluate 185 nodules and compare the results with pathological findings to access the diagnostic performance.

Diagnostic efficacy of contrast-enhanced ultrasound for breast lesions of different sizes: a comparative study with magnetic resonance imaging.

OBJECTIVE: This study aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), MRI, and the combined use of the two modalities for differentiating breast lesions of different sizes. METHODS: A total of 406 patients with 406 solid breast masses detected by conventional ultrasound underwent both CEUS and MRI scans. Histological results were used as reference standards. The lesions were categorized into three groups according to size (Group 1, ≤ 20 mm; Group 2, > 20 mm, Group 3: total lesions). Sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curve analysis were used to assess the diagnostic performance of these imaging methods for breast lesions. RESULTS: There were 194 benign and 212 malignant breast lesions according to the histological diagnosis. Compared with MRI, CEUS demonstrated similar sensitivity in detecting breast cancer (p = 1.0000 for all) in all the three groups. With regard to specificity, accuracy, and the area under the ROC curve (Az) values, MRI showed a better performance than that shown by CEUS (p ＜0.05 for all), and the combination of the two modalities improved the diagnostic performance of CEUS alone significantly (p ＜0.05 for all) in all the three groups. However, the diagnostic specificity and accuracy of the combined method was not superior to that of MRI alone except for Group 2. CONCLUSION: CEUS demonstrated good sensitivity in detecting breast cancer, and the combined use with MRI can optimize the diagnostic specificity and accuracy in breast cancer prediction. ADVANCES IN KNOWLEDGE: Few studies have compared the diagnostic efficacy of CEUS and MRI, and this study is the first attempt to seek out the diagnostic values for breast lesions of variable sizes (lesions with ≤20 mm and >20 mm).

Value of conventional ultrasound, ultrasound elasticity imaging, and acoustic radiation force impulse elastography for prediction of malignancy in breast lesions.

OBJECTIVE: To evaluate the efficacies of conventional ultrasound (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) elastography in breast malignancy diagnosis. METHODS: We included 315 women (mean age, 44 years; range, 18-81 years) with 336 pathologically proven breast lesions in this retrospective study. All lesions underwent conventional US, EI, and ARFI (including virtual touch tissue imaging [VTI], virtual touch tissue quantification [VTQ], and virtual touch tissue imaging and quantification [VTIQ]) elastography. Multivariate logistic regression analysis was performed to assess 12 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: Irregular lesion shape was the strongest independent predictor for breast malignancy, followed by poorly defined margins, taller than wide dimensions, posterior echo attention, VTIQ, and VTI boundaries (P < 0.05). Area under the ROC curve (AUC) for VTIQ was higher than other significant independent variables. With the best cut-off value of 3.74 m/s, the AUC, sensitivity, and specificity were 0.93 (95% CI: 0.90, 0.96), 90.1%, and 91.1%, respectively. CONCLUSIONS: ARFI elastography is a promising method in breast malignancy prediction, with good diagnostic performance. For patients requiring surgery, the combination of various methods can provide better diagnostic results and may help to reduce unnecessary biopsy or surgery.

Incorporation of contrast-enhanced ultrasound in the differential diagnosis for breast lesions with inconsistent results on mammography and conventional ultrasound.

OBJECTIVE: To identify the efficacy of contrast-enhanced ultrasound (CEUS) in re-evaluating masses with inconsistent Breast Imaging Reporting and Data System (BI-RADS) on mammography (MG) and conventional ultrasound (US). MATERIALS AND METHODS: A total of 637 breast lesions were evaluated with MG, US, and CEUS within 6 months and assessed as BI-RADS MG and US. CEUS was used as an additional screening to rerate BI-RADS US according to a five-point system. Lesions were divided into consistent or inconsistent group on the basis of BI-RADS MG and US assessment. The performance of MG, US, and CEUS in the overall and inconsistent group as well as the clinicopathological differences between consistent and inconsistent group were compared using Z test, Mann-Whitney U test, and t-test. RESULTS: The respective AUCs of MG and US were 0.742, 0.843 for overall group and 0.412, 0.789 for inconsistent group. The corresponding values of rerated CEUS BI-RADS were 0.958 and 0.950, which were significantly prior to those of MG and US (p < 0.001). Younger age, negative lymph node status, and dense breast were significantly associated with inconsistent group. CONCLUSION: Incorporation of CEUS to re-evaluate lesions can improve the diagnostic efficacy comparing to MG or US alone especially when disagreement occurred.

Shear-wave elastography: role in clinically significant prostate cancer with false-negative magnetic resonance imaging.

OBJECTIVES: To analyze the diagnostic value of adding SWE to MRI for the diagnosis of clinically significant prostate cancer with false-negative MRI results. METHODS: This was a retrospective study of 367 patients who underwent MRI, SWE, and prostate biopsy between March 2016 and November 2018 at the Shanghai Tenth People's Hospital. Serum prostate-specific antigen (PSA) and free PSA (fPSA) were measured preoperatively. Diagnostic value and accuracy was determined for MRI alone and MRI + SWE using the receiver operator characteristic curve (ROC) analysis. RESULTS: MRI misdiagnosed 17.9% (21/117) clinically significant prostate cancers, including 15 lesions in the peripheral zone and 6 in the central zone. Both qualitative and quantitative SWE could help detect 66.7% (10/15) significant prostate cancers with false-negative MRI, but there was no association with the Gleason score (p > 0.05). When considering the sextant of the peripheral zone, a significant association was not seen with histopathology in qualitative SWE (p = 0.071) and quantitative SWE (p = 0.598). Among age, PSA, fPSA, volume of the prostate gland, fPSA/PSA, and PSAD, only PSAD (p = 0.019) was associated with SWE results in patients with negative MRI. CONCLUSIONS: Adding SWE to MRI in patients with negative MRI for prostate examination could allow the correct diagnosis of additional patients and reduce the false-negative rate. KEY POINTS: • MRI plays an important role in clinically significant prostate cancers diagnosis. • SWE plays an important role in clinically significant prostate cancers with negative MRI. • Adding SWE to MRI in patients with negative MRI for prostate examination could allow the correct diagnosis of additional patients and reduce the false-negative rate.

Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells.

Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.

Benign lesion evaluation: Factors causing the "stiff rim" sign in breast tissues using shear-wave elastography.

OBJECTIVE:: To investigate the factors causing the "stiff rim" sign in breast lesions using shear-wave elastography. METHODS:: A total of 907 patients with 907 lesions were included retrospectively in this study. Traditional ultrasound and shear-wave elastography imaging were both performed. Patients age, maximum diameter, depth, distance, echogenicity, shape, boundary, margin, internal components, CDFI, calcification, echogenicity attenuation and longitudinal growth of lesions were observed and calculated by both univariate and multivariate analyses. RESULTS:: Univariate analyses indicated that the age, depth, shape, margin, internal components, CDFI, calcification and pathology showed significant difference between the benign lesions with and without a "stiff rim", whereas there was no correlation of "stiff rim" with maximum diameter, distance, boundary, echogenicity, echo attenuation and longitudinal growth of the lesions. Multivariate analysis expressed that CDFI, margin, internal components, depth and age were significantly associated with the "stiff rim" sign in breast benign lesions, whereas there was no correlation with the pathology, shape or calcification of the lesions. CONCLUSIONS:: The "stiff rim" sign can be helpful for differentiation between benign and malignant lesions. Older patients with a "stiff rim" sign whose benign masses are deep, poorly defined, heterogeneous and have a positive CDFI should be examined more closely to avoid unnecessary false-positives. ADVANCES IN KNOWLEDGE:: The "stiff rim" sign can be helpful for differentiation between benign and malignant lesions. Positive CDFI, poorly defined margin, heterogeneous internal components, deep depth and older age were significantly associated with the "stiff rim" sign in benign breast lesions.

Diagnostic value of acoustic radiation force impulse for BI-RADS category 4 breast lesions of different sizes.

OBJECTIVE: To determine the diagnostic value of combined conventional ultrasound (US) and acoustic radiation force impulse (ARFI) imaging for the differential diagnosis of BI-RADS category 4 breast lesions of different sizes. MATERIALS AND METHODS: From April 2013 to January 2015, 283 patients (with a total of 292 breast lesions) who underwent US and ARFI examination were included in this retrospective study. The SWV for the lesion and adjacent normal breast tissue were measured and the SWV ratio was calculated. VTI grade was also assessed. The lesions were separated into three groups on the basis of size, and two combinations of ARFI parameters (SWV + VTI and SWV ratio + VTI) were applied to reassess the BI-RADS categories. Diagnoses were confirmed by pathological examination after biopsy or surgery. ROC analysis was performed to assess the diagnostic efficiency of each method. The Z test was used to compare the difference between AUC of the two methods. RESULTS: Significant improvement was seen in the diagnostic performance of US with the use of the ARFI parameters SWV + VTI (77/179 [43.0%] of BI-RADS category 4A breast lesions were downgraded) and SWV ratio + VTI (64/179 [35.8%] of BI-RADS category 4A breast lesions were downgraded, including two malignant cases that were misdiagnosed as benign) (P < 0.01). The difference between the performances of the two combinations-SWV + VTI and SWV ratio + VTI-was significant only in breast lesions <10 mm in size, where the AUC of SWV ratio + VTI was significantly greater than the AUC of SWV + VTI (0.929 vs. 0.874; P < 0.01). CONCLUSION: Combination of US with ARFI can improve diagnostic performance and help avoid unnecessary biopsy in BI-RADS category 4 breast lesions. The combination of SWV ratio + VTI can improve BI-RADS classification of small lesions (<10 mm size).