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Objective To evaluate high-frequency ultrasound (HFUS) features for diagnosing cutaneous squamous cell carcinoma (cSCC) as a spectrum of progressively advanced malignancies, including precursor actinic keratosis (AK), Bowen's disease (BD), and invasive squamous cell carcinoma (iSCC). Method In this retrospective study, 160 skin lesions diagnosed histopathologically (54 AK, 54 BD, and 52 iSCC) in 160 patients were included. The HFUS features of AK, BD, and iSCC were analyzed. The obtained data were evaluated using univariate and forward multivariate logistic regression analyses. Results The most significant HFUS features in AK were regular surface (odds ratio [OR], 8.42) and irregular basal border (OR, 6.36). The most significant HFUS features in BD were crumpled surface (OR, 19.62) and layer involvement confined to the epidermis (OR, 3.96). The most significant HFUS features in iSCC were concave surface (OR, 27.06), stratum corneum (SC) detachment (OR, 14.41), irregular basal border (OR, 4.01), and convex surface (OR, 3.73). The characteristics of surface features, basal border, and layer involvement could be valuable HFUS clues in the discrimination of AK, BD, and iSCC. Conclusion High-frequency ultrasound is valuable for the differentiation of AK, BD, and iSCC, which may allow dynamic and noninvasive monitoring in the spectrum of cSCC.

The purpose of this study was to develop, validate and test a prediction model for discriminating malignant from benign breast lesions using conventional ultrasound (US), US elastography of strain elastography and contrast-enhanced ultrasound (CEUS). The study included 454 patients with breast imaging-reporting and data system (BI-RADS) category 4 breast lesions identified on histologic examinations. Firstly, 228 breast lesions (cohort 1) were analyzed by logistic regression analysis to identify the risk factors, and a breast malignancy prediction model was created. Secondly, the prediction model was validated in cohort 2 (84 patients) and tested in cohort 3 (142 patients) by using analysis of the area under the receiver operating characteristic curve (AUC). Univariate regression indicated that age ≥40 y, taller than wide shape on US, early hyperenhancement on CEUS and enlargement of enhancement area on CEUS were independent risk factors for breast malignancy (all p0.05). The logistic regression equation was established as follows: p = 1/1+Exp∑[-5.066 + 3.125 x (if age ≥40 y) + 1.943 x (if taller than wide shape) + 1.479 x (if early hyperenhancement) + 4.167 x (if enlargement of enhancement area). The prediction model showed good discrimination performance with an AUC of 0.967 in cohort 1, 0.948 in cohort 2 and 0.920 in cohort 3. By using the prediction model to selectively downgrade category 4a lesions, the re-rated BI-RADS yield an AUC of 0.880 (95% confidence interval [CI], 0.794-0.965) in cohort 2 and 0.870 (95% CI, 0.801-0.939) in cohort 3. The specificity increased from 0.0% (0/35) to 80.0% (28/35) without loss of sensitivity (from 100.0% to 95.9%, p = 0.153) in cohort 2. Similarly, the specificity increased from 0.0% (0/58) to 77.6% (45/58) without loss of sensitivity (from 100.0% to 96.4%, p = 0.081) in cohort 3. Multimodal US showed good diagnostic performance in predicting breast malignancy of BI-RADS category 4 lesions. Although the loss of sensitivity was existing, the addition of multimodal US to US BI-RADS could improve the specificity in BI-RADS category 4 lesions, which reduced unnecessary biopsies.

Objectives To compare the imaging findings of Bowen's disease (BD) between ultrasound biomicroscopy (UBM) and conventional high-frequency ultrasound (HFUS). Methods A total of 29 pathologically proven BD lesions in 28 patients were retrospectively enrolled in the study, and all were after surgery. All the lesions were imaged with both UBM and HFUS. The imaging features on HFUS and UBM were analyzed and compared. The diagnostic results of ultrasound for BD were referenced with pathology results. Results All the 29 (100%) BD lesions appeared hypoechogenicity, solid component, and superficial hyperechoic layer (ie, keratinization) on both UBM and HFUS. The typical imaging feature of BD lesions, that was, infiltration depth confined to the epidermis, was visualized in 25 (86.2%, 25/29) lesions on UBM whereas 15 (51.7%, 15/29) on HFUS (P = .002). A "wave sign," which corresponds to the surface keratinization of BD lesion, was visualized in 17 (58.6%, 17/29) of BD lesions on UBM whereas 6 (20.7%, 6/29) on HFUS (P = .001). UBM and HFUS correctly diagnosed 25 (86.2%, 25/29) and 15 (51.7%, 15/29) BD lesions, respectively (P = .002). Conclusions Bowen's disease has some typical imaging features on US. The "wave sign" of the superficial hyperechoic layer and the clear borderline between the tumor in epidermis and the slightly hyperechoic dermis layer are better depicted by UBM in comparison with HFUS, which leads to a more accurate diagnosis of BD. UBM has potential to be used as a diagnostic tool for characterization of BD on account of its high resolution.

To investigate the value of ultrasound (US) and clinicopathological features of papillary thyroid cancer (PTC) in predicting Telomerase Reverse Transcriptase (TERT) promoter mutations. Preoperative US images of 351 surgically confirmed PTCs were evaluated in terms of PTCs size and US features. The basic clinicopathological features were also retrieved. Univariate and multivariate analyses were performed to identify the risk factors for TERT promoter mutations. A scoring system was developed based on the cumulative number of risk factors. The area under the receiver operating characteristic curve (AUC) and cut-off value were calculated to evaluate the diagnostic performance of the scoring system for predicting TERT promoter mutations. TERT promoter mutations were found in 4.84% (17/351) of patients with PTCs. Patient age >50 years (OR: 6.244, P = 0.006), multifocality (OR: 21.071, P = 0.022), taller-than-wide shape (OR: 4.934, P = 0.029), microlobulated margin (OR: 4786, P = 0.032), and capsule contact or involvement (OR: 4.668, P = 0.030) were independent risk factors for TERT promoter mutations. TERT promoter mutations were relevant to more suspicious US and clinicopathological features than TERT promoter wild-type PTC (median, 4 vs. 1, P

Thyroid nodules have a high prevalence and a small percentage is malignant. Many non-invasive methods have been developed with the help of the Internet of Things to improve the detection rate of malignant nodules. These methods can be roughly categorized into two classes: radiomics based and deep learning based approaches. In general, convolutional neural networks based deep learning methods have achieved promising performance in many medical image analysis and classification applications; however, no existing comparison has been done between radiomics based and deep learning based approaches. Therefore, in this paper, we aim to compare the performance of radiomics and deep learning based methods for the classification of thyroid nodules from ultrasound images. On one hand, we developed a radiomics based method, which consists of extracting high throughput 302-dimensional statistical features from pre-processed images. Then dimension reduction was performed using mutual information and linear discriminant analysis respectively to achieve the final classification. On the other hand, a deep learning based method was also developed and tested by pre-training a VGG16 model with fine-tuning. Ultrasound images including 3120 images (1841 benign nodules and 1393 malignant nodules) from 1040 cases were retrospectively collected. The dataset was divided into 80% training and 20% testing data. The highest accuracies yielded on the testing data for radiomics and deep learning based methods were 66.81% and 74.69%, respectively. A comparison result demonstrated that the deep learning based method can achieve a better performance than using radiomics.

BACKGROUND: To evaluate whether MicroPure imaging, an ultrasound (US) image-processing technique with computer-aided analysis, can quantitatively detect crystal dissolution during urate-lowering therapy (ULT) in gout. METHODS: This was a prospective study of gout patients requiring ULT. The first metatarsophalangeal joints were examined using US and MicroPure before and after 3 months of ULT. Elementary lesions of gout, including the double contour sign (DCS), aggregates, tophi, erosion, and other US features were recorded at baseline and 3 months. MicroPure imaging features were automatically calculated by a self-developed software. Patients were divided into goal-achieved and goal-not-achieved groups according to their urate levels at 3 months. The US and MicroPure imaging features of the two groups were analyzed at baseline and 3 months. RESULTS: A total of 55 consecutive patients were enrolled (25: goal-achieved group; 30: goal-not-achieved group). US findings demonstrated that the power Doppler signal grade decreased at 3 months, regardless of the group (both P0.05). CONCLUSIONS: In comparison with B-mode US, computer-aided MicroPure imaging can sensitively and quantitatively detect aggregate dissolution during effective ULT after only 3 months of treatment.

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy., Immunotherapy for the treatment of cancer can be complicated by side effects and poor efficacy. Here, the authors use a nanoparticle-based approach in combination with a TLR7 agonist and sonodynamic therapy, and find that when used together with anti-PD-L1, tumour formation and metastases are impacted.

Purpose: This prospective study explored the value of synchronous tele-ultrasound (US) to aid doctors inexperienced in US with breast US examinations.Methods: In total, 99 patients were enrolled. Two trainee doctors who were inexperienced in US (trainee A [TA] and trainee B [TB]) and one doctor who was an expert in US completed the US examinations sequentially. TA completed the US examinations independently, while TB was instructed by the expert using synchronous tele-US. Subsequently, the expert performed on-site US examinations in person. Separately, they selected the most clinically significant nodule as the target nodule. Consistency with the expert and image quality were compared between TA and TB to evaluate tele-US. Furthermore, TB and the patients evaluated tele-US through questionnaires.Results: TB demonstrated higher consistency with the expert in terms of target nodule selection than TA (93.3% vs. 63.3%, P0.75) with the expert on five US features (5/9, 55.6%), while TA only did so for one (1/9, 11.1%) (P=0.046). TB’s image quality was higher than TA’s in gray value, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (P=0.018, P

OBJECTIVES Pathological invasion level of extramammary Paget disease (EMPD) is strongly related with its risk staging, treatment, and prognosis. However, the current evaluation before treatments fails to evaluate pathological invasion level of EMPD. High-frequency ultrasound (HFUS) may play a key role to solve this problem. The purpose was to explore the performance of HFUS in the evaluation of pathological invasion level of EMPD. METHODS Sixty pathologically proven EMPD patients were retrospectively enrolled and divided into 2 groups as follows: in situ in the epidermis (IE) (n = 42) and invasion into the dermis or subcutaneous (ID) (n = 18) groups. Clinical and HFUS features were compared between the 2 groups. RESULTS Between the 2 groups, HFUS features (lesion shape, internal echogenicity and echotexture, surface shape, epidermal hyperechoic layer on the surface, the "pseudopod sign", and color Doppler ultrasound features) and clinical features were comparable (all P >.05). Tumor growth pattern significantly differed between the 2 groups (P

BACKGROUND Esophageal varices (EV) are the most fatal complication of chronic hepatitis B (CHB) related cirrhosis. The prognosis is poor, especially after the first upper gastrointestinal hemorrhage. AIM To construct nomograms to predict the risk and severity of EV in patients with CHB related cirrhosis. METHODS Between 2016 and 2018, the patients with CHB related cirrhosis were recruited and divided into a training or validation cohort at The First Affiliated Hospital of Wenzhou Medical University. Clinical and ultrasonic parameters that were closely related to EV risk and severity were screened out by univariate and multivariate logistic regression analyses, and integrated into two nomograms, respectively. Both nomograms were internally and externally validated by calibration, concordance index (C-index), receiver operating characteristic curve, and decision curve analyses (DCA). RESULTS A total of 307 patients with CHB related cirrhosis were recruited. The independent risk factors for EV included Child-Pugh class [odds ratio (OR) = 7.705, 95% confidence interval (CI) = 2.169-27.370, P = 0.002], platelet count (OR = 0.992, 95%CI = 0.984-1.000, P = 0.044), splenic portal index (SPI) (OR = 3.895, 95%CI = 1.630-9.308, P = 0.002), and liver fibrosis index (LFI) (OR = 3.603, 95%CI = 1.336-9.719, P = 0.011); those of EV severity included Child-Pugh class (OR = 5.436, 95%CI = 2.112-13.990, P < 0.001), mean portal vein velocity (OR = 1.479, 95%CI = 1.043-2.098, P = 0.028), portal vein diameter (OR = 1.397, 95%CI = 1.021-1.912, P = 0.037), SPI (OR = 1.463, 95%CI = 1.030-2.079, P = 0.034), and LFI (OR = 3.089, 95%CI = 1.442-6.617, P = 0.004). Two nomograms (predicting EV risk and severity, respectively) were well-calibrated and had a favorable discriminative ability, with C-indexes of 0.916 and 0.846 in the training cohort, respectively, higher than those of other predictive indexes, like LFI (C-indexes = 0.781 and 0.738), SPI (C-indexes = 0.805 and 0.714), ratio of platelet count to spleen diameter (PSR) (C-indexes = 0.822 and 0.726), King's score (C-indexes = 0.694 and 0.609), and Lok index (C-indexes = 0.788 and 0.700). The areas under the curves (AUCs) of the two nomograms were 0.916 and 0.846 in the training cohort, respectively, higher than those of LFI (AUCs = 0.781 and 0.738), SPI (AUCs = 0.805 and 0.714), PSR (AUCs = 0.822 and 0.726), King's score (AUCs = 0.694 and 0.609), and Lok index (AUCs = 0.788 and 0.700). Better net benefits were shown in the DCA. The results were validated in the validation cohort. CONCLUSION Nomograms incorporating clinical and ultrasonic variables are efficient in noninvasively predicting the risk and severity of EV.

Objectives: The aim of this study was to develop an ultrasound consolidated score (UCS) in determining the activity of Crohn’s disease (CD) and evaluate it with reference to simple endoscopic score (SES). Methods: From June 2014 to June 2017, 66 patients with CD were retrospectively enrolled in this study. Each patient underwent endoscopy and transabdominal ultrasound (US) examination. The morphological symmetry, echogenicity of bowel wall, bowel wall layer structure, echogenicity of peri-bowel fat, bowel wall thickness (BWT), and Limberg type on power Doppler US were assessed with transabdominal US, and an UCS scoring system was developed based on these characteristics. Endoscopic results were used as the reference standard and SES was calculated to determine the CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance for determining CD activity and the correlation between UCS and SES was assessed using Spearman correlation analysis. Results: 330 intestinal segments in 66 patients were included. The UCS of the segments in the remission phase ranged from 3.0 to 9.0 (mean, 3.6 ± 0.9) whereas in the active phase from 3.0 to 20.0 (mean, 10.6 ± 4.0) (p < 0.001). The cut-off value of UCS was 6. The associated area under ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.980, 88.3%, 95.5%, 93.8%, 91.3%, and 92.3%, respectively. The correlation coefficient between UCS and SES was 0.90, which was higher than the correlation coefficient of 0.83 between BWT and SES. Conclusions: The newly developed UCS with transabdominal US has a good performance and potentially provides an effective alternative for evaluating the activity of CD. Advances in knowledge: UCS is an effective method to evaluate the activity of CD because it provides comprehensive information of the disease. Therefore, it could be employed as an alternative for diagnosis of CD.

Objectives The purpose of this study was to establish a scoring system for predicting axillary lymph node metastasis (ALNM) in patients with breast invasive ductal carcinoma with negative axillary ultrasound (US) results. Methods In this retrospective study, 156 breast invasive ductal carcinoma lesions from 156 women were retrospectively enrolled. The features of conventional US and contrast-enhanced ultrasound (CEUS) qualitative enhancement patterns and quantitative enhancement parameters were analyzed. Subsequently, a scoring system was created by a multivariate logistic regression analysis. Results The results found that 60 patients (38%) showed ALNM. A scoring system was defined as risk score = 1.75 × (if lesion size ≥20 mm) + 1.93 × (if uncircumscribed margin shown on conventional US) + 1.77 × (if coarse or twisting penetrating vessels shown on CEUS). When the risk scores were less than 1.75, 1.75 to 1.93, 1.94 to 3.70, and 3.70 or higher, the risk rates of ALNM were 0% (0 of 9), 10.7% (5 of 46), 29.2% (14 of 48) and 77.4% (41 of 53), respectively. In comparison with conventional US alone, the scoring system using the combination of conventional US and CEUS showed better discrimination ability in terms of the area under the curve (0.830 versus 0.777; P = .037). Conclusions A scoring system based on conventional US and CEUS may improve the prediction of ALNM.

OBJECTIVE To compare the diagnostic performance and the unnecessary biopsy rates for recommending fine needle aspiration (FNA) of Thyroid Imaging Reporting and Data Systems proposed by American College of Radiology (ACR TI-RADS), American Thyroid Association (ATA) guidelines, TI-RADS proposed by Kwak (Kwak TI-RADS), and Korean Thyroid Association/Korean Society of Thyroid Radiology (KTA/KSThR) guidelines for malignancy risk stratification of thyroid nodules (TNs). METHODS The study included 1271 TNs whose cytologic results or surgical pathologic findings were available. Ultrasound images of these TNs were retrospectively reviewed and categorized according to the four guidelines. The diagnostic performances and the unnecessary biopsy rates for recommending FNA of the four guidelines were evaluated. RESULTS After multivariate analysis, the most significant independent predictor for malignancy was hypoechogenicity/marked hypoechogenicity (OR: 9.37, 95% CI: 5.40-16.26) (P

OBJECTIVE With the fast development of artificial intelligence techniques, we proposed a novel two-stage multi-view learning framework for the contrast-enhanced ultrasound (CEUS) based computer-aided diagnosis for liver tumors, which adopted only three typical CEUS images selected from the arterial phase, portal venous phase and late phase. MATERIALS AND METHODS In the first stage, the deep canonical correlation analysis (DCCA) was performed on three image pairs between the arterial and portal venous phases, arterial and delayed phases, and portal venous and delayed phases respectively, which then generated total six-view features. While in the second stage, these multi-view features were then fed to a multiple kernel learning (MKL) based classifier to further promote the diagnosis result. Two MKL classification algorithms were evaluated in this MKL-based classification framework. We evaluated proposed DCCA-MKL framework on 93 lesions (47 malignant cancers vs. 46 benign tumors). RESULTS The proposed DCCA-MKL framework achieved the mean classification accuracy, sensitivity, specificity, Youden index, false positive rate, and false negative rate of 90.41 ± 5.80%, 93.56 ± 5.90%, 86.89 ± 9.38%, 79.44 ± 11.83%, 13.11 ± 9.38% and 6.44 ± 5.90%, respectively, by soft margin MKL classifier. CONCLUSION The experimental results indicate that the proposed DCCA-MKL framework achieves best performance for discriminating benign liver tumors from malignant liver cancers. Moreover, it is also proved that the three-phase CEUS image based CAD is feasible for liver tumors with the proposed DCCA-MKL framework.

To evaluate the value of ultrasound (US) in differentiating the acute phase of gout from the intercritical phase, particularly using shear wave elastography (SWE). 57 gout patients were prospectively enrolled and divided into acute phase and intercritical phase groups. The patients underwent US and SWE examinations for the first metatarsophalangeal joints with the same protocol. Maximum synovial thickness was measured. US features were reviewed by two radiologists independently. The maximum (Emax) and mean (Emean) elastic moduli of synovium were calculated. Diagnostic performances of US, SWE and combined US and SWE were evaluated. US findings demonstrated that the colour Doppler flow signal grade in the acute phase was higher than that in the intercritical phase (p = 0.001), whereas no differences were found for B-mode US features between the two groups (all p > 0.05). For SWE, Emax and Emean were significantly higher in the intercritical phase than in the acute phase (both p < 0.001). The areas under the receiver operating characteristic curve (AUROCs) were 0.494–0.553 for B-mode US, 0.735 for colour Doppler US (CDUS), 0.887 for Emax and 0.882 for Emean. The combination of CDUS and SWE increased the AUROC, sensitivity and accuracy significantly in comparison with CDUS alone (all p < 0.001). However, the combined set did not show stronger diagnostic performance in comparison with SWE alone. SWE increases the diagnostic performance in differentiating the acute phase of gout from the intercritical phase in comparison with conventional US. • Colour Doppler flow signal grade is higher in acute phase of gout than in intercritical phase. • SWE demonstrates that synovium stiffness is higher in intercritical phase of gout than in acute phase. • SWE increases diagnostic performance in differentiating acute phase of gout from intercritical phase in comparison with conventional US.

To compare the sampling efficiency and diagnostic performance of ultrasound (US)-guided fine-needle aspiration cytology (FNAC) and fine-needle non-aspiration cytology (FNNAC) for thyroid nodules.629 thyroid nodules in 629 cases (477 females, 152 males) were randomly subjected to FNAC or FNNAC from Jun 2014 to Feb 2015. Diagnostic performance was calculated in reference to the histological findings or follow-up results.629 patients (152 men, 477 women) with 629 thyroid nodules were enrolled in the study. Pathological results were obtained in 173 nodules and benign nodules at FNA with more than six months' follow-up were found in 65 nodules. Tumor size for FNAC ranges from 3.0 to 51.0 mm (mean±SD; 10.2±6.9 mm); whereas FNNAC (2.0-43.0 mm; 11.9±7.7 mm). Non-diagnostic results were found in 7.59% (24/316) of FNNAC procedures and 7.59% (25/313) of FNAC (P 0.05). Determinate and indeterminate results were found in 50.63% (160/316) and 41.77% (132/316) of FNNAC procedures, whereas 58.15% (182/313) and 33.87% (106/313) of FNAC (P 0.05). In order to obtain determinate cytological results, FNAC might be more suitable than FNNAC for diagnosis of nodules with hypovascularity (51.38% vs. 41.78%, P 0.05) and macrocalcifications (9.72% vs. 6.50%, P 0.05). No US and Color-Doppler US characteristics, such as the presence of hypervascularity (P 0.05), microcalcifications (P 0.05), internal component (P 0.05), or size(P 0.05), were significantly different to obtain determinate cytological results between the FNAC and FNNAC groups. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of FNAC and FNNAC were as follows: 96.67% vs. 100%, 89.74% vs. 96.5%, 87.88% vs. 96.97%, 97.22% vs. 100%, 92.75% vs.98.36%, respectively (all P 0.05).Both FNAC and FNNAC are effective for diagnosis of thyroid nodules. However, FNAC is more effective than FNNAC to acquire determinate cytological results for nodules which US present hypovascularity and macrocalcifications.

To assess the factors associated with initial incomplete ablation (ICA) after radiofrequency ablation for benign thyroid nodules (BTNs).69 BTNs (mean volume 6.35±5.66 ml, range 1.00-25.04 ml) confirmed by fine-needle aspiration cytology (FNAC) in fifty-four patients were treated with ultrasound-guided percutaneous radiofrequency ablation (RFA) and the local treatment efficacy was immediately assessed by intra-procedural contrast-enhanced ultrasound (CEUS). The RFA was performed with a bipolar electrode (CelonProSurge 150-T20, output power: 20 W). CEUS was performed with a second generation contrast agent under low acoustic power (i.e. coded phase inversion, CPI). Characteristics of clinical factors, findings on conventional gray-scale ultrasound, color-Doppler ultrasound, and CEUS were evaluated preoperatively. Factors associated with initial ICA and initial ICA patterns on CEUS were assessed. Volume reduction ratios (VRRs) of ICA nodules were compared with those with complete ablation (CA).The RFA procedures were accomplished with a mean ablation time and mean total energy deposition of 11.13±3.39 min (range, 5.38-22.13 min) and 12612±4466 J (range, 6310-26130 J) respectively. CEUS detected initial ICA in 21 of 69 (30.8%) BTNs and 16 (76.2%) of the 21 BTNs with initial ICA achieved CA after additional RFA, leading to a final CA rate of 92.8% (64/69). The factors associated with initial ICA were predominantly solid nodule, nodule close to danger triangle area, nodule close to carotid artery, and peripheral blood flow on color-Doppler ultrasound (all P 0.05). The mean VRRs of all BTNs were 23.4%, 54.4% and 81.9% at the 1-, 3- and 6-month follow-up, respectively. All BTNs achieved therapeutic success in this series in that all had VRRs of50% at the 6-month follow-up, among which 7 nodules (10.1%) had VRRs of90%. There were significant differences in VRRs between ICA nodules and CA nodules at the 3- and 6-month follow-up (all P 0.05).The factors associated with initial ICA after RFA for BTNs were predominantly solid nodules, nodule close to danger triangle area, nodule close to carotid artery, and peripheral blood flow on color-Doppler ultrasound. CEUS assists quick treatment response evaluation and facilitates subsequent additional RFA and final CA of the nodules. Nodules with CA achieve a better outcome in terms of VRR in comparison with those with ICA.

Objectives To investigate the diagnostic performance of a 2-dimensional shear wave elastographic technique (Virtual Touch tissue imaging and quantification [VTIQ]; Siemens Medical Solutions, Mountain View, CA) for predicting thyroid malignancy. Methods A total of 302 thyroid nodules underwent conventional sonography and VTIQ before fine-needle aspiration examination or surgery. Compared with histopathologic or cytologic results in combination with follow-up, the diagnostic performance of various shear wave speed (SWS) indices (minimum [SWSmin], maximum [SWSmax], and mean [SWSmean]) on VTIQ as well as conventional sonographic features for predicting thyroid malignancy was evaluated in all of the nodules. Results Sixty-five malignant and 237 benign thyroid nodules were histopathologically or cytologically confirmed. All SWS indices on VTIQ were lower in benign nodules than thyroid malignancy (all P

Ultrasonography is a common modality for diagnosing thyroid nodules. Computer-aided classification of benign and malignant thyroid nodules in the ultrasound images is meaningful. A key challenge in this issue is that a lot of ultrasound images without obvious benign or malignant features are hindering deep learning model to extract effective features. Here, a novel method using two combined classification modules is proposed to separate and classify those images. Firstly, we adopt multi-fold cross-validation based a CNN model to pick out ultrasound images that hard to recognize. Then we add new labels to those images and put them back to the dataset that will be trained with the CNN model to form a tripartite classification module. Finally, a binary classification module will be trained exclusively to discriminate those obscure images. Experimental results on 4148 ultrasound images show that the proposed method lead to excellent performance, with an accuracy of 0.804, which demonstrate the value of this method.

OBJECTIVE To investigate the stiffness distribution in the ablated zone after radiofrequency ablation (RFA), we used a device called tissue elastometer based on gross liver samples. MATERIALS AND METHODS: Twelve freshly excised porcine livers were subject to RFA under a same setup to form elliptic ablated samples. Each sample was cut open for gross examination, and then the surface of the section plane was sliced into one piece for Young's modulus test using the tissue elastometer. Five test points along the long- and short-axis on each piece were selected to evaluate stiffness distribution respectively. Among them, four points distributed equidistantly from center to boundary in the ablated zone and one was in the unablated zone. RESULTS In the ablated zone, we found the Young's moduli were significantly different among the four test points both in long- (F = 99.04, p

OBJECTIVES The purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high-frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings. METHODS In this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS. RESULTS Ultrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P

With the increasing incidence rate of thyroid cancer, the diagnosis of thyroid nodules has become an important task. In this paper, we designed a deep neural network (DNN) to classify whether a thyroid nodule is benign or malignant, and proposed a structure which combines local binary pattern (LBP) with deep learning. Our method mitigates the effects of overfitting in medical image diagnosis tasks. With well-designed transfer leaning, we achieve an accuracy of 85% on our own ultrasound thyroid dataset. To ensure the reliability of our experiments, all examples are estimated by experts in Shanghai Tenth People’s Hospital using fine needle analysis (FNA), which is a gold standard for thyroid nodules diagnosis. The experimental results show that combinations of the traditional medial image features can help the deep learning network get more semantic information from low-level inputs.

Aim To evaluate the diagnostic performance of parametric imaging with contrast-enhanced ultrasound(CEUS) for differentiating hepatocellular carcinoma(HCC) from metastatic liver cancer(MLC). Methods 30 HCCs (mean diameter, 3.6±1.3 cm; range, 2.1-5.0 cm) and 30 MLCs (mean diameter, 2.8±1.5 cm; range, 1.2-5.0 cm) pathologically diagnosed or confirmed by clinical criteria that underwent CEUS were randomly included. CEUS was carried out using a multifrequency transducer (2-4 MHz) and a bolus injection of 2.4 mL SonoVue. The CEUS clips of the targeted lesion were recorded continuously for 6 minutes. By analyzing CEUS clips, parametric image could be obtained using the SonoLiver® software automatically. Quantitative parameters were compared between HCC and MLC groups. Receiver operating characteristic (ROC) curve analysis was further performed on parameters with significant difference between two groups. Results On parametric imaging, the maximum intensity, rise time, time to peak, mean transit time and washout time for HCC and MLC were 185.6±148.0 vs. 95.2±58.6 (P = 0.003), 25.7±6.3 s vs. 23.8±8.8 s (P = 0.341), 30.7±7.9 s vs. 27.8±10.5 s (P = 0.246), 90.2±45.7 s vs. 89.3±40.3 s (P = 0.805), 63.4±29.5 s vs. 37.2±33.8 s (P = 0.005), respectively. ROC analysis was further performed for washout time and it showed a cut-off point of 43.765 s for the differentiation between HCC and MLC, with the AUC value of 0.780 (95% CI: 0.646-0.914). The corresponding diagnostic specificity, sensitivity and accuracy were 72.0%, 84.6% and 78.4% respectively. Conclusions Parametric imaging of CEUS can display perfusion effects of HCC and MLC objectively and visually and washout time may serve as a useful parameter on the differential diagnosis between HCC and MLC.

The purpose of the study was to evaluate the value of 2-D shear wave elastography (SWE) of virtual touch tissue imaging quantification (VTIQ) for ultrasound (US) Breast Imaging-Reporting and Data System (BI-RADS) category 4 lesions. One hundred sixteen lesions were subject to conventional US, conventional strain elastography (SE) of elasticity imaging (EI), acoustic radiation force impulse (ARFI)-induced SE of virtual touch tissue imaging (VTI) and VTIQ before biopsies. Of the 116 lesions, 69 (59.5%) were benign and 47 (40.5%) were malignant. Significant differences were found between benign and malignant lesions in EI score, VTI score and shear wave speed (SWS) on VTIQ (both p

// Bao-Ding Chen 1,2,3,4,5 , Hui-Xiong Xu 1,2,3,4 , Yi-Feng Zhang 1,2,3,4 , Bo-Ji Liu 1,2,3,4 , Le-Hang Guo 1,2,3,4 , Dan-Dan Li 1,2,3,4 , Chong-Ke Zhao 1,2,3,4 , Xiao-Long Li 1,2,3,4 , Dan Wang 1,2,3,4 and Shuang-Shuang Zhao 5 1 Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai, China 2 Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Clinical College of Nanjing Medical University, Shanghai, China 3 Thyroid Institute, Tongji University School of Medicine, Shanghai, China 4 Shanghai Center of Thyroid Diseases, Shanghai, China 5 Department of Medical Ultrasound, Affiliated Hospital of Jiangsu University, Zhenjiang, China Correspondence to: Hui-Xiong Xu, email: // Keywords : thyroid nodule, calcification, ultrasound, shear-wave elastography, point shear-wave measurement Received : June 30, 2016 Accepted : August 26, 2016 Published : August 31, 2016 Abstract Conventional ultrasound cannot satisfactorily distinguish malignant and benign thyroid nodules. Shear-wave elastography (SWE) can evaluate tissue stiffness and complement conventional ultrasound in diagnosing malignant nodules. However, calcification of nodules may affect the results of SWE. The purposes of this study are to compare the differences of shear-wave speed (SWS) measurement among different calcification groups and compare the diagnostic performance between using a single uniform SWS cutoff value and multiple individual calcification-specific cutoff values using technique of point SWS measurement. We retrospectively identified 517 thyroid nodules (346 benign and 171 malignant nodules) examined by conventional ultrasound and point SWS measurement. There were 177 non-calcified, 159 micro-calcified and 181 macro-calcified nodules. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC) was computed. The mean SWS in malignant nodules more than doubled that of benign nodules (4.81±2.03 m/s vs. 2.29±0.99 m/s, p 2.42 m/s), micro- (SWS >2.88 m/s) and macro-calcification (SWS >3.59 m/s) nodules in the whole group, the AUC was 0.859 (95% confidence interval [CI], 0.826-0.888), which was significantly better than the AUC of 0.816 (95% CI, 0.780-0.848) if a single uniform cutoff value (SWS >2.72 m/s) was applied to all the nodules regardless of calcification status (p=0.011). The cutoff values of SWS for different calcified nodules warrant future prospective validation.

OBJECTIVES To evaluate the additional value of the area ratio on Virtual Touch tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA) for diagnosis of thyroid nodules referred to surgery. METHODS From April 2013 to February 2014, 205 consecutive patients with 225 histologically proven thyroid nodules were enrolled in this retrospective study. Virtual Touch tissue imaging and area ratio measurements were performed for each nodule. The area ratio was defined as the area of the nodule on VTI divided by the area on B-mode sonography. Nodule stiffness on VTI was graded from I (soft) to VI (hard). Receiver operating characteristic curve analyses of VTI, area ratio, and the combination of VTI and area ratio were performed. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and Youden index were also evaluated. RESULTS By receiver operating characteristic curve analyses, the cutoff values were VTI grade IV and area ratio of 1.09, respectively. Nodules with VTI grade IV or higher or area ratio of 1.09 or higher were more likely to be malignant. The sensitivity, specificity, accuracy, PPV, NPV, and Youden index were 78.6%, 92.3%, 88.0%, 82.1%, 90.5%, and 0.709 for VTI and 81.4%, 87.1%, 85.3%, 74.0%, 91.2%, and 0.685 for area ratio (all P > .05). However, when using the criterion of VTI grade IV or higher and area ratio of 1.09 or higher as a combination, the sensitivity, specificity, accuracy, PPV, NPV, and Youden index increased to 94.3%, 97.4%, 96.4%, 94.3%, 97.4%, and 0.917 (all P< .05 compared to VTI or area ratio alone, except for specificity between VTI and the combination). CONCLUSIONS The diagnostic performance of VTI grading and the area ratio for differentiation between benign and malignant thyroid nodules is equivalent. The performance is further improved with a combination of VTI grading and area ratio analysis.

Studies have shown the potential of nanomaterials for the accurate and early detection of cancer. The aim of the present study was to design and evaluate the value of prostate-specific membrane antigen (PSA)-targeted manganese oxide–mesoporous silica nanoparticles (Mn–Msns) for the detection of prostate cancer. Mn–Msns were prepared, and then conjugated with the PSA antibody and Cy7 to create the multimodality PSA-Mn-Msn-Cy7. Their particle size, zeta potential, stability and magnetic resonance imaging (MRI) features of the nanoparticles were characterized. Optical and MR imaging were evaluated in cell and tumor-bearing mouse models. The Mn in tissues was measured by inductively coupled plasma mass spectrometry. The fabricated nanoparticles were stable and showed good T1relaxivity. The targeted nanoparticles accumulated to a great extent in prostate cancer cells in vitro but not in noncancerous cells. In vivo studies further demonstrated a targeted distribution of PSA-Mn-Msn-Cy7 to cancer tissues as shown by high optical and T1 signals. The targeted distribution was also confirmed by determining the Mn content in the cancer tissues. Our data demonstrate that PSA targeted fluorescence and MR dual-functional nanoparticle can visualize prostate cancer and can be used as NIRF/MR contrast agents.

Contrast-enhanced ultrasound (CEUS) is a valuable imaging modality for diagnosis of liver cancers. However, the complexity of CEUS-based diagnosis limits its wide application, and the B-mode ultrasound (BUS) is still the most popular diagnosis modality in clinical practice. In order to promote BUS-based computer-aided diagnosis (CAD) for liver cancers, we propose a learning using privileged information (LUPI) based CAD with BUS as the diagnosis modality and CEUS as PI. Particularly, the multimodal restricted Boltzmann machine (MRBM) works as a LUPI paradigm. That is, one BUS image and three CEUS images from the arterial phase, portal venous phase and delayed phase, respectively, are used to train three multimodal restricted Boltzmann machine (MRBM) models during training stage, but only the BUS data will be fed to MRBM to generate new feature representation at testing phase. A multiple empirical kernel learning machine (MEKLM) classifier is then performed on three new feature vectors from three MRBM models for classification of liver cancers. The experimental results show that the proposed MRBM-MEKLM algorithm outperforms all the compared algorithms, suggesting the effectiveness of the proposed LUPI-based CAD for liver cancer.

EVA1A (also known as transmembrane protein 166) is a transmembrane protein involved in the regulation of autophagy that acts as an adaptor protein to recruit or bind proteins in the lysosome or endoplasmic reticulum. In the present study, we identified EVA1A as a target of microRNA-125b (miR-125b), a member of a highly conserved family of miRNAs that has been proposed as a biomarker for hepatocellular carcinoma (HCC). Analysis of oxaliplatin-sensitive and oxaliplatin-resistant HCC cell lines showed that miR-125b is downregulated in resistant cells and its overexpression in sensitive cells decreased resistance to oxaliplatin by inhibiting cell proliferation, migration and epithelial-mesenchymal transition (EMT). EVA1A expression was shown to be upregulated in tissue samples from oxaliplatin-resistant HCC patients, and its ectopic expression partially induced autophagy and reversed the effect of miR-125b on inhibiting the growth of oxaliplatin-resistant cell lines and xenograft tumors. Taken together, our results suggest that miR-125b plays a role in the resistance of HCC cells to chemotherapy via a mechanism involving the downregulation of EVA1A-mediated autophagy.

To prospectively evaluate the diagnostic performance of three-dimensional (3D) shear wave elastography (SWE) for breast lesions with quantitative stiffness information from transverse, sagittal and coronal planes.Conventional ultrasound (US), two-dimensional (2D)-SWE and 3D-SWE were performed for 122 consecutive patients with 122 breast lesions before biopsy or surgical excision. Maximum elasticity values of Young's modulus (Emax) were recorded on 2D-SWE and three planes of 3D-SWE. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, 2D-SWE and 3D-SWE were evaluated. Two combined sets (i.e., BI-RADS and 2D-SWE; BI-RADS and 3D-SWE) were compared in AUC. Observer consistency was also evaluated.On 3D-SWE, the AUC and sensitivity of sagittal plane were significantly higher than those of transverse and coronal planes (both P0.05). Compared with BI-RADS alone, both combined sets had significantly (P0.05) higher AUCs and specificities, whereas, the two combined sets showed no significant difference in AUC (P0.05). However, the combined set of BI-RADS and sagittal plane of 3D-SWE had significantly higher sensitivity than the combined set of BI-RADS and 2D-SWE.The sagittal plane shows the best diagnostic performance among 3D-SWE. The combination of BI-RADS and 3D-SWE is a useful tool for predicting breast malignant lesions in comparison with BI-RADS alone.

To investigate the value of combined conventional ultrasound (US), strain elastography (SE) and acoustic radiation force impulse (ARFI) elastography for prediction of cervical lymph node metastasis (CLNM) in papillary thyroid cancer (PTC).A consecutive series of 203 patients with 222 PTCs were preoperatively evaluated by US, SE, and ARFI including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ). A multivariate analysis was performed to predict CLNM by 22 independent variables. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance.Multivariate analysis demonstrated that VTI area ratio (VAR) 1 was the best predictor for CLNM, followed by abnormal cervical lymph node (ACLN), capsule contact, microcalcification, capsule involvement, and multiple nodules (all P 0.05). ROC analyses of these characteristics showed the areas under the curve (Az), sensitivity, and specificity were 0.600-0.630, 47.7 %-93.2 %, and 26.9 %-78.4 % for US, respectively; and they were 0.784, 83.0 %, and 73.9 %, respectively, for VAR 1. As combination of US characteristics with and without VAR, the Az, sensitivity, and specificity were 0.803 and 0.556, 83.0 % and 100.0 %, and 77.6 % and 11.2 %, respectively (P 0.001).ARFI elastography shows superior performance over conventional US, particularly when combined with US, in predicting CLNM in PTC patients.• Conventional ultrasound is useful in predicting cervical lymph node metastasis preoperatively. • Virtual touch tissue imaging area ratio is the strongest predicting factor. • Predictive performance is markedly improved by combining ultrasound characteristics with VAR. • Acoustic radiation force impulse elastography may be a promising complementary tool.

Prostate sarcoma is a rare malignancy with an extremely poor prognosis. The extremely low morbidity and atypical clinical symptoms contribute to a missed diagnosis. The typical features of prostate sarcoma in transrectal ultrasound (US) and magnetic resonance imaging, such as a markedly enlarged volume and irregular prostatic contours, cannot usually be found until dysuria or even uroschesis occurs, and may then be too late to treat. However, there appears to no specific tumor marker for the disease in the serum. The present study reports a case of a young male patient who was diagnosed with prostate rhabdomyosarcoma. This was, to the best of our knowledge, the first case of this diagnosis using contrast-enhanced US (CEUS) when the symptoms were not severe. In this case, the intralesional non-enhancement areas and rim-like hyper-enhancement around the lesion were considered to be the main CEUS features of prostate rhabdomyosarcoma. The present study also reviews the associated literature.

To evaluate the value of fusion imaging with post-treatment contrast-enhanced ultrasound (CEUS) and pre-treatment contrast-enhanced CT/MRI (CECT/CEMRI) in evaluating ablative safety margin after percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for liver cancers.34 consecutive patients with 47 liver lesions who had undergone RFA were included. Fusion imaging with post-treatment CEUS and pre-treatment CECT/CEMRI was carried out to evaluate local treatment response and ablative safety margin within 1-3 days after RFA. The minimal ablative safety margins of the ablation zones were recorded. The complete response (CR) rate was calculated with reference to CECT/CEMRI results 1 month after RFA. The local tumour progression (LTP) was also recorded.Of the 47 ablation zones, 47 (100%) were clearly depicted with CEUS-CECT/CEMRI fusion imaging, 36 (76.6%) with US-CECT/CEMRI fusion imaging and 21 (44.7%) with conventional US (both p0.001). The minimal ablative safety margins were great than or equal to 5 mm in 28 ablation zones, between 0 and 5 mm in 15, and less than 0 mm in 4. For the four lesions without enough ablative safety margin, three were referred to follow-up because CEUS showed larger ablation zones than pre-treatment lesions and the remaining lesion was subject to additional RFA 5 days after the first RFA. The CR rate was 95.7% (45/47) with reference to CECT/CEMRI results 1 month after RFA. During 2 to 34 months follow-up, LTP was found in two (4.4%) of 45 lesions with CR. Insufficient ablative safety margin was more commonly found in those lesions with LTP than those without LTP (1/4 vs 1/43, p0.001).Fusion imaging with post-treatment CEUS and pre-treatment CECT/CEMRI can depict the ablative safety margin accurately after RFA. Inadequate ablative safety margin is associated with LTP. Depiction of ablative safety margin by fusion imaging after ablation might be considered as a routine procedure to assess the treatment response of RFA. Advances in knowledge: Fusion imaging with post-treatment CEUS and pre-treatment CECT/CEMRI is an effective method to evaluate the ablative safety margin early after RFA. Therefore, it should be recommended to be used as a routine procedure after RFA for liver cancers.

To investigate the diagnostic performance of combination of ultrasound (US) thyroid imaging reporting and data system (TI-RADS) and a new US scoring system for diagnosing thyroid nodules (TNs) with indeterminate results (Bethesda categories III, IV and V) on fine-needle aspiration (FNA) cytology. 453 patients with 453 cytologically indeterminate TNs were included in this study. Multivariate analyses were performed to construct the scoring system. The diagnostic performances of TI-RADS and the combined method were evaluated and compared. Multivariate analyses revealed that marked hypoechogenicity, taller than wide shape and absence of halo sign were independent predictors for malignancy in cytologically indeterminate TNs. Scoring system was thereafter defined as follows: risk score (RS) = 3.2 x (if marked hypoechogenicity) + 2.8 x (if taller than wide shape) + 1.3 x (if absence of halo sign). Compared with TI-RADS alone, the areas under the receiver operating characteristic curves (AUC), specificity, accuracy and positive predictive value (PPV) of the combined method increased significantly with 0.731 versus 0.569, 48.5% versus 14.1%, 76.2% versus 62.3%, and 70.9% versus 59.9%, respectively (all P

Computer-aided diagnosis (CAD) of liver cancers on contrast-enhanced ultrasound (CEUS) has attracted considerable attention in recent years. The enhancement patterns on CEUS for liver lesions consist of the arterial, portal venous and late phases. Several typical images selected from these three phases can provide reliable information basis for diagnosis of liver lesions. Therefore, we propose to develop a CAD framework for liver cancers with only one B-mode image and three typical CEUS images selected from three enhancement patterns, which simulates the clinical diagnosis mode of radiologists. Moreover, a framework of two-stage multi-view learning (TS-MVL) is proposed to perform both feature-level and classifier-level MVL for the diagnosis of liver cancers with multimodal ultrasound images. We propose to apply the nonlinear kernel matrix (NKM) algorithm to effectively fuse the features of multimodal ultrasound images, and then perform the multiple kernel boosting (MKB) algorithm to promote the predictive performance of multiple classifiers according to multi-view features. The experimental results indicate that the proposed algorithm outperforms the commonly used multi-view learning algorithms.

The contrast-enhanced ultrasound (CEUS) has been a widely accepted imaging modality for diagnosis of liver cancers. In clinical practice, several typical images selected from enhancement patterns of the arterial, portal venous and late phases can provide reliable information basis for diagnosis. In this work, we propose to develop a CEUS-based computer-aided diagnosis (CAD) for liver cancers with only three typical CEUS images selected from three phases, which simulates the clinical diagnosis mode of radiologists. In the proposed CAD, the deep canonical correlation analysis (DCCA) is first performed on three CEUS pairs between arterial and portal venous phases, arterial and late phases, respectively, due to the effectiveness of multi-view fusion of DCCA. The generated six-view features are then fed to a multiple kernel learning (MKL) classifier to further promote the predictive diagnosis result. The experimental results indicate that the proposed DCCA-MKL algorithm achieves best performance for discriminating benign liver tumors from malignant liver cancers.

OBJECTIVE To evaluate the diagnostic performance of shear wave speed (SWS) within the lesion, fat-to-lesion speed ratio (FLR), and gland-to-lesion speed ratio (GLR) for differentiation between benign and malignant breast lesions using a novel SWS imaging technique. METHODS From April 2016 to June 2016, 182 breast lesions were prospectively included in the study. For each lesion, SWS-lesion, FLR, and GLR were calculated. Pathological results were used as the reference standard. Receiver operating characteristic curves (ROC) were plotted to assess the diagnostic performance. RESULTS Of the 182 lesions, 142 (78.0%) were benign and 40 (22.0%) were malignant. Significant differences were found between benign and malignant lesions in SWS-lesion, FLR and GLR (2.12±0.64 m/s vs 3.87±1.45 m/s, 1.63±0.61 vs 2.60±1.04, and 1.33±0.39 vs 2.08±0.78, respectively. All P

Integrin β4 (ITGB4) is a transmembrane receptor involved in tumorigenesis and the invasiveness of many cancers. However, its role in hepatocellular carcinoma (HCC), one of the most prevalent human cancers worldwide, remains unclear. Here, we examined the involvement of ITGB4 in HCC and explored the underlying mechanisms. Real-time PCR and immunohistochemical analyses of tissues from 82 patients with HCC and four HCC cell lines showed higher ITGB4 levels in tumor than in adjacent non-tumor tissues and in HCC than in normal hepatic cells. Silencing of ITGB4 repressed cell proliferation, colony forming ability and cell invasiveness, whereas ectopic expression of ITGB4 promoted the proliferation and invasion of HCC cells and induced epithelial to mesenchymal transition (EMT) in parallel with the upregulation of Slug, as shown by transwell assays, WB and immunocytochemistry. Knockdown of Slug reduced cell viability inhibited invasion and reversed the effects of ITBG4 overexpression on promoting EMT, and AKT/Sox2-Nanog may also be involved. In a xenograft tumor model induced by injection of ITGB4-overexpressing cells into nude mice, ITGB4 promoted tumor growth and metastasis to the lungs. Taken together, our results indicate that ITGB4 plays a tumorigenic and pro-metastatic role mediated by Slug and suggest IGTB4 could be a prognostic indicator or a therapeutic target in patients with HCC.

To evaluate the diagnostic performance of a new two-dimensional shear wave speed (SWS) imaging (i.e. Toshiba shear wave elastography, T-SWE) in differential diagnosis of breast lesions. 225 pathologically confirmed breast lesions in 218 patients were subject to conventional ultrasound and T-SWE examinations. The mean, standard deviation and ratio of SWS values (m/s) and elastic modulus (KPa) on T-SWE were computed. Besides, the 2D elastic images were classified into four color patterns. The area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the diagnostic performance of T-SWE in differentiation of breast lesions. Compared with other quantitative T-SWE parameters, mean value expressed in KPa had the highest AUROC value (AUROC = 0.943), with corresponding cut-off value of 36.1 KPa, sensitivity of 85.1%, specificity of 96.6%, accuracy of 94.2%, PPV of 87.0%, and NPV of 96.1%. The AUROC of qualitative color patterns in this study obtained the best performance (AUROC = 0.957), while the differences were not significant except for that of Eratio expressed in m/s (AUROC = 0.863) (P = 0.03). In summary, qualitative color patterns of T-SWE obtained the best performance in all parameters, while mean stiffness (36.05 KPa) provided the best diagnostic performance in the quantitative parameters.

Purpose: To investigate the imaging features of intraductal papillary neoplasm in bile duct (IPNB) on baseline ultrasound and contrast-enhanced ultrasound (CEUS). Materials and Methods: The imaging features on baseline ultrasound and CEUS in 16 pathologically proven IPNB lesions in 15 patients were retrospectively analyzed. Real-time contrast specific modes and contrast agent of SonoVue were used for CEUS. Results: Bile duct dilation was present in all patients. The mean lengths for the intraductal papillary adenomas and adenocarcinomas were 2.5 ± 1.1 (range, 1.2 – 4.2 cm) and 5.6 ± 2.0 cm (range, 3.3 – 9.8 cm) (P = 0.004). Three imaging types of IPNB on ultrasound were depicted: bile duct dilation with intraductal mass (n = 8), bile duct dilation without intraductal mass (n = 3), and cystic-solid mixed type (n = 5). On CEUS, solid components of 13 lesions appeared hyper- (n = 12) or iso-enhancement (n = 1) in the arterial phase whereas all showed hypo-enhancement in the portal and late phases. For 3 lesions of bile duct dilation without intraductal mass, CEUS showed non-enhancement during all phases. Pre-surgical CEUS and conventional ultrasound made correct diagnoses in 12 (75.0 %) and 5(31.3 %) of 16 IPNBs respectively (P = 0.04). For CECT, correct diagnosis was also achieved in 12 (75.0 %) of 16 lesions (P = 1.00, in comparison with CEUS). Conclusions: IPNB should be taken into consideration when intraductal mass or cystic-solid mass with bile duct dilation, or remarkable bile duct dilation without intraductal mass, are found on US. Intraductal mass length > 3.0 cm is more commonly found in malignant IPNB. CEUS might facilitate the diagnosis of IPNB by easily excluding the possibility of commonly found sludge, nonshadowing stones, or blood clots.

Objectives- Acoustic radiation force impulse elastography is a newly developed ultrasound elasticity imaging technique that included both Virtual Touch tissue quantification and Virtual Touch tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA). This study aimed to evaluate the usefulness of VTI in differentiating malignant from benign thyroid nodules. Methods- This study included 192 consecutive patients with thyroid nodules (n = 219) who underwent surgery for compressive symptoms or suspicion of malignancy. Tissue stiffness on VTI elastography was scored from 1 (soft) to 6 (hard). The VTI scores between malignant and benign thyroid nodules were compared. The intraobserver and interobserver agreement for VTI elastography was also assessed. Results- On VTI elastography: score 1 was found in 84 nodules (all benign); score 2 in 37 nodules (3 papillary carcinomas and 34 benign nodules); score 3 in 25 nodules (1 medullary carcinoma, 6 papillary carcinomas, and 18 benign nodules); score 4 in 53 nodules (50 papillary carcinomas and 3 benign nodules); score 5 in 17 nodules (14 papillary carcinomas and 3 benign nodules); and score 6 in 3 nodules (all papillary carcinomas). A VTI elasticity score of 4 or greater was highly predictive of malignancy (P< .01), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.0% (67 of 77), 95.8% (136 of 142), 91.8% (67 of 73), 93.1% (136 of 146), and 92.7% (203 of 219), respectively. The κ values were 0.69 for intraobserver agreement and 0.85 for interobserver agreement. Conclusions- Virtual Touch tissue elasticity imaging has great potential as an adjunctive tool combined with conventional sonography for differential diagnosis between benign and malignant thyroid nodules.

Aim To evaluate the reliability of contrast-enhanced ultrasonography (CEUS) for the detection of renal microvascular blood perfusion in a type 2 diabetic Goto-Kakizaki (GK) rat model. Methods Male GK and Wistar rats at the age of 4, 12 and 20 weeks (n = 10, respectively) were used for the study. Real-time and haemodynamic imaging of the renal cortex was performed using CEUS with SonoVue. Outage time-intensity curves (TICs) were applied for the analysis of basic intensity, slope rates of the ascending (S1) and descending curves (S2), time to peak (TTP), half time of peak descending (HDT), peak intensity (PI), and total area under the curve (AUC). Immunohistochemical staining for endothelial cells (ECs) was performed using the CD34 monoclonal antibody for the quantification of microvessel density and distribution. Results Images of the renal cortex microvascular beds after injection of SonoVue in the rats were rapidly and clearly displayed, and it is easy to differentiate the enhanced and faded images of renal perfusion. The TICs of the GK rats were much wider than the controls; however, no significant changes in PI were found in all aged rats. Ultrasonographic quantitative analysis revealed a decrease in S1 and S2, and an increase in TTP, HDT and AUC in the 12- and 20-week-old GK rats compared with the controls (P

To evaluate whether parametric imaging with contrast-enhanced ultrasound (CEUS) is equal to experienced radiologists after review of CEUS in differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH).An image processing software was used to quantitatively analyze the CEUS clips of 30 HCCs (mean diameter, 3.4±0.9 cm; range, 1.8-5.0 cm) and 30 FNHs (mean diameter, 3.0±1.1 cm; range, 1.1-5.0 cm). Low mechanical index contrast specific imaging modes and contrast agent of SonoVue® were applied for CEUS. Fourteen HCCs were pathologically diagnosed and 16 were clinically diagnosed, whereas all the FNHs were confirmed by pathological examination. Quantitative parameters of HCC and FNH were compared. The diagnostic performance between parametric imaging and two experienced readers was compared using the receiver operating characteristic (ROC) curve analysis.On parametric imaging, the rise time, time to peak and mean transit time for HCC and FNH were 16.7±11.1 s vs. 21.9±9.0 s (P=0.052), 29.9±14.1 s vs. 33.2±11.1 s (P=0.322), 115.0±90.9 s vs. 271.5±147.6 s (P0.001), respectively. The ROC analysis showed that, for the differentiation between HCC and FNH, the cut-off point for mTT was 107.93 s with the Az value of 0.817 (95% CI: 0.703-0.931), and the Az value was 0.834 (95%CI: 0.728-0.941) for two experienced readers (P=0.417 compared with mTT). The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were 96.7%, 66.7%, 81.7%, 74.4%, and 95.2%, respectively, for parametric imaging, and 86.7%, 76.7%, 81.7%, 78.8%, and 85.2%, respectively, for two experienced readers (all P0.05 compared with parametric imaging).Parametric imaging with CEUS is helpful for characterization the typical dynamic effects of microvascularization of HCC and FHH and is equal to experienced readers in the differential diagnosis between HCC and FNH.

Primary hepatic angiosarcoma (PHA) is a rare malignancy with a badly poor prognosis. The extremely low morbidity and untypical clinical manifestations conduce to a missed diagnosis. The present study reported a case of an adult male patient who was pathologically confirmed to be PHA, which mimicked intrahepatic cholangiocarcinoma on conventional ultrasound and contrast-enhanced ultrasound. Findings on various imaging examinations were carefully evaluated and the associated literatures were also reviewed.