Contrast-enhanced Ultrasound Scoring Research Articles

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

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

Evaluating diagnostic significance: The utilization of elastography and contrast-enhanced ultrasound for differential diagnosis in breast lesions.

The primary aim of this study is to assess the diagnostic efficacy of elastography and contrast-enhanced ultrasound (CEUS) in the identification of breast lesions subsequent to the optimization and correction of the BI-RADS category 4 classification obtained through conventional ultrasound. The objective is to augment both the specificity and accuracy of breast lesion diagnosis, thereby establishing a reliable framework for reducing unnecessary biopsies in clinical settings. A cohort comprising 50 cases of breast lesions classified under BI-RADS category 4 was collected during the period from November 2022 and November 2023. These cases were examined utilizing strain elastography (SE), shear wave elastography (SWE), and CEUS. Novel scoring methodologies for ultrasonic elastography (UE) and CEUS were formulated for this investigation. Subsequently, the developed UE and CEUS scoring systems were used to refine and optimize the conventional BI-RADS classification, either in isolation or in conjunction. Based on the revised classification, the benign group was classified as category 3 and the suspected malignant group was classified as category 4a and above, with pathological results serving as the definitive reference standard. The diagnostic efficacy of the optimized UE and CEUS, both independently and in combination, was meticulously scrutinized and compared using receiver operating characteristic (ROC) curve analysis, with pathological findings as the reference standard. Within the study group, malignancy manifested in 11 cases. Prior to the implementation of the optimization criteria, 78% (39 out of 50) of patients underwent biopsies deemed unnecessary. Following the application of optimization criteria, specifically a threshold of≥8.5 points for the UE scoring method and≥6.5 points for the CEUS scoring method, the incidence of unnecessary biopsies diminished significantly. Reduction rates were observed at 53.8% (21 out of 39) with the UE protocol, 56.4% (22 out of 39) with the CEUS protocol, and 89.7% (35 out of 39) with the combined UE and CEUS optimization protocols. The diagnostic efficacy of conventional ultrasound BI-RADS category 4 classification for breast lesions is enhanced following optimized correction using UE and CEUS, either independently or in conjunction. The application of the combined protocol demonstrates a notable reduction in the incidence of unnecessary biopsies.

Diagnostic value of contrast-enhanced ultrasound in the activity of idiopathic retroperitoneal fibrosis: a retrospective study.

To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) in the disease activity of idiopathic retroperitoneal fibrosis (IRPF). This retrospective study included 148 CEUS examinations from 63 patients with IRPF treated in our hospital from April 2016 to September 2021. They were divided into two groups: IRPF active group (69 examinations) and inactive group (79 examinations). Uni- and multivariable analyses were used to identify independent risk factors for IRPF activity. Receiver operating characteristic (ROC) curves were drawn to establish different diagnostic models to evaluate the diagnostic value of IRPF activity. The z test was used to compare the differences of the area under the curves (AUCs). The value of CEUS in evaluating the variation of disease activity over time was also investigated between repeat patient studies. Univariate and multivariate logistic regression analyses revealed the thickness [odds ratio (OR) = 14.125, 95% confidence interval (CI) = 3.017-66.123] was the most significant independent risk factor for IRPF activity (P < 0.01). The best diagnostic model was model 3, which was established by CEUS score combined with thickness. The AUC was 0.944 (95%CI = 0.912-0.977), and the sensitivity and specificity were 89.86% and 86.08%, respectively. The diagnostic performance was not significantly improved after combining clinical symptom (back pain) and laboratory indicators [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]. Compared with before treatment, the CEUS score and thickness were significantly decreased after treatment (x2 = 14.580, P < 0.001 and z = 4.708, P < 0.001, respectively). CEUS has good diagnostic value for IRPF disease activity. Key points •Thickness and contrast-enhanced ultrasound score were significantly higher in the active group than those in inactive group (P < 0.001). •With thickness of 4 mm and contrast-enhanced ultrasound 2 score as optimal cut-off values, the sensitivity and specificity were 89.86%, 81.01% and 52.17%, 100.00%, respectively. •During follow-up, when the disease progressed, the change of CEUS score was earlier than the change of thickness.

Clinical application of super sensitive microflow ultrasound on the detection of intraplaque neovascularization in patients with atheromatous carotid artery plaque.

Contrast-enhanced ultrasound (CEUS) is a routine technique for detecting intraplaque neovascularization (IPN). However, the invasiveness and complexity of CEUS severely limit its clinical application. This article aims to investigate the application value of AngioPLUS (AP) technique in assessing IPN formation in patients with atheromatous (AS) carotid artery plaque. Patients diagnosed with carotid artery atherosclerosis combined plaque formation were recruited and their demographic characteristics including serum fasting blood glucose (FBG), triglyceride (TG), and low-density lipoprotein (LDL) were collected. AP was used to scoring intraplaque microvascular flow (IMVF), measuring the thickness and length of the plaque and determining the number of IPN of the plaque. IMVF score evaluated by AP was positively correlated with plaque length, thickness, IPN number, serum TG, LDL and FBG levels in patients with carotid atherosclerosis with plaque. The evaluation results of CEUS score and IMVF classification detected by AP of plaques were consistent in patients with carotid atherosclerosis. IMVF scoring by AP is a promising approach to assess IPN and plaque status in patients with atheromatous carotid artery plaque.

Clinical Application of C-TIRADS Category and Contrast-Enhanced Ultrasound in Differential Diagnosis of Solid Thyroid Nodules Measuring ≥1 cm.

BackgroundThe aim of this study was to investigate the performance of Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) category combined with contrast-enhanced ultrasound (CEUS) in diagnosing thyroid cancer.Material/MethodsFrom October 2020 to March 2021, 116 thyroid nodules from 113 patients who underwent conventional ultrasound and CEUS examinations at the General Hospital of Northern Theater Command were reviewed. In the conventional ultrasound examination, thyroid nodules were categorized by C-TIRADS. The nodules were reclassified based on CEUS scoring, then a combined diagnosis was made. The pathological results were taken as the criterion standard. To compare the diagnostic performance of the 3 methods according to the receiver operating characteristic curves produced for thyroid nodules.ResultsAfter chi-square test, the 7 characteristics of enhancement patterns, internal homogeneity, wash-in, wash-out, ring enhancement, morphology, and contrast agent retention characteristics (CAR) were statistically different between malignant and benign tumors; A high diagnostic performance was demonstrated by C-TIRADS combined with CEUS in diagnosing thyroid cancer. The area under the curve (AUC), the sensitivity, and the specificity of C-TIRADS combined with CEUS for diagnosing thyroid cancer were 0.918 (95% CI: 0.852–0.961), 80.9% (95% CI: 69.1–89.8%), and 90.6% (95% CI: 79.3–96.9%), respectively. The AUC of C-TIRADS alone was significantly lower than that of C-TIRADS combined with CEUS (P=0.0056), while there was no significant difference between CEUS and C-TIRADS combined with CEUS (P=0.59).ConclusionsThe combined method of C-TIRADS and CEUS, with reduced rate of thyroid nodule biopsy and clinical application value, has higher diagnostic accuracy than the single diagnosis method.

The Value of IOTA Simple Rules Combined With CEUS Scoring System in the Diagnosis of Benign and Malignant Ovarian Masses and Its Correlation With MVD and VEGF: A Preliminary Study.

To investigate the diagnostic value of International Ovarian Tumor Analysis (IOTA) simple rules combined with contrast-enhanced ultrasound (CEUS) scoring system in the differential diagnosis of ovarian tumors, and the correlations of the scoring system with microvessel density (MVD) and vascular endothelial growth factor (VEGF). One hundred eighty-nine patients with ovarian tumors were examined by routine ultrasound and CEUS. The enhanced characteristics of CEUS were observed, and the masses were classified by IOTA simple rules. To compare the diagnostic value of IOTA simple rules combined with CEUS scoring system and IOTA simple rules in the diagnosis of ovarian tumors. Immunohistochemistry was used to detect the expression of MVD and VEGF in postoperative tissue samples. The correlations between the new scoring system with MVD and VEGF were analyzed. The sensitivity (93.98%), specificity (94.34%), positive predictive value (92.86%), negative predictive value (95.24%), and accuracy (94.18%) of IOTA simple rules combined with CEUS scoring system in the diagnosis of ovarian tumors were higher than those of IOTA simple rules alone (all P < .05). The score system was significantly positively correlated with MVD and VEGF, and the r values were 0.77 and 0.63, respectively (P < .001). IOTA simple rules combined with CEUS scoring system was helpful to improve the accuracy of ultrasound diagnosis of ovarian tumors, which was significantly correlated with MVD and VEGF. It could provide important reference information for treatment scheme formulation and prognosis evaluation.

Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia.

Contrast-enhanced ultrasound (CEUS) is advantageous for evaluating microcirculation, and has been applied to assess arthritis in previous studies. However, CEUS examinations have not been studied for hemophilia arthritis. Hemophilia arthritis is different from other arthritis, because it is induced by spontaneous joint bleeding. Hence, CEUS may have special value in evaluating hemophilia arthritis. The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients. From August 2016 to January 2017, 81 severe hemophilia A patients, who were referred to our hospital for ultrasound joint assessment with conventional ultrasound, were enrolled. Among these 81 patients, 46 patients consented for CEUS examinations on the same day. Compared to color Doppler flow imaging (CDFI), four more joints presented with a blood flow signal under CEUS mode. In addition, the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound. The ultrasound scores (including the total grey-scale ultrasound score, joint effusion/hemarthrosis, synovial hypertrophy, CDFI semi-quantitative score, and CEUS semi-quantitative score) were significantly higher in the joint bleeding group than in the no joint bleeding group (P<0.05). Furthermore, these ultrasound scores were positively correlated with the joint bleeding frequency, and had the highest correlation with the CEUS score (r=0.620, P<0.05). CEUS can more accurately assess the degree of synovial hypertrophy and vascularization, and diagnose synovitis, when compared to conventional ultrasound. In addition, CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding, and providing more reliable evidence for individualized treatment.

The value of clinical-ultrasonographic feature model to predict the severity of secondary hyperparathyroidism

Objectives To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. Methods From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 μmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH <800 ng/L) and the severe SHPT group (sSHPT, iPTH ≥ 800 ng/L) according to the serum iPTH level. The clinical test data of patients were collected and CUS and CEUS examinations were performed for every patient. Multivariable logistic regression model according to clinical-ultrasonographic features was adopted to establish a nomogram. We performed K-fold cross-validation on this nomogram model and nomogram performance was determined by its discrimination, calibration, and clinical usefulness. Results There were 19 patients in the mSHPT group and 40 patients in the sSHPT group. Multivariable logistic regression indicated serum calcium, serum phosphorus and total volume of PTGs were independent predictors related with serum iPTH level. Even though CEUS score of wash-in and wash-out were showed related to severity of SHPT in univariate logistic regression analysis, they were not predictors of SHPT severity (p = 0.539, 0.474 respectively). The nomogram developed by clinical and ultrasonographic features showed good calibration and discrimination. The accuracy and the area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 0.888, 92.5%, 63.2% and 83.1%, respectively. When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the cohort (mean AUC = 0.833). Conclusions The clinical-ultrasonographic features model has good performance for predicting the severity of SHPT.

CEUS detection of biliary ischaemia during the first 4 weeks after liver transplantation predicts non-anastomotic biliary stricture

Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P < 0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P < 0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.

The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules.

To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P < .001), respectively. The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.

Cardiac thrombotic stability determined by contrast-enhanced echocardiography: investigative protocol and preliminary results

ObjectiveThis study’s intent was to test a new system for scoring cardiac thrombotic stability, based on contrast-enhanced ultrasound (CEUS).MethodsWe used human whole blood for an in vitro thrombotic model involving 1-h (T1h) and 7-day (T7d) subsets. The T1h group was monitored for 1 h continuously to observe for the formation of a new thrombus on the original thrombus base. Changes in thrombotic CEUS images, histologic features, and shear wave elastography were recorded over time. We also studied 28 patients diagnosed with cardiac thrombi, each examined by transthoracic echocardiography and CEUS.Thrombi were scored for substrate (Ts) and hardness (Th) based on the visualized degree of contrast penetration into the thrombi. Statistical analyses of Ts and Th reflected thrombolytic time and risk of embolism to other organs.ResultsHistologically, the loosely constructed ends of in vitro thrombi solidified over time. In addition, the average Young’s modulus of thrombi over time indicated a progressive increase in hardness. Contrast-enhancing agents were able to penetrate fresh, loose thrombi only, not chronic, stable thrombi. As Ts and Th increased, prolonged thrombolytic time and greater risk of embolism to other organs were apparent.ConclusionsOur data suggest that this new CEUS scoring system correlates well with cardiac thrombotic hardness and the quality of its underlying substrate, serving to quantify thrombotic stability.

Contrast-Enhanced Ultrasound for Biliary Ischemia: A Possible New Clinical Indication.

Biliary perfusion is considered to contribute to biliary diseases, but routine imaging methods are insufficient to show it. This research investigated the ability of contrast-enhanced ultrasound (CEUS) for biliary perfusion in a biliary ischemia model. This research consisted of 2 parts. First, to determine whether CEUS enhancement of the tiny biliary wall represents biliary perfusion, a vascular tracer was used as a reference to evaluate the consistency with the enhancement of the biliary wall on CEUS and the staining by the vascular tracer under the conditions of occluded and recovered biliary perfusion. In the second part, the ability of CEUS for biliary ischemia was further evaluated with microvascular density measurement as a reference. The enhancement patterns were assigned CEUS scores, in which higher scores meant more decreased enhancement, and the diagnostic ability of CEUS was assessed by a receiver operating characteristic curve analysis. The biliary wall was unstained by the vascular tracer and nonenhanced on CEUS when biliary perfusion was interrupted and was stained blue and enhanced after recovery. The biliary wall in the ischemia surgery group showed lower microvascular density measurements (P < .001), decreased enhancement levels (P < .001), and higher CEUS scores (P < .001). When a CEUS score of 3 or higher (obvious decrease of the biliary wall to hypoenhancement or nonenhancement in the arterial phase or rapid wash-out to nonenhancement in the portal venous phase) was applied, CEUS had sensitivity of 87.8%, specificity of 98.3%, accuracy of 93.8%, and an area under the receiver operating characteristic curve of 0.98. Contrast enhancement of the biliary wall on CEUS represents biliary perfusion and has reasonably good diagnostic performance for biliary ischemia in an experimental animal setting.

Diagnostic Efficiency of Gynecologic Imaging Reporting and Data System Combined With 3-dimensional Contrast-enhanced Ultrasound Scoring System in Evaluating Ovarian Tumor.

To estimate the value of gynecologic imaging reporting and data system (GI-RADS) combined with 3-dimensional contrast-enhanced ultrasound (3D-CEUS) scoring system in the differential diagnosis of ovarian tumor. Both of 2-dimensional ultrasound (2D-US) and 3D-CEUS were performed on 114 patients with ovarian masses by Voluson E8 with SonoVue (Bracco, Italy). Besides, dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) (Siemens Magneton Verio 3.0T, Germany) was performed on the patients. There were totally 62 benign and 52 malignant ovarian tumors in all patients. The ability of GI-RADS combined with 3D-CEUS scoring system to distinguish benign and malignant ovarian tumors was superior to conventional ultrasound GI-RADS classification. The sensitivity, specificity, and accuracy of GI-RADS combined with 3D-CEUS scoring system were 96.2% and 98.1%, 87.10%, whereas those of MRI were 87.10%, 91.23%, and 92.11% respectively, indicating that there was high concordance in ovarian tumors assessment between the 2 diagnostic methods. The new scoring system has a good correlation with microvessel density (P = 0.000, r = 0.73), estrogen receptor (P = 0.000, r = 0.59), progesterone receptor (P = 0.000, r = 0.56), and matrix metalloproteinase-9 (P = 0.000, r = 0.61). The GI-RADS combined with 3D-CEUS scoring system was valuable in clinical diagnosis and differential diagnosis of ovarian tumor and show good agreement with MRI.

Value of contrast-enhanced ultrasound in the diagnosis of breast US-BI-RADS 3 and 4 lesions with calcifications

To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for Breast Imaging-Reporting and Data System for Ultrasound (US-BI-RADS) 3 and 4 lesions with calcifications. A retrospective study of 168 breast lesions with calcifications detected on both mammography and conventional ultrasonography (US) in 152 patients were categorised as US-BI-RADS 3-4 at US between June 2009 and June 2018. CEUS scores were obtained based on a CEUS five-point scoring system. The combination of US-BI-RADS and CEUS scores created the Rerated BI-RADS (referred to as CEUS-BI-RADS). All results were compared with the histological findings. The diagnostic performances of US and CEUS-BI-RADS were compared. The diagnostic sensitivity, specificity, and accuracy of US were 81.8% (95% confidence interval [CI]: 71.6%, 92%), 85% (95% CI: 78.4%, 91.5%), and 83.9% (95% CI: 78.4%, 89.5%), respectively, while those for CEUS-BI-RADS were 98.2% (95% CI: 94.7%, 100%), 90.3% (95% CI: 84.8%, 95.7%), and 92.9% (95% CI: 89%, 96.8%), respectively. The diagnostic sensitivity and accuracy values of CEUS-BI-RADS greatly improved compared with those of US (p=0.003 and p=0.004, respectively). The areas under the receiver operating characteristic (ROC) curves for US and CEUS-BI-RADS were 0.888 (95% CI: 0.840, 0.936) and 0.963 (95% CI: 0.936, 0.989), respectively. The diagnostic efficacy of CEUS-BI-RADS was significantly higher than that of US alone (p=0.004). CEUS-BI-RADS significantly improves the diagnostic accuracy for breast US-BI-RADS 3 and 4 lesions with calcifications compared with US.

A Prospective Validation Cohort Study of a Prediction Model on Non-sentinel Lymph Node Involvement in Early Breast Cancer.

Early breast cancer with one or two sentinel lymph nodes (SLNs) may omit axillary lymph node dissection (ALND) if followed by radiotherapy. However, only less than one-third of the patients have positive non-SLNs and can truly benefit from radiotherapy. Before any regional treatment decision, the risk of non-SLN metastasis must be identified. The authors previously developed a predictive model for non-SLN involvement using CK19 mRNA and contrast-enhanced ultrasound (CEUS) score in a training set. They designed a further study to evaluate the predictive effect using the model prospectively in a validation set of one or two involved SLNs. This study identified early breast cancer patients at Zhejiang Cancer Hospital from July 2017 to June 2018. The CK19 mRNA tested by quantitative real-time polymerase chain reaction and CEUS scores were collected before surgery. Patients with one or two involved SLNs were enrolled and underwent ALND. The estimated percentage of non-SLN involvement was calculated by the authors' model formula and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. The false-negative rates, predictive accuracy, and area under curve (AUC) were compared between two predictive models. The study enrolled 235 patients, and 35.36% (83/235) of them had non-SLN involvement. The authors' model had a false-negative rate of 6% and an accuracy of 94.9%. The AUC was 0.952 (95% confidence interval [CI] 0.922-0.982), which was significantly higher than that of the MSKCC model at all three cutoff value levels. The authors' model, using CK19 mRNA and the CEUS score, showed the potential predictive value of non-SLNs before surgery for early breast cancer patients. NCT02992067, NCT03280134.

The clinical role of contrast enhanced ultrasound in differential diagnosis of BI-RADS 4 breast disease.

To clarify the clinical role of contrast enhanced ultrasound (CEUS) in predicting BI-RADS 4 breast disease. A total of 92 sites of BI-RADS 4 breast diseases were reassessed by routine ultrasound and CEUS. The main indicators of routine ultrasound, CEUS and the combination of the two modalities were picked up by binary logistic regression analysis, scoring 0 for benign and 1 for malignant characteristics with pathology as referential standard to generate corresponding score systems of them. Finally, the receiver operating characteristic curves (ROC) were applied to compare the diagnostic efficacy of the three score systems. As pathological results showing, there were 43 malignant and 49 benign sites in total. Binary logistic regression analysis indicated that the margin, micro-calcification, and hyperechoic halo were main indicators for routine ultrasound score system. The scope expansion and pathological vessels in CEUS were main indicators for CEUS score system. The microcalcification, hyperechoic halo, the scope expansion and pathological vessels in CEUS were main indicators for the combination score system of the two modalities. The sensitivity, specificity and the area under ROC curve (AUC) of routine US, CEUS and the combination of the two modalities score systems were 74.4%, 91.8%, 0.885 and 88.4%, 87.8%, 0.901 and 86.0%, 95.9%, 0.937, respectively. In summary, CEUS is helpful for us to identify malignant disease and plays a supplementary role in predicting BI-RADS 4 breast disease in some extent. The scope expansion and pathological vessels in CEUS may be the most useful indicators.

A prospective validation cohort study of a prediction model on non-sentinel lymph node involvement in early breast cancer.

559 Background: Early breast cancer (cT1-2N0) with one or two sentinel lymph node (SLN) involved may avoid axillary lymph node dissection (ALND) if follow by radiotherapy supported by Z0011 and AMAROS trials. However, only less than one-third of those patients have positive non-sentinel lymph node (nSLN) and can truly benefit from radiotherapy or ALND in those two trials. It is necessary to identify the risk of nSLN metastasis before local treatment decision. We previously developed a predictive model for nSLN involvement using circulating CK19 mRNA level combined with contrast-enhanced ultrasound (CEUS) score (ASCO2017 poster 239, NCT02992067) in a training set. To evaluate the predict effect of this model, we designed a further study using the model prospectively in a validation set (NCT03280134). Methods: We identified early breast cancer cases in Zhejiang Cancer Hospital from July 2017 to June 2018. The level of circulating CK19 mRNA tested by qRT-PCR and CEUS scores were collected before surgery in each case. Patients with 1~2 SLN involved were enrolled and continued for ALND. The estimated percentage of nSLN-involved were calculated both by our model formula and the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. The predictive accuracy and false negative rates (FNR) were evaluated and the area under curve (AUC) was compared between two predictive models. Results: Totally, 235 patients diagnosed as early breast cancer with 1~2 SLN involved were enrolled and 35.36% of them were nSLN involved after ALND. The total accuracy and FNR by our model for nSLN-involved prediction was 94.89% and 6.02%, respectively. The AUC was 0.952 (95%CI, 0.922~0.982), significantly higher than that in MSKCC model 0.880 (95%CI, 0.833~0.927). Furthermore, only CK19 mRNA level (HR = 40.091, 95%CI, 13.663~117.635) and CEUS score (HR = 2.009, 95%CI 1.158~3.485) are significantly related to nSLN involvement in both univariate and multivariate analysis, adjusted by age, menopause statue, tumor size, histological grade, estrogen receptor, progesterone receptor and human epidermalgrowth factor receptor-2 expression. Conclusions: Our model using CK19 mRNA and CEUS score showed potential predictive value of nSLN before surgery in early breast cancer patients. Further validation in larger multicenter cohort is warranted before changing clinical practice.

The value of combined scoring of contrast-enhanced ultrasound and ultrasonic elastography in the differential diagnosis of TI-RADS 4 nodules

Objective To evaluate the diagnostic value of combined scoring of contrast-enhanced ultrasound(CEUS) and ultrasonic elastography(UE) for thyroid imaging reporting and date system(TI-RADS) 4 type nodules. Methods The CEUS and UE features of 520 TI-RADS 4 type nodules were analyzed retrospectively.The scores of each nodule were evaluated and compared with pathological results and fine-needle aspiration cytology(FNAC). ROC curve was used to compare the diagnostic value of CEUS combined with UE or alone in the differential diagnosis of TI-RADS 4 nodules. Results The sensitivity, specificity, accuracy and area under the curve(AUC) of UE were 82.34%, 82.25%, 82.31% and 0.841, respectively, when the cut-off value of UE score was 4. The sensitivity, specificity, accuracy and AUC of CEUS were 78.63%, 65.68%, 74.42% and 0.750, respectively, when the cut-off value of CEUS score was 4. The sensitivity, specificity, accuracy and AUC of CEUS combined with UE were 92.31%, 75.74%, 86.92% and 0.885, respectively, when the cut-off value of combined score was 6. The sensitivity and accuracy of combined score were higher than those of two other methods, the difference was statistically significant (all P<0.05), the AUC of combined score was the biggest, it had the highest diagnostic efficacy. Conclusions Combined scoring of CEUS and UE can improve the accuracy in the differential diagnosis of TI-RADS 4 type nodules. Key words: Contrast-enhanced ultrasound; Ultrasonic elastography; Thyroid neoplasms; Thyroid Imaging Reporting and Date System

CK19 combined with contrast-enhanced ultrasound: A prediction model for non-sentinel lymph node involvement in early breast cancer.

11539 Background: According to Z0011 and AMAROS trials, patients with breast cancer stage cT1~2cN0 and sentinel lymphnode (SLN) 1~2 involvement can avoid axillary lymphnode dissection (ALND). But the risk of non-sentinel lymphnode (nSLN) involvement in those early stage patients is still unclear and it is difficult to predicting the risk before surgery. Our previous study showed CK19 mRNA in peripheral blood had predicative value of nSLN involvement. Also, contrast-enhanced ultrasound (CEUS) is a new effective method exmaming axillary lymph node. We aim to establish a prediction model for nSLN involvement in early breast cancer using CK19 combined with CEUS score. Methods: We identified 119 cases diagnosed early breast cancer (stage cT1~2cN0 and 1~2 SLNs involvement as in Z0011 and AMAROS trials) from Oct 2015 to Nov 2016 in Zhejiang Cancer Hospital. The CK19 mRNA of peripheral blood by RT-PCR and CEUS score of axillary lymph nodes were acquired before surgery. We used logistic regression analysis for filtering out valuable predictive clinical parameters and establishing formulas to calculate the probability of nSLN involvement. Our model was compared with Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, which is one of the most reliable and validated methods for predicting of nSLN. Results: The histological grade, CK19 and CEUS score were screened by logistic regression analysis into the formula to calculate the probability of nSLN involvement. The sensitivity, specificity, total accuracy of this model was 89.13%, 80.82% and 84.03%, respectively. The false negative rate was 10.87%. The model had high quality of consistency (Kappa 0.675, p &lt; 0.01) and goodness of fit (likelihood-ratio test, -2log liklihood = 84.607). The area under curve (AUC) of ROC was significantly higher (P &lt; 0.01) in our model (0.914, 95%CI, 0.863~0.965) than in MSKCC nomogram (0.563, 95%CI, 0.459~0.667). Conclusions: The prediction model based on CK19 and CEUS score has satisfying sensitivity, specificity and accuracy, more effective than MSKCC nomogram. It is a valuable model of evaluating the risk of nSLN involvement in early breast cancer before surgery, picking out the patients who can truly avoid ALND.

Incorporating Contrast-Enhanced Ultrasound into the BI-RADS Scoring System Improves Accuracy in Breast Tumor Diagnosis: A Preliminary Study in China

The aim of the study was to develop a scoring model incorporating the Breast Imaging Reporting and Data System (BI-RADS) and the contrast-enhanced ultrasound (CEUS) scoring system to differentiate between malignant and benign breast lesions. A total of 524 solid breast masses in 490 consecutive patients were evaluated with conventional US and CEUS in this prospective study. Each lesion was scored according to BI-RADS, CEUS, and CEUS-rerated BI-RADS. The diagnostic specificity, sensitivity and accuracy of BI-RADS were 77.9%, 88.9% and 84.0%, respectively, and the area under the receiver operating characteristic curve was 0.834. The corresponding values for rerated BI-RADS were 82.1%, 96.9%, 90.3% and 0.895. The area under the receiver operating characteristic curve of BI-RADS alone was significantly smaller than that of CEUS and the rerated BI-RADS (p = 0.008 compared with CEUS, p = 0.002 compared with rerated BI-RADS). This study indicates that rerating BI-RADS with the CEUS scoring system improves its diagnostic accuracy.