A conditional inference tree model for predicting cancer risk of non-mass lesions detected on breast ultrasound.

OBJECTIVES: To generate and validate a prediction model based on imaging features for cancer risk of non-mass lesions (NMLs) detected on breast ultrasound (US). METHODS: In this single-center study, consecutive women with 503 NMLs detected on breast US between 2012 and 2019 were retrospectively identified. The lesions were randomly assigned to the training or testing dataset with a 70/30 split. Age, symptoms, lesion size, and US features were collected. Multivariate analyses were employed to identify risk factors associated with malignancy. The predictive model was developed by using conditional inference trees (CTREE). RESULTS: There were 498 patients (50.9 ± 13.29 years; range, 22-88 years) with 503 NMLs with histopathologic results or > 2-year follow-up, including 224 (44.5%) benign and 279 (55.5%) malignant lesions. At multivariate analysis, age (odds ratio (OR) = 1.08, 95% confidence interval (CI), 1.06-1.11, p < 0.001), NMLs with focal mass effect (OR = 3.03, 95% CI, 1.59-5.81, p = 0.001), indistinct glandular-fat interface (GFI) (OR = 4.23, 95% CI, 2.31-7.73, p < 0.001), geographic (OR = 3.47, 95% CI, 1.20-10.8, p = 0.022) and mottled (OR = 3.67, 95% CI, 1.32-10.21, p = 0.013) patterns, and calcifications (OR = 2.15, 95% CI, 1.16-4.01, p = 0.016) were associated with malignancy. The GFI status, architectural patterns, general morphology, and calcifications were consistently identified as the strongest US predictors of malignancy using CTREE analysis. Based on these factors, individuals were stratified into six risk groups. The predictive model showed an area under the curve of 0.797 in the testing dataset. CONCLUSION: The CTREE model efficiently aids in interpreting and managing ultrasound-detected breast NMLs, overcoming BI-RADS limitations by refining cancer risk stratification. CLINICAL RELEVANCE STATEMENT: The CTREE model allows for the reclassification of BI-RADS categories into subgroups with varying malignancy probabilities, thus providing a valuable enhancement to the BI-RADS assessment for the diagnosis of ultrasound-detected NMLs, with the potential to minimize unnecessary biopsies. KEY POINTS: • The indistinct glandular-fat interface (GFI) status, NML with focal mass effect, geographic or mottled patterns, and calcifications are the strongest imaging predictors of malignant non-mass lesions (NMLs) detected on breast US. • A practical system has been created to categorize NMLs found in breast US; each classification is associated with a degree of diagnostic certainty. • The model may contribute to patient stratification by determining the relative likelihood of malignancy and thus support clinical decision-making and evidence-based management.

Ultrasound-based radiomics analysis for preoperative prediction of central and lateral cervical lymph node metastasis in papillary thyroid carcinoma: a multi-institutional study.

BACKGROUND: An accurate preoperative assessment of cervical lymph node metastasis (LNM) is important for choosing an optimal therapeutic strategy for papillary thyroid carcinoma (PTC) patients. This study aimed to develop and validate two ultrasound (US) nomograms for the individual prediction of central and lateral compartment LNM in patients with PTC. METHODS: A total of 720 PTC patients from 3 institutions were enrolled in this study. They were categorized into a primary cohort, an internal validation, and two external validation cohorts. Radiomics features were extracted from conventional US images. LASSO regression was used to select optimized features to construct the radiomics signature. Two nomograms integrating independent clinical variables and radiomics signature were established with multivariate logistic regression. The performance of the nomograms was assessed with regard to discrimination, calibration, and clinical usefulness. RESULTS: The radiomics scores were significantly higher in patients with central/lateral LNM. A radiomics nomogram indicated good discrimination for central compartment LNM, with an area under the curve (AUC) of 0.875 in the training set, the corresponding value in the validation sets were 0.856, 0.870 and 0.870, respectively. Another nomogram for predicting lateral LNM also demonstrated good performance with an AUC of 0.938 and 0.905 in the training and internal validation cohorts, respectively. The AUC for the two external validation cohorts were 0.881 and 0.903, respectively. The clinical utility of the nomograms was confirmed by the decision curve analysis. CONCLUSION: The nomograms proposed here have favorable performance for preoperatively predicting cervical LNM, hold promise for optimizing the personalized treatment, and might greatly facilitate the decision-making in clinical practice.

Characterization of Early Hepatocellular Carcinoma and High-Grade Dysplastic Nodules on Contrast-Enhanced Ultrasound: Correlation With Histopathologic Findings.

OBJECTIVES: To explore the enhancement features of early hepatocellular carcinoma (HCC, including well-differentiated HCC and high-grade dysplastic nodules with a focus of HCC) and high-grade dysplastic nodules (HGDNs) on contrast-enhanced ultrasound (CEUS), correlated with the histopathologic findings. METHODS: This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings. RESULTS: Thirty-eight (55.1%) early HCCs showed arterial-phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late-phase wash-out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash-out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very-late wash-out (>120 seconds). Wash-out was not observed in all HGDNs. Of the 16 HGDNs, arterial-phase isoenhancement without portal venous/late-phase wash-out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial-phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039). CONCLUSIONS: Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

BACKGROUND: Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. METHODS: Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS: Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CONCLUSIONS: CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Papillary breast lesions on contrast-enhanced ultrasound: morphological enhancement patterns and diagnostic strategy.

OBJECTIVES: To identify features which determine the papillary nature of breast lesions by contrast-enhanced ultrasound (CEUS) based on morphological and pathological correlations, and predict which papillomas are malignant. METHODS: A retrospective review of 47 papillary lesions and 51 hypervascular benign abnormalities was performed. Enhancement patterns and diagnostic performance of CEUS were assessed. RESULTS: The most frequent finding in papillary lesions was perilesional linear ductal enhancement (87.2%) followed by heterogeneous enhancement (80.9%), and the presence of perfusion defects (66%). Among all CEUS morphological descriptors, a perilesional linear ductal enhancement pattern was the most effective feature to discriminate between papillary and hypervascular benign lesions. Using this criterion, the positive and negative predictive value for papilloma were 100% and 89.5%, respectively. A perilesional linear ductal pattern correlated with a ductal origin. The distinctive features associated with atypical or malignant papillomas were non-confluent enhancement, late overall wash-out, the presence of regional perfusion defect, clumped vascular pattern, and the presence of peripheral radial or penetrating vessels. The sensitivity, specificity, and positive and negative predictive values for predicting malignancy were 91.7%, 82.6%, 84.6% and 90.5%, respectively. CONCLUSIONS: CEUS provided characteristic enhancement patterns which could be helpful for identifying papillary lesions and for predicting potentially malignant papillomas. KEY POINTS: Papillary breast lesions display a characteristic appearance on CEUS. Adding CEUS to conventional US helps identify the papillary nature of papillomas. CEUS may be helpful for predicting potential malignancies among papillomas.

Quantitative analysis of pre-treatment dynamic contrast-enhanced ultrasound for assessing the response of colorectal liver metastases to chemotherapy plus targeted therapy: a dual-institutional study.

OBJECTIVES: To investigate the clinical value of pre-treatment quantitative contrast-enhanced ultrasound (CEUS) in assessing the response of colorectal liver metastases (CRLM) to chemotherapy plus targeted therapy. METHODS: This study retrospectively enrolled 50 CRLM patients from the Zhongshan Hospital, Fudan University as the training cohort and 14 patients from Shanghai Tenth People's Hospital as the testing cohort. Patients underwent the CEUS examination before receiving chemotherapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI) plus targeted therapy (Bevacizumab or Cetuximab). The therapy response was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 based on pre-treatment CT and 3-month follow-up CT after therapy. Dynamic analysis was performed by VueBox® software. Time-intensity curves with quantitative perfusion parameters were obtained. In the training cohort, univariable and multivariable logistic regression analyses were used to develop the predictive model of therapy response. The predictive performance of the developed model was validated in the testing cohort. RESULTS: After the logistic regression analyses, the peak enhancement (PE) (odds ratio = 1.640; 95% confidence intervals [CI] 1.022-2.633) and time to peak (TTP) (odds ratio = 0.495; 95% CI 0.246-0.996) were determined as independent predictive factors. PE and TTP generated from VueBox® were not affected by ultrasound instruments and contrast agent dosage in therapy response evaluation (P > 0.05). The logistic regression model achieved satisfactory prediction performance (area under the curve: 0.923 in the training cohort and 0.854 in the testing cohort). CONCLUSION: CEUS with dynamic quantitative perfusion analysis, which presents high consistency, has potential practical value in predicting the response of CRLM to chemotherapy plus targeted therapy.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

Response Evaluation Using Contrast-Enhanced Ultrasound for Unresectable Advanced Hepatocellular Carcinoma Treated With Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy.

OBJECTIVE: The aim of the work described here was to evaluate the role of contrast-enhanced ultrasound (CEUS) in response evaluation for unresectable advanced hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors (TKIs) plus anti-programmed cell death protein-1 (PD-1) antibody therapy. METHODS: A prospective cohort of consecutive patients with HCC who received combined TKI/anti-PD-1 antibody treatment for unresectable HCC between January 2022 and October 2022 was included in this study. The patients underwent unenhanced ultrasound (US) and CEUS examinations before treatment and at follow-up. Changes in the largest diameters of the target tumor on unenhanced US and the largest diameters of the enhancing target tumors on CEUS were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with unenhanced US and magnetic resonance imaging/computed tomography (MRI/CT) and modified RECIST (mRECIST) with CEUS and CEMRI/CT were used to assess treatment response. RESULTS: A total of 24 HCC patients (23 men and 1 woman; mean age: 56.5 ± 8.5 y; Barcelona Clinic Liver Cancer stage C, 62.5%; 29 intrahepatic target tumors) were studied. Calculations of degree of necrosis in the target tumors revealed no significant differences between CEUS and CEMRI/CT (44.5 ± 36.2% vs. 45.3 ± 36.8%, p = 0.862). As for the differentiation of responders from non-responders, the agreement between RECIST version 1.1 of unenhanced US and mRECIST-CEUS was poor (κ coefficient = 0.233). Meanwhile, there was a high degree of concordance between mRECIST-CEUS and mRECIST-CEMRI/CT (κ coefficient = 0.812). CONCLUSION: CEUS proved to be superior to baseline US and is comparable to CEMRI/CT in defining treatment outcome for combined TKI/anti-PD-1 antibody therapy.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

PURPOSE: To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). METHODS: This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. RESULT: We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. CONCLUSION: The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Littoral cell angioma of the spleen: sonographic-pathologic comparison.

OBJECTIVES: The purpose of this study was to evaluate the sonographic and pathologic features of littoral cell angioma of the spleen in 7 patients. METHODS: The sonographic appearance in 7 cases of littoral cell angioma confirmed by surgical pathologic examination was retrospectively reviewed. All underwent color Doppler imaging. Two underwent contrast-enhanced sonography. The sonographic appearance was compared with pathologic findings. RESULTS: Splenic lesions were solitary in 5 cases and multiple in 2 cases. The masses ranged from 10 to 64 mm in maximum diameter. Five hypoechoic and 2 hyperechoic lesions on grayscale sonography corresponded to few and multiple blood-filled spaces on pathologic examination, respectively. Four hypovascular lesions, 1 hypervascular lesion, and the other 2 hypervascular lesions full of color flow signals on color Doppler imaging corresponded to few, several, and multiple arteries on pathologic examination. On contrast-enhanced sonography, 1 hypervascular lesion full of color flow signals showed homogeneous hyperenhancement for 8 minutes during the arterial and parenchymal phases. One hypovascular lesion showed inhomogeneous isoenhancement transiently during the arterial phase and became hypoechoic later. CONCLUSIONS: Littoral cell angioma is a primary vascular splenic neoplasm with variable features on grayscale sonography and color Doppler imaging as well as contrast-enhanced sonography. The sonographic appearance of littoral cell angioma mainly depends on the type and number of tumor vessels.

Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer.

OBJECTIVES: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. METHODS: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. RESULTS: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n=128) were retraction phenomenon (odds ratio [OR]=10.188), post-acoustic shadowing (OR=5.112), and echogenic halo (OR=3.263, P<0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n=39) were calcifications (OR=6.210), absence of retraction phenomenon (OR=4.375), non-mass lesions (OR=4.286, P<0.001), absence of echogenic halo (OR=3.851, P=0.035), and post-acoustic enhancement (OR=3.641, P=0.008). The predictors for the Triple-Negative subtype (n=47) were absence of retraction phenomenon (OR=5.884), post-acoustic enhancement (OR=5.255, P<0.001), absence of echogenic halo (OR=4.138, P=0.002), and absence of calcifications (OR=3.363, P=0.001). Predictors for the Luminal-B subtype (n=89) had a relatively lower association (OR≤2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for the Luminal-A subtype (OR=9.063, P<0.001) when present and for the Triple-Negative subtype (OR=4.875, P<0.001) when absent. CONCLUSIONS: ABVS imaging features, especially retraction phenomenon, have a strong correlation with the molecular subtypes, expanding the scope of ultrasound in identifying breast cancer subtypes with confidence.

Comparison of retraction phenomenon and BI-RADS-US descriptors in differentiating benign and malignant breast masses using an automated breast volume scanner.

OBJECTIVE: To compare the diagnostic values of retraction phenomenon in the coronal planes and descriptors in the Breast Imaging Reporting and Data System-Ultrasound (BI-RADS-US) lexicon in differentiating benign and malignant breast masses using an automated breast volume scanner (ABVS). MATERIALS AND METHODS: Two hundred and eight female patients with 237 pathologically proven breast masses (120 benign and 117 malignant) were included in this study. ABVS was performed for each mass after preoperative localization by conventional ultrasonography (US). Multivariate logistic regression analysis was performed to assess independent variables for malignancy prediction. Diagnostic performance was evaluated through the receiver operating characteristic (ROC) curve analysis. RESULTS: Retraction phenomenon (odds ratio [OR]: 76.70; 95% confidence interval [CI]: 12.55, 468.70; P<0.001) was the strongest independent predictor for malignant masses, followed by microlobulated margins (OR: 55.87; 95% CI: 12.56, 248.44; P<0.001), angular margins (OR: 36.44; 95% CI: 4.55, 292.06; P=0.001), calcifications (OR: 5.53; 95% CI: 1.34, 22.88; P=0.018,) and patient age (OR: 1.10; 95% CI: 1.03, 1.17; P=0.004). Mass shape, orientation, echo pattern, indistinct margins, spiculated margins, and mass size were not significantly associated with breast malignancy. Area under the ROC curve (Az) for microlobulated margins and retraction phenomenon was higher than that for other significant independent predictors. Az, sensitivity, and specificity were 0.877 (95% CI: 0.829, 0.926) and 0.838 (95% CI: 0.783, 0.892), 82.9% and 70.1%, and 92.5% and 98.3%, respectively, for microlobulated margins and retraction phenomenon. CONCLUSIONS: Retraction phenomenon and microlobulated margins have high diagnostic values in the differentiation of benign and malignant breast masses using an ABVS.