Abstract Background Accurate differentiation between benign and malignant adnexal masses is crucial for patients to avoid unnecessary surgic
Abstract Background Accurate differentiation between benign and malignant adnexal masses is crucial for patients to avoid unnecessary surgical interventions. Ultrasound (US) is the most widely utilized diagnostic and screening tool for gynecological diseases, with contrast-enhanced US (CEUS) offering enhanced diagnostic precision by clearly delineating blood flow within lesions. According to the Ovarian and Adnexal Reporting and Data System (O-RADS), masses classified as categories 4 and 5 carry the highest risk of malignancy. However, the diagnostic accuracy of US remains heavily reliant on the expertise and subjective interpretation of radiologists. Radiomics has demonstrated significant value in tumor differential diagnosis by extracting microscopic information imperceptible to the human eye. Despite this, no studies to date have explored the application of CEUS-based radiomics for differentiating adnexal masses. This study aims to develop and validate a multimodal US-based nomogram that integrates clinical variables, radiomics, and deep learning (DL) features to effectively distinguish adnexal masses classified as O-RADS 4–5. Methods From November 2020 to March 2024, we enrolled 340 patients who underwent two-dimensional US (2DUS) and CEUS and had masses categorized as O-RADS 4–5. These patients were randomly divided into a training cohort and a test cohort in a 7:3 ratio. Adnexal masses were manually segmented from 2DUS and CEUS images. Using machine learning (ML) and DL techniques, five models were developed and validated to differentiate adnexal masses. The diagnostic performance of these models was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, specificity, precision, and F1-score. Additionally, a nomogram was constructed to visualize outcome measures. Results The CEUS-based radiomics model outperformed the 2DUS model (AUC: 0.826 vs. 0.737). Similarly, the CEUS-based DL model surpassed the 2DUS model (AUC: 0.823 vs. 0.793). The ensemble model combining clinical variables, radiomics, and DL features achieved the highest AUC (0.929). Conclusions Our study confirms the effectiveness of CEUS-based radiomics for distinguishing adnexal masses with high accuracy and specificity using a multimodal US-based radiomics DL nomogram. This approach holds significant promise for improving the diagnostic precision of adnexal masses classified as O-RADS 4–5.