A 2.5D multichannel deep learning model using contrast-enhanced ultrasound for predicting malignancy in breast nodules: a two-center study.

Objective: To evaluate a novel multichannel deep learning (DL) model using contrast-enhanced ultrasound (CEUS) data with multiple regions of interest (ROIs) and time-intensity curve (TIC)-derived key frames for predicting breast nodule malignancy. Clinical features were integrated into a combined model for robust, generalizable breast lesion classification. The model was further evaluated as an AI-assisted decision support tool through direct comparison with BI-RADS classification by senior radiologists. Methods: This retrospective two-center study enrolled 141 patients with breast nodules: 89 from Institution 1 (June 2016-October 2017; training cohort, n=62; internal validation, n=27) and 52 from Institution 2 (November 2022-November 2024; external validation). BI-RADS categories were extracted from original radiology reports and binarized at ≥4B for malignancy prediction. Tumors were segmented on B-mode and CEUS images to define intratumoral ROIs, tumor bounding boxes, and peritumoral expansions (2 mm and 5 mm). TIC phases (initial, ascending, peak, descending, wash-out) were stacked into multichannel 2.5-dimensional (2.5D) inputs. DenseNet201 models, pretrained on ImageNet, were trained for 2D and 2.5D DL across ROI types. Outputs from the clinical model and optimal intratumoral plus 2-mm peritumoral ROI models were fused via logistic regression. Performance was evaluated using area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow calibration, decision curve analysis (DCA).and DeLong test for comparison with BI-RADS. Results: Among 2.5D models, the multichannel variant with intratumoral plus 2-mm peritumoral ROI showed highest external validation performance. The combined model, constructed by fusing the output of the optimal MultiChannel_2.5D_DL architecture (intratumoral + 2-mm peritumoral ROI) with the 2D_DL and clinical models via logistic regression, outperformed individual models externally (AUC 0.949 [95% CI: 0.888, 1.000] vs. clinical AUC 0.821 [95% CI: 0.671, 0.970], p=0.04; vs. 2D AUC 0.789 [95% CI: 0.660, 0.918], p=0.01; vs. 2.5D AUC 0.824 [95% CI: 0.677, 0.972], p=0.03). In direct comparison in the external validation cohort, the combined model demonstrated diagnostic performance comparable to that of senior radiologists (AUC 0.949 [95% CI: 0.888, 1.000] vs. 0.897 [95% CI: 0.808, 0.986], p=0.15). Conclusion: This combined model, integrating the optimal MultiChannel_2.5D_DL output with 2D_DL and clinical features, offers promising accuracy and generalizability as a decision support tool for CEUS-based breast nodule malignancy prediction, potentially assisting radiologists in reducing interobserver variability and unnecessary biopsies.