SPACE: Subregion Perfusion Analysis for Comprehensive Evaluation of Breast Tumor Using Contrast-Enhanced Ultrasound-A Retrospective and Prospective Multicenter Cohort Study.

Objective: To develop a dynamic contrast-enhanced ultrasound (CEUS)-based method for segmenting tumor perfusion subregions, quantifying tumor heterogeneity, and constructing models for distinguishing benign from malignant breast tumors.

Methods: This retrospective-prospective cohort study analyzed CEUS videos of patients with breast tumors from four academic medical centers between September 2015 and October 2024. Pixel-based time-intensity curve (TIC) perfusion variables were extracted, followed by the generation of perfusion heterogeneity maps through cluster analysis. A combined diagnostic model incorporating clinical variables, subregion percentages, and radiomics scores was developed, and subsequently, a nomogram based on this model was constructed for clinical application.

Results: A total of 339 participants were included in this bidirectional study. Retrospective data included 233 tumors divided into training and test sets. The prospective data comprised 106 tumors as an independent test set. Subregion analysis revealed Subregion 2 dominated benign tumors, while Subregion 3 was prevalent in malignant tumors. Among 59 machine-learning models, Elastic Net (ENET) (α = 0.7) performed best. Age and subregion radiomics scores were independent risk factors. The combined model achieved area under the curve (AUC) values of 0.93, 0.82, and 0.90 in the training, retrospective, and prospective test sets, respectively.

Conclusion: The proposed CEUS-based method enhances visualization and quantification of tumor perfusion dynamics, significantly improving the diagnostic accuracy for breast tumors.