Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study

Background: There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach. Methods: In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model. Results: Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901–1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors. Conclusions: The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.