Dual-energy three-compartment breast imaging for compositional biomarkers to improve detection of malignant lesions.

Background: While breast imaging such as full-field digital mammography and digital breast tomosynthesis have helped to reduced breast cancer mortality, issues with low specificity exist resulting in unnecessary biopsies. The fundamental information used in diagnostic decisions are primarily based in lesion morphology. We explore a dual-energy compositional breast imaging technique known as three-compartment breast (3CB) to show how the addition of compositional information improves malignancy detection. Methods: Women who presented with Breast Imaging-Reporting and Data System (BI-RADS) diagnostic categories 4 or 5 and who were scheduled for breast biopsies were consecutively recruited for both standard mammography and 3CB imaging. Computer-aided detection (CAD) software was used to assign a morphology-based prediction of malignancy for all biopsied lesions. Compositional signatures for all lesions were calculated using 3CB imaging and a neural network evaluated CAD predictions with composition to predict a new probability of malignancy. CAD and neural network predictions were compared to the biopsy pathology. Results: The addition of 3CB compositional information to CAD improves malignancy predictions resulting in an area under the receiver operating characteristic curve (AUC) of 0.81 (confidence interval (CI) of 0.74-0.88) on a held-out test set, while CAD software alone achieves an AUC of 0.69 (CI 0.60-0.78). We also identify that invasive breast cancers have a unique compositional signature characterized by reduced lipid content and increased water and protein content when compared to surrounding tissues. Conclusion: Clinically, 3CB may potentially provide increased accuracy in predicting malignancy and a feasible avenue to explore compositional breast imaging biomarkers.