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One major deficiency of standard mammography is the camouflaging effect of overlapping structures in the projection images that limits the rendering of breast cancer. To minimize this effect, we proposed Multi-plane Correlation Imaging (MCI) technique. In this technique, multiple radiographic images of the breast are obtained from different angles. Angular information is used to identify and positively reinforce the lesion signals between different projections. In this phase of the study, we conducted a feasibility study of MCI using a mathematical model-based framework. Clinical utility of MCI was tested using a task that modeled clinical practice on clinically-realistic backgrounds of mastectomy specimens. The technique was then optimized to obtain maximum diagnostic information. Furthermore, a CADe based operator that takes advantage of the MCI configuration was developed. Results revealed that the peak performance for MCI at dose levels of one- and two-view mammography was achieved at 15 ? 17 projections spanning an angular arc of ~45o, the widest angle tested in this study. Performance of optimized MCI exceeded that of standard mammography by 18%. Overall, MCI may prove to be potentially more accurate, and cost-and dose-effective., The original document contains color images.