PROJECT SUMMARY/ABSTRACT This grant application proposes to use the unique stationary Multi-X-ray-source Array (MXA) technology developed and applied to digital breast tomosynthesis (DBT) under our current R01 to: 1) significantly improve DBT image quality by extending the MXA technology to produce a clinically practical two-dimensional (2D) MXA and 2) demonstrate a capable and fully characterized 2D MXA DBT system to use for clinical trials under a follow-on R01 Academic–Industrial Partnership program. By the time the first film-based commercial tomosynthesis systems were developed in the 1970s, it was realized that 2D motion of the X-ray source significantly improved image quality relative to 1D motion due to better blurring of the shadows of structures both above and below the plane of interest. All existing commercial DBT systems use 1D motion because 2D mechanical motion is complicated and expensive and would significantly increase scan times which are already too long at 4 to 25 s with the 1D motion-based systems. Compare this to mammography, where it is preferred to keep scan times under 2 s to minimize patient-motion artifacts. Extending MXA technology to make 2D breast tomosynthesis practical – by meeting scan time constraints – will provide superior performance compared with all commercial breast tomosynthesis systems on the market today, while at the same time decreasing system size and cost. The net result would be a significant increase in the capability of DBT systems and a broadening of their availability to bring better care to more people sooner. The Specific Aims of this application are: Aim 1. Use modeling and experiments to design the 2D MXA-DBT prototype system Aim 2. Build 2D MXA DBT prototype system Aim 3. Evaluate performance of 2D MXA DBT prototype system