X-ray mammography is a crucial screening tool for early identification of breast cancer. However, the overlap of anatomical features present in projection images often complicates the task of correctly identifying suspicious masses. As a result, there has been increasing interest in acquisition of volumetric information through digital breast tomosynthesis (DBT) which, compared to mammography, offers the advantage of depth information. Since DBT requires acquisition of many projection images, it is desirable that the noise in each projection image be dominated by the statistical noise of the incident x-ray quanta and not by the additive noise of the imaging system (referred to as quantum-limited imaging) and that the cumulative dose be as low as possible (e.g., no more than for a mammogram). Unfortunately, the electronic noise (~2000 electrons) present in current DBT systems based on active matrix, flat-panel imagers (AMFPIs) is still relatively high compared with modest x-ray gain of the a-Se and CsI:Tl x-ray converters often used. To overcome the modest signal-to-noise ratio (SNR) limitations of current DBT systems, we have developed a large-area x-ray imaging detector with the combination of an extremely low noise (~20 electrons) active-pixel CMOS and a specially designed high resolution scintillator. The high sensitivity and low noise of such system provides better SNR by at least an order of magnitude than current state-of-art AMFPI systems and enables x-ray indirect-detection single photon counting (SPC) at mammographic energies with the potential of dose reduction.