Crystalline silicon (c-Si) technology is attractive for advanced large area imaging applications because of higher transistor mobility, smaller feature sizes and higher density of integration. In particular, for advanced mammography modalities such as tomosynthesis, c-Si is ideally suited to develop the high performance circuitry required for higher contrast, lower noise, and lower X-ray dose, while providing high resolution pixels. We present a voltage-mediated active pixel sensor (APS) with a focus on large area, diagnostic medical X-ray tomographic mammography. System level noise calculations indicate that CMOS technology can meet the stringent noise and area requirements required for tomographic mammography.