Breast cancer is a major health concern in the United States. Mammography is the gold standard for screening breast cancer and screen-film technology is still widely used in the screening for breast cancer. However, screen-film systems have limited dynamic range and contrasts compared to digital systems, and do not offer integrated image processing capabilities. Recently, digital mammography has seen an upsurge in clinical adoption but current digital mammography systems are limited in terms of their spatial resolution. Therefore, high-resolution digital mammography systems with superior signal-to-noise ratio and contrast characteristics need to be explored. A monolithic, single module high-resolution (39 um) digital x-ray platform (Fairchild Imaging Inc., Milpitas, CA) was developed and characterized for digital mammography. The architecture was extended to a large area (16 x 24-cm) multi-module solid-state imager with variable resolution (39 and 78-um). In addition, a four module (16 x 16-cm) imaging architecture with 78-um pixel was explored for high-resolution contrast enhanced digital mammography for the detection of malignancy-associated angiogenesis. Simulations based on the cascaded linear systems framework were performed in order to characterize the physical properties of the imaging platforms such as the modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE). Experimental measurements of imager performance was also conducted and compared to model predicted results. Further, perceptual analysis of the prototype imaging platform for digital mammography was performed. Various imaging platforms were successfully developed and investigated to identify essential parameters for high-resolution digital x-ray breast imaging. The single module prototype exhibited physical characteristics that are favorable for digital mammography. Good agreement between model and experimental results were observed demonstrating the utility of such models for further system improvement. The large area 16 x 24-cm prototype demonstrated superior contrast-detail characteristics compared to a clinical FFDM system (100 um pixel) at both 39 and 78-um pixel sizes. Both experimental and theoretical results pointed towards the feasibility of contrast enhanced mammography at mean x-ray glandular dose levels substantially lower than mammography under the conditions investigated. Qualitative analysis of contrast enhanced digital mammography indicated favorable image quality.