Large area digital imaging made possible by amorphous silicon thin-film transistor (a-Si TFT) technology, coupled with a-Si photo-sensors, provides an excellent readout platform to form an integrated medical image capture system. Major development challenges evolve around optimization of pixel architecture for detector fill factor, and manufacturability, while suppressing noise stemming from pixel array and external electronics. This work discusses the behavior and modeling of system noise that arises from imaging array operations. An active pixel sensor (APS) design with on-pixel amplification is studied. Our evaluation demonstrates that a 17 inch by 17 inch array can achieve system noise as low as 1000 electrons through proper design and optimization.