Medical imaging systems like full field digital mammography (FFDM) and digital breast tomosynthesis (DBT) commonly use amorphous selenium (a-Se) based passive pixel sensor (PPS) direct conversion x-ray detectors. On one hand, direct conversion detectors inherently offer better resolution characteristics in terms of a higher modulation transfer function (MTF), in comparison to the indirect CsI:Tl PPS x-ray imager. On the other hand, especially at lower doses, this superior performance of the direct imager is seldom retained in its detective quantum efficiency (DQE) curves.It is well known that a-Se PPS x-ray imagers suffer from high additive electronic noise originating from the from the amorphous silicon (a-Si) thin film transistor (TFT) array that is being used in the current back-plane technology. This degrades the noise power spectrum (NPS) and subsequently the overall DQE. To address this deficiency, we propose to replace the PPS back-plane by active pixel sensor (APS) back-plane technology, which has the potential to reduce the back-plane electronic noise by amplifying the input signal, especially at low doses. The proposed APS is based on amorphous In–Ga–Zn–O (a-IGZO) TFT technology, which can offer high mobility (5–20 cm2 V−1 s−1), low leakage current (<10−13 A) and low flicker noise (Hooge’s parameter αH ~ 1.5 10−3), leading to better imager noise performance.To test our hypothesis, we used linear cascaded systems analysis to model the imaging performance (MTF, NPS and DQE) of the PPS and APS a-Se direct imagers. This model was first validated using experimentally measured data obtained for a 85 µm pixel pitch a-Se/a-Si TFT PPS imager. Using this model, we analyzed the noise performance of the direct a-Se and indirect CsI:Tl x-ray a-IGZO APS imagers at different dose and electronic noise levels. Obtained results clearly showed that lowering back-plane electronic noise can significantly improve the performance of the a-Se/a-IGZO TFT APS imager. Our simulated results showed that a higher DQE at lower radiation doses (maximum DQE of 0.6 can be achieved at an exposure level of 1 µGy) can be achieved with the a-Se detector, thereby making this combination a promising candidate for low dose applications like DBT.