We describe a multi-layer ("sandwich") configuration detector consisting of two x-ray imaging flat-panel detectors for single-shot (single-kV) dual-energy imaging. An intermediate copper filter is used to increase spectral separation between the two detectors to improve contrast at the expense of image noise. Monte Carlo and cascaded-systems analyses of the signal and noise performance are described that quantify performance characteristics. Image quality of dual-energy images obtained from a prototype sandwich-detector system is evaluated using a figure of merit (FOM), defined as the squared contrast-to-noise ratio normalized by x-ray exposure for a mouse phantom for preclinical imaging. Demonstration dual-energy bone and soft-tissues images of a postmortem mouse are obtained using the prototype system. While the FOM with the single-shot detector is lower than that achieved using a conventional dual-shot (dual-kV) method, the single-shot approach may be preferable when imaging speed or insensitivity to motion artifacts is a primary concern. (C) 2014 Elsevier B.V. All rights reserved.