The availability of genetically altered mouse models of human disease and the increasing use of small animals in basic research have spurred extraordinary interest in new imaging methodologies - particularly magnetic resonance microscopy, microCT, and microPET. To date, very little attention has been given to planar radiographic imaging. Yet there exists enormous potential for this modality given the ease of use and its potential speed. Functional imaging in mouse models can be addressed particularly well through the use of digital subtraction angiography. We describe here a system designed explicitly for digital subtraction angiography in the mouse and the optimization of acquisition parameters required to perform the highest quality functional subtraction angiograms. We focus on optimization of contrast using selective K-edge filters and the optimization of contrast agent though a carefully controlled biological pulse sequence.