Image subtraction is widely used in angiography as a means of highlighting differences induced by contrast agents. New knowledge of previously unsuspected causes of disease, in particular, secondhand smoke exposure, spurs interest in pushing the limits of early accurate diagnosis. Simple image subtraction induces artifacts causing problems for ensuing measurements and 3D reconstruction. Image registration techniques have been used to partially solve this problem. However, a complete registration is slow, and misregistration often occurs in images where bones are surrounded by vessels with similar image characteristics. We propose an approach based on the idea of global match followed by local refinements. In the global match, an image pair is aligned using a similarity measure so as to reduce overall difference. In the local refinements, localized displacements and deformations of tissue are handled by a combination of techniques: image registration, region growing, erosion, and dilation. This approach is fast compared to registration based image subtraction and it can find vessels abutting a bone. It is designed to be especially suitable for large cross-section image stacks. With additional vessel connectivity analysis between adjacent slices, the algorithm provides a good foundation for 3D vessel reconstruction.