A method for performing 2D/3D registration includes acquiring a 3D image. A pre-contrast 2D image is acquired. A sequence of post-contrast 2D images is acquired. A 2D image is acquired from a second view. The first view pre-contrast 2D image is subtracted from each of the first view post-contrast 2D images to produce a set of subtraction images. An MO image is generated from the subtraction images. A 2D/3D registration result is generated by optimizing a measure of similarity between a first synthetic 2D image and the MO image and a measure of similarity between a second synthetic image and the intra-operative 2D image from the second view by iteratively adjusting an approximation of the pose of the patient in the synthetic images and iterating the synthetic images using the adjusted approximation of the pose.
