1. A method of 3D-2D registration for medical imaging, the method which comprises: a) providing a first input interface for acquiring a three-dimensional image; b) providing a second input interface for acquiring a fixed two-dimensional image using an imaging system comprising a source and a detector and having an unknown source-detector geometry; c) initializing image transformation parameters and source-detector geometry parameters; d) generating a reconstructed two-dimensional image from the three-dimensional image using the image transformation parameters and the source-detector geometry parameters; e) determining an image similarity metric between the fixed two-dimensional image and the reconstructed two-dimensional image; and f) updating the image transformation parameters and the source-detector geometry parameters using the image similarity metric.