The present invention involves relating in real time the three-dimensional location and orientation of a surgical site (600, 720) to the location and orientation of the surgical site in a scan of the surgical site. By taking a scan of the surgical site to obtain scan data (820), the three-dimensional location and orientation of a natural fiducial reference (780) may be determined from the scan data (840). Real time image information of the surgical site (850) may then be obtained to determine in real time the three-dimensional location and orientation of the natural fiducial reference from the image information (860). This allows for deriving a spatial transformation matrix for expressing in real time the three-dimensional location and orientation of the natural fiducial reference as determined from the image information in terms of the three-dimensional location and orientation of the natural fiducial reference as determined from the scan data (870).
