A method to register a subject space defined by a subject having an attached imageable fiducial assembly to an image space, comprising: acquiring (i) a plurality of two-dimensional x-ray projection image data of the subject with an imaging device of an imaging system , and (ii) selected parameters of the imaging system for each of the plurality of two-dimensional x-ray projection image data; generating a three-dimensional reconstruction of at least a portion of the subject based on at least a portion of the acquired plurality of two-dimensional x-ray projection image data; determining a number of identifiable portions of the imageable fiducial assembly in the three-dimensional reconstruction; and in response to the number of identifiable portions of the imageable fiducial assembly being less than a predetermined number, selecting at least one of the plurality of acquired two-dimensional x-ray projection image data that includes a selected portion of the imageable fiducial assembly, recalling from a storage device the selected parameters of the imaging system relating to the selected at least one of the plurality of acquired two-dimensional x-ray projection image data, determining a position of a fiducial feature of the imageable fiducial assembly based on the recalled selected parameters of the imaging system, and registering the subject space to the image space based on the selected at least one of the plurality of acquired two-dimensional x-ray projection image data and the determined position of the fiducial feature, wherein determining the position of the fiducial feature of the imageable fiducial assembly includes generating a synthetic digital radiograph reconstruction of the imageable fiducial assembly for parameters similar to the recalled selected parameters of the imaging system. acquiring (i) a plurality of two-dimensional x-ray projection image data of the subject with an imaging device of an imaging system , and (ii) selected parameters of the imaging system for each of the plurality of two-dimensional x-ray projection image data; generating a three-dimensional reconstruction of at least a portion of the subject based on at least a portion of the acquired plurality of two-dimensional x-ray projection image data; determining a number of identifiable portions of the imageable fiducial assembly in the three-dimensional reconstruction; and in response to the number of identifiable portions of the imageable fiducial assembly being less than a predetermined number, selecting at least one of the plurality of acquired two-dimensional x-ray projection image data that includes a selected portion of the imageable fiducial assembly, recalling from a storage device the selected parameters of the imaging system relating to the selected at least one of the plurality of acquired two-dimensional x-ray projection image data, determining a position of a fiducial feature of the imageable fiducial assembly based on the recalled selected parameters of the imaging system, and registering the subject space to the image space based on the selected at least one of the plurality of acquired two-dimensional x-ray projection image data and the determined position of the fiducial feature, <EOS>