Abstract: Methods and systems for facilitating combined co-registration and image pixel calibration of multimodal data are provided. According to one embodiment, a first set of digital image data is received that includes pixel data associated with a portion of a patient's anatomy and a fiducial system. A second set of digital image data is received that includes pixel data associated with the portion of the patient's anatomy and the fiducial system. One or both of the sets of digital image data are adjusted, calibrated, modified or verified based on known characteristics of the fiducial system. A composite model of the portion of the patient's anatomy is generated by co-registering the two sets of digital image data based on the pixel data associated with the fiducial system.