Systems and methods for x-ray tomosynthesis image reconstruction

Imaging systems comprising x-ray image reconstruction systems combined with optical imaging and/or tracking systems. In some embodiments, the imaging system may comprise an x-ray image reconstruction system configured to generate three-dimensional image data of at least an internal portion of a target object under a surface of the target object and a three-dimensional optical imaging system configured to reconstruct an image of at least a portion of the surface of the target object by generating surface three-dimensional image data. The three-dimensional optical imaging system may be registered to the x-ray tomosynthesis image reconstruction system such that three-dimensional image data from the x-ray tomosynthesis image reconstruction system and three-dimensional image data from the three-dimensional optical imaging system may be used as a constraint to improve image quality of an image of the target object.