A system provides a multi-axis translation and orientation capability for optical imaging. The system includes an optical imaging apparatus providing a signal representing a digitized image, and a mechanical frame. The frame includes a first set of articulations capable of independently translating the optical imaging apparatus in multiple linear directions. The system also includes a second set of articulations formed as joints providing at least three independent degrees of rotation of the optical imaging apparatus. The system also provides an opening configured to permit the frame to be postured about a patient such that an isocenter corresponds to a region of interest of the patient, and includes an illumination source attached to the frame and configured to direct illumination towards the isocenter. The system also comprises a camera system co-located with the illumination source and having a focal plane at the isocenter.