A system for selectively disabling a surgical instrument operating in a surgical site of a region of interest of a living subject. In one embodiment, the system includes means for noninvasively placing a number of fiducial markers in an anatomic space of the region of interest of the living subject, means for pre-operatively measuring a location of each fiducial marker in the anatomic space, an imaging acquisition device for pre-operatively acquiring an image volume from the region of interest of the living subject, a probe for intra-operatively monitoring a location of the surgical instrument in the anatomic space, and a controller configured to perform the steps of identifying a centroid of each fiducial marker in the image volume, registering the identified centroid of each fiducial marker in the image volume to the measured location of the corresponding fiducial marker in the anatomic space to determine a registration transformation, mapping the monitored location of the surgical instrument in the anatomic space onto a corresponding location in the image volume by an inverse of the registration transformation, and generating a signal to disable the surgical instrument when the mapped location of the surgical instrument is substantially close to a boundary of the surgical site of the region of interest in the image volume.