Peri-ictal SPECT is a potentially powerful tool to study changes in regional cerebral blood flow during a partial seizure and to localize the seizure focus for pre-surgical evaluation. Recently we have developed and validated a method for co-registering and normalizing 3D interictal SPECT images to 3D ictal SPECT images and deriving a difference image co-registered to the patient's 3D MRI. This method has been shown to significantly improve clinical outcomes in surgery patients. In order to improve the method's sensitivity and specificity a number of enhancements have been added to the basic technique, including using voxel-based registration to better alignictal and interictal images, dual isotope (Tc-99m and 1-123) SPECT for effective tissue discrimination, and a custom software interface written to facilitate the entire process. We report results that show significant improvement over the original method, and we discuss future work which should continue to improve the method as a clinical tool.