Comparison of Statistical Parametric Mapping and SPECT Difference Imaging in Patients with Temporal Lobe Epilepsy *David J. Chang, ²I. George Zubal, ‡Chris Gottschalk, ‡Alejandro Necochea, ²Rik Stokking, ²Colin Studholme, ²Maria Corsi, ²Jessica Slawski, ‡Susan S. Spencer, and *‡Hal Blumenfeld *Section of Neurobiology, Departments of ²Diagnostic Imaging and ‡Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A. Summary: Purpose: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conven- tional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictal– interictal difference imaging in clinical epilepsy has been vali- dated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epilepto- genic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study. Methods: Twelve patients with pairs of periictal and interic- tal SPECT scans were analyzed in this comparison study be- tween SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hip- pocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in con- trast to our control group. Results: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with re- gions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the correspond- ing epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods. Conclusions: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal–interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy. Key Words: Epi- lepsy—Periictal SPECT—CBF difference imaging—Statistical parametric mapping (SPM). Single-photon emission computed tomography (SPECT) provides important clinical information mea- suring regional cerebral blood flow changes in the evalu- ation of epileptic seizure foci. In general, SPECT has demonstrated hyperperfusion in the epileptogenic region periictally and hypoperfusion interictally. Zubal et al. (1) demonstrated improved localization using SPECT differ- ence imaging, whereby interictal images are subtracted on a voxel-by-voxel basis following co-registration and normalization with ictal images. However, the limitation of this approach as with most others remains its degree of interobserver variability (1–3). Other methods of SPECT interpretation have increased diagnostic yield. Calcula- tion of asymmetry indices between regions of interest (ROIs) and reference regions (semiquantitative analysis) has been performed by some investigators (4–6). Statistical parametric mapping (SPM) is an increas- ingly established form of neuroimaging analysis to lo- calize statistically significant changes in spatially normalized images on a voxel-by-voxel basis (7,8). Working within a standardized stereotactic space, SPM removes the subjectivity inherent in quantitation based on visual analysis. SPM has been applied to temporal lobe epilepsy including in the evaluation of SPECT (9). The purpose of this study was to determine the value of SPM in the analysis of ictal–interictal differences among a surgically defined group of temporal lobe epilepsy pa- tients from our database in comparison with a technique our group established of SPECT ictal–interictal differ- ence imaging. Revision accepted November 28, 2001. Address correspondence and reprint requests to Dr. H. Blumenfeld at Department of Neurology, Yale University School of Medicine, New Haven, CT 06501, U.S.A. E-mail: hal.blumenfeld@yale.edu Epilepsia, 43(1):68–74, 2002 Blackwell Publishing © International League Against Epilepsy 68