Influence of the normalization template on the outcome of statistical parametric mapping of PET scans

Spatial normalization is an essential preprocessing step in statistical parametric mapping (SPM)-based analysis of PET scans. The standard template provided with the SPM99 software package was originally constructed using (15)O-H(2)O PET scans and is commonly applied regardless of the tracer actually used in the scans being analyzed. This work studies the effect of using three different normalization templates in the outcome of the statistical analysis of PET scans: (1) the standard SPM99 PET template; (2) an (18)F-FDG PET template, constructed by averaging PET scans previously normalized to the standard template; and (3) an MRI-aided (18)F-FDG PET template, constructed by averaging PET scans normalized according to the deformation parameters obtained from MRI scans. A strictly anatomical MRI normalization of each PET was used as a reference, under the rationale that a normalization based only upon MRI should provide higher spatial accuracy. The potential bias involved in the normalization process was estimated in a clinical SPM study comparing schizophrenic patients with control subjects. For each between-group comparison, three SPM maps were obtained, one for each template. To evaluate the influence of the template, these SPM maps were compared to the reference SPM map achieved using the anatomical normalization. SPMs obtained by MRI-aided normalization showed the highest spatial specificity, and also higher sensitivity when compared to the standard normalization using the SPM99 (15)O-H(2)O template. These results show that the use of the standard template under inappropriate conditions (different tracer or mental state) may lead to inconsistent interpretations of the statistical analysis.