CORTICAL GREY-MATTER AND BENZODIAZEPINE RECEPTORS IN MALFORMATIONS OFCORTICAL DEVELOPMENT - A VOXEL-BASED COMPARISON OF STRUCTURAL AND FUNCTIONAL IMAGING DATA

Using [C-11]flumazenil-PET and statistical parametric mapping (SPM), w e have shown recently that regions of increased and decreased benzodia zepine receptor density may be seen in patients with localization-rela ted epilepsy due to malformations of cortical development. These abnor malities were seen both within and beyond lesions visually apparent on high-resolution MRI. We have also shown, using an interactive anatomi cal segmentation technique and volume-of-interest measurements, that s ubtle and unsuspected abnormalities of cortical grey matter volume wer e found in the same group of patients on high-resolution MRI, beyond t he lesions visually apparent. In 10 patients with localization-related epilepsy and malformations of cortical development, we have now appli ed the automated and objective technique of SPM to the analysis of hig h resolution structural MRI. Each individual patient was compared with 16 normal control subjects. We have then simultaneously compared the structural and functional data obtained for each individual patient wi th normal control high-resolution MRI and [C-11]flumazenil-PET images using a novel technique. This comparison allowed the detection of func tional abnormalities that were not accounted for by either visible or unsuspected structural abnormalities, in an automated and statisticall y rigorous manner Five patients had abnormalities of cortical grey mat ter volume detected using SPM; only these five patients had been found abnormal using the previous volume-of-interest technique. Six of the 10 patients showed regions of cerebral cortex with disproportionate fl umazenil binding compared with local grey matter volume. This included regions not found to have abnormal flumazenil binding on analysis of the PET data alone. Furthermore, regions found to have abnormal bindin g on examination of the PET data alone were, in some instances, shown to be accounted for by abnormalities of cortical grey matter volume. W e conclude that the analysis of ligand PET data should always include a comparison with structural MRI; such comparisons are greatly facilit ated by the novel approach described.