Abstracts

Rationale: Metabotropic glutamate receptor type 5 (mGluR5) modulates neuronal excitability and synaptic plasticity in the healthy brain. Pathological studies of surgical specimens from patients with epilepsy suggest that mGluR5 is upregulated in focal cortical dysplasias (FCD). However, resected foci provide only a limited glimpse of molecular and structural abnormalities within the epileptic brain, limited by the scope of the surgical resection. It is now possible to access in vivo whole brain mGluR5 availability with positron emission tomography (PET) using the radioligand [11C] ABP688, which binds specifically to the transmembrane allosteric site of mGluR5. This is a first study to evaluate [11C] ABP688 binding potentials (BP) in patients with FCD. Methods: Five patients with radiologically confirmed FCD and epilepsy (4 female, mean age ± SD of 41 ± 9 years), and 14 healthy controls (6 female, mean age ± SD of 46 ± 19 years) were included in the study. [11C]ABP688 PET scans consisted of a 1hour dynamic acquisition following [11C]ABP688 injection, in the HR+ ECAT PET scanner. Images were reconstructed using filter-back projection. PET volumes were coregistered to each subjects's T1-weighted 3T MRI and resampled to standard space. [11C]ABP688-BP maps were generated using a simplified reference tissue method with the cerebellum as a reference region. A voxel-wise whole brain z-test of [11C]ABP688-BP was performed between each FCD patient and the control group. Multiple comparison correction was conducted separately for the lobe ipsilateral to the lesion and for the remaining cortex using a cluster-based random field theory method. Each cluster had a minimum voxel threshold of p<0.001. Results: Gender and age were not significantly associated with [11C]ABP688-BP. Visual inspection of [11C]ABP688-BP maps suggested reduced binding within the FCD topography. Therefore, for quantitative analysis, we manually segmented the grey matter of the dysplastic lesion, the grey matter of the lobe ipsilateral to the FCD, and the remaining cortex. Voxel-wise analysis confirmed a greater percentage of negative z-scores within the area of FCD and within the lobe ipsilateral to the FCD relative to the rest of the cortex. Positive z-scores were not found within the FCDs but were observed in a scattered pattern, unspecific to the FCD location. Conclusions: Our findings in this small group of patients confirm abnormal mGluR5 availability in patients with FCD, as previously suggested by pathological studies. The results show additional areas of reduced binding, anatomically adjacent to the FCD lesion. Increased binding seemed less structurally specific and less related to the FCD. In vivo mGluR5 availability may aid radiological diagnosis/confirmation in patients with suspected MCDs. Supported by the Savoy Foundation