Abstracts

Rationale: The intrahippocampal kainic acid (IHKA) rat model is a model for Mesial Temporal Lobe Epilepsy with hippocampal sclerosis, the most frequent form of human symptomatic epilepsy. Although the histopathological changes in the hippocampus in response to KA injection are well characterized, changes in other brain regions are less known. We have investigated the metabolic and structural changes in the complete brain in the IHKA model using dynamic FDG-PET and T2-weighted (T2w) MRI at 7T.Methods: A cannula was stereotactically placed in the right intermediate hippocampus (AP=-5.6 mm, ML=+4.5 mm, DV=-5.5 mm relative to bregma) of 13 Sprague Dawley rats (male, 300g). One week later, imaging was performed on three consecutive days. On day 1 a baseline T2w MRI was acquired. Then a dynamic PET acquisition with continuous infusion of 18F-FDG was performed. First a 300 uCi bolus was administered followed by continuous adjustment of the infusion rate, which allows to visualize changes in cerebral glucose metabolism during 180 minutes. This is not possible with standard single-bolus FDG-PET. 90 min after the start of the PET scan KA (0.4 g/0.1 l; 0.1 l/min, n=9) or saline (0.1 l/min, n=4) was injected. T2w MRI scans were acquired at 2h, 24h and 48h after injection. The average normalized MR intensity was calculated for each rat in 9 brain structures bilaterally. PET images were reconstructed in 10 min frames. The right-to-left FDG uptake ratio (UR) was calculated in each frame in the same 9 structures. For each structure, a linear mixed model was fit to the PET and MR data separately, using group and time as fixed effects.Results: After KA injection a a significant increase (p < 0.05) in FDG UR was seen in the ipsilateral hippocampus, entorhinal cortex, amygdala, thalamus, neocortex and striatum (fig. 1). 2h after KA injection, all animals showed an increase in T2w signal in the right hippocampus only. At 24h and 48h after KA injection, average T2w MR intensity was significantly different from baseline in ipsilateral hippocampus, entorhinal cortex, amygdala and septum (fig. 2). A subset of the animals also showed increased T2w MR signal in ipsi- and/or contralateral thalamic nuclei and piriform cortex and in contralateral hippocampus and amygdala. No significant changes were seen in the saline group except an increased FDG UR in the neocortex, probably due to inflamation at the injection site.Conclusions: Intrahippocampal injection of KA induces an immediate strong increase in glucose uptake in the ipsilateral hippocampus but also in the ipsilateral entorhinal cortex. At 24h and 48h post-injection, the pattern of changes in T2w MR images showed a high interindividual variability. This may be related to the variability in seizure frequency and generalization that has been observed in this model.