Abstracts

Rationale: In acquired epileptogenesis, the initial brain damaging insult results in several neurobiological alterations that eventually lead to the occurrence of spontaneous seizures, including axonal sprouting. Previous studies suggest that in some models these alterations can occur even before the occurrence of spontaneous seizures (Nissinen J. et al, Hippocampus, 2003; Kharatishvili et al., 2006). Axonal sprouting can be detected using manganese-enhanced MRI (Nairismägi J et al, Neuroimage 2006). However, the use of manganese as a contrast agent is not clinically feasible because of its toxicity, and therefore, there is a need for non-invasive methods for detecting early markers of epileptogenesis. This study demonstrates the capability of diffusion tensor imaging (DTI) to detect changes in the dentate gyrus (DG) of the rat hippocampus after kainic acid (KA) -induced status epilepticus.Methods: Status epilepticus was induced in male Wistar rats (n=6) with kainic acid (10 mg/kg, i.p.). Controls received saline (n=5). Four months after status epilepticus, animals were perfused intracardially using Timm fixation for histological detection of mossy fiber sprouting in the DG. Prior to DTI, brains were immersed into perfluoro polyether to prevent signal from the solution. DTI experiments were carried out in a 9.4 T magnet interfaced with a Varian console using a quadrature volume RF-coil for transmitter and receiver. Data were acquired using a 3D spin echo sequence (TR=1 s, TE=60 ms, data matrix 192×64×64 zero padded to 192×128×128, FOV 23×15×15 mm3). Six 3D data sets with diffusion weighting (diffusion time 17 ms, b-value 1000 s/mm2) in six orthogonal directions and one data set without diffusion weighting were obtained. From the measured 3D data sets a diffusion tensor, a matrix describing the orientation dependence in each voxel was determined. Maps of fractional anisotropy (FA), describing the isotropy of diffusion, and color-coded FA maps showing the directionality of diffusion were created. Results: Analysis of 6 FA maps indicated an increased volume of the septal DG in rats with status epilepticus (0.44 mm±0.04 mm3, mean + SD) as compared to controls (0.70±0.12 mm3, p<0.01, Fig 1). FA volumes correlated with the score indicating the density of mossy fiber sprouting in sections corresponding to the slices used for FA analysis (r=0.86, p<0.01).Conclusions: The increase in the volume of the DG as determined from FA maps suggests that mossy fiber sprouting influences water anisotropy and thus becomes detectable by DTI. As DTI is a completely non-invasive technique and commonly used in clinical settings, our observations can have implications for detection of the mossy fiber sprouting in patients at risk of epileptogenesis after brain trauma.