Abstracts

Rationale: Epileptogenesis is associated with dynamic changes in brain structure, function and metabolism. Better understanding of the evolution of these changes after the initiating brain insult and correlation with electrophysiological and histopathological characteristics may yield insights into the mechanisms underlying the development of epilepsy and better predictors of outcome. We studied the evolution of changes in brain structure following status epilepticus in a mouse model of temporal lobe epilepsy (TLE) using ultra high-field MRI and voxel-based analyses of multi-echo T2 and diffusion weighted imaging (DWI).Methods: We studied 3 groups of Swiss CD-1 mice comprising controls (CN, n=6), those with status epilepticus (SE, n=8) following injection of pilocarpine, and those that did not develop status epilepticus following injection (NS, n=7). MR images were acquired at 1 (D1), 2 (D2), 14 (D14) and 35 (D35) days after the injection. The T2 time and apparent diffusion coefficient (ADC) were calculated. Skull stripping for these images was performed using a knowledge-guided active contour method. T1 images were then registered to an averaged mouse brain template using normalized mutual information and nonlinear B-spline registrations. The resultant transformation matrices were used to normalize the T2 and ADC. Registered images were smoothed with a 1mm FWHM Gaussian kernel. Statistical parametric mapping with SPM8 was used to compare ADC and T2 maps between the three groups. Regions of interest were also defined using the Brookhaven mouse atlas registered to each mouse brain. Group comparisons of average ADC and T2 values in each structure were performed. For each image type, the fractal dimension (FD) of each structure was calculated according to the fractal Brownian model.Results: SPM: The threshold for statistical significance was set at a family-wise error < 0.05. In the SE group, ADC was reduced in the hippocampus (HC) and thalamus at D1 and subsequently recovered. In the NS group, ADC and T2 values were elevated in HC and amygdala (AMG) on D2 and returned to normal by D14. In the SE group both ADC (Fig.1) and T2 (Fig.2) were elevated in the parahippocampal cortex at later time points and in the HC and AMG at both early and late time points. Regions of interest: ADC values were elevated in thalamus consistent with the SPM findings (p < 0.04) (SE and NS vs. CN) but there were no significant group differences in T2. In the SE group, the FD of ADC maps was significantly elevated in the HC at D1 and D2 (p< 0.04) and the FD of T2 in the neocortex and AMG was significantly decreased at D1 (p< 0.03). Conclusions: Reversible changes were observed in HC and AMG in the NS group with recovery after 14 days. Persistent changes were observed in HC, AMG, and parahipocampal cortex following SE at different latencies. This temporal pattern most likely reflects the evolution of pathological changes underlying the development of TLE from neuronal swelling and cytotoxic edema to gliosis.