Abstracts

Rationale: In vivo (11.1 Tesla) and excised (17.6 Tesla) MR relaxation times (T1 and T2) and diffusion tensor imaging were employed to determine the structural changes within the hippocampus and parahippocampus prior to onset of spontaneous seizures, during the ‘latent’ period of epileptogenesis in a rat model of mesial temporal lobe epilepsy.Methods: A pair of 50µ gold plated tungsten wires was stereotactically implanted in the right ventral hippocampus of 50 day old Sprague Dawley rats. Rats (n=7) were electrically stimulated to induce status epilepticus (SE). One other rat served as implanted control and two as naïve controls. Their behavior was continuously video monitored starting within three weeks post-SE. Longitudinal in vivo MRI scans were obtained pre electrode implantation, post electrode implantation, and at 3, 5, 7, 10, 20, 40 and 60 days post-SE. Following in vivo imaging, intact excised brains were imaged. Diffusion weighted images (DWI’s) were acquired with a spin echo sequence using 6 low b-value and 21 high b-value gradient directions for in vivo and, 6 low b-value and 46 high b-value directions for excised. The DWI’s were fit to a rank-2 apparent diffusion tensor model at each voxel. To quantify relaxation, coronal T1 and T2-weighted images were measured consecutively with the following parameters: TR, 4000, 2000, 1000, 500, 250 ms and TE, 15 ms for T1 measurements; TR, 2,000 ms and TE, 15, 30, 45, 60, 75 ms for T2 measurements.Results: Five rats developed spontaneous seizures at 19.8 ± 6.5 days post-SE. Quantitative average diffusivity (AD), fractional anisotropy (FA), T1 and T2 data from ROIs’ in each rat were analyzed. By comparison of pre-implant data, variability for all rats was found to be low for AD but high for FA measurements. Control rats did not show a significant change in their AD and FA values over time. Increased AD in stimulated rats was observed bilaterally in vivo, in the entorhinal and piriform cortices, amygdala and the lateral aspects of the hippocampus (Fig. 1) as early as 3 days post-SE and persisted through the 60 days. Lower FA was also observed in the fimbria (Fig. 1) in excised imaging. Significantly increased T1 and T2 values were observed in the amygdala and piriform cortex, more intense on the contralateral side to stimulation between 3 and 20 days post-SE (Fig. 2). In addition, excised imaging showed significantly decreased T2 in the hippocampus and the dorsal thalamic nuclei bilaterally. Histological analysis of these rats revealed mossy fiber sprouting in the dentate gyri, as well as demyelination and astroglial cell proliferation in the hippocampus, and neurodegeneration in the amygdala and piriform cortices on the side contralateral to stimulation.Conclusions: MR changes were visible bilaterally before the onset of spontaneous seizures more in the parahippocampus regions then the hippocampus. Increase in T2 and AD values suggests vasogenic edema and demyelination in the affected regions which correlates with histological findings. Supported by: NIH grants, R01 EB004752 and R01 NS42075, Wilder ERC, UF Alumni Foundation