Abstracts

RATIONALE: Fundamental to the study of epilepsy are questions about the anatomic location of seizure origination and pathways of seizure propagation through the brain. Classically, electrophysiologic measures have been used to study seizure origination and propagation. There are now magnetic resonance (MR) imaging correlates of neuronal activity that may be used to observe (indirectly) activation of anatomically distinct areas of the brain. By taking advantage of blood oxygen level dependent (BOLD) contrast imaging techniques, we sought to determine if the onset and propagation of seizures can be observed in a small animal (rat) model of epilepsy.
Objective: The participant should appreciate the potential for application of fMRI to small animal models of epilepsy.
METHODS: We have obtained BOLD fMRI data following the systemic administration of a convulsant, either pentylenetetrazol (PTZ, 50 mg/kg, n = 5) or kainic acid (KA, 15mg/kg, n= 5) at a dose that induces generalized seizures in rats. Animals were anesthetized preceding placement of intra-arterial, venous and peritoneal catheters. Artificial ventilation was used throughout the experiment and arterial blood gases were monitored. Using a single shot gradient echo planar imaging (EPI) technique, 5 slices were acquired every 2 seconds over the time course of the study. We defined the initiation of seizure activity as the occurrence of a statistically significant (p[lt]0.0001, unpaired t-test) increase in baseline pixel intensity, using a simple step function and two10 acquisition windows. Propagation of seizure activity was measured by comparison with pre-seizure baseline using the same statistical parameters.
RESULTS: In comparing the two convulsants, we observed activation of anatomic areas that agreed with expectations based upon known receptor distribution and information from other modalities (i.e. PET). After PTZ treatment, activation was found primarily in periventricular thalamus and diffusely over the cortex. Treatment with KA activated motor cortex, piriform cortex, olfactory bulb and hippocampus. Moreover, the relative time courses also agreed with expectations derived from the epilepsy literature. Parallel experiments, after convulsant administration using the identical paradigm, with in vivo electrophysiological recordings showed characteristic seizure-associated electrical activity. The time-course of the activity seen by electrophysiology correlates with the imaging studies and confirms the appearance of seizures following drug administration.
CONCLUSIONS: Our preliminary data suggest that BOLD MR imaging can define the initiation and anatomic propagation of seizure discharge in the rat brain. Moreover, this general approach may be applied to seizure-prone transgenic mice, elucidating the relationship between specific gene defects, cerebral anatomic abnormalities, and seizure activities.
[Supported by: NIH NS 8895, NIH NS07332, NIH DC03805, NIH HDO2274]