Abstracts

Rationale: Epilepsy is a common neurologic disorder that affects 2.2 million Americans and 65 million people worldwide. Prior work has shown that glutamate plays a key role in the initiation and maintenance of seizures (Olney 1974; Riban 2002). Subsequent intracranial electrocorticography and microdialysis studies suggest that glutamate levels are increased both ictally and interictally. The magnitude of glutamate elevation is more robust in temporal lobe versus neocortical epilepsy (TLE) patients and also seems to correlate with frequency and duration of seizure activity (Cavus 2005; Kanoamori 2011). Thus, relative differences in glutamate concentration have the potential to help localize areas of epileptogenicity. Glutamate Chemical Exchange Saturation Transfer (GluCEST) is a noninvasive, metabolic imaging technique that quantifies glutamate. The objective of this study was to apply this novel imaging technique to compare epileptic networks in lesional and nonlesional refractory TLE patients.Methods: Seven patients undergoing presurgical evaluation for drug resistant TLE were recruited from the Penn Epilepsy Center: 4 nonlesional (2 right, 2 left onset) and 3 lesional (1 right, 2 left onset). Eleven age-matched controls were also recruited. GluCEST MRI was acquired on a 7.0T MRI scanner with a 32-channel phased-array head coil. The GluCEST imaging parameters were: slice thickness = 5 mm, field of view read = 200 mm, field of view phase = 162.5 mm, matrix size = 208 × 256, GRE read out TR = 6.2 ms, TE = 3 ms, number of averages = 2, shot TR = 10000 ms, shots per slice = 2, with one saturation pulse at a B1rms of 3.06 μT with 800 ms duration. Raw CEST images were acquired at varying saturation offset frequencies from ±1.8 to ±4.2 ppm (relative to water resonance) with a step size of ±0.3 ppm. The B0 and B1 corrected GluCEST contrasts were then averaged within expertly drawn regions-of-interest (ROIs) in the bilateral hippocampi. Two-sample t-test for means was performed on control and epilepsy patients for the lesional and nonlesional groups (1-tailed).Results: In the four nonlesional TLE patients, GluCEST concentration was increased in the epileptogenic hippocampus (p=0.011) when compared to controls. Conversely, in the three lesional TLE patients, GluCEST concentration was decreased in the epileptogenic hippocampus (p=0.038) when compared to controls. All three lesional patients underwent surgery (2 anterior temporal lobectomy, 1 laser ablation), and pathology confirmed mesial temporal sclerosis.Conclusions: GluCEST is a novel imaging technique that has the potential to lateralize epileptic foci. Our results suggest that there is an underlying difference in glutamate concentration between the lesional and nonlesional hippocampus in refractory TLE patients. We are currently continuing further study with increased sample size as well as whole brain GluCEST imaging.