Research ArticleEpilepsy

Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy

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Science Translational Medicine  14 Oct 2015:
Vol. 7, Issue 309, pp. 309ra161
DOI: 10.1126/scitranslmed.aaa7095

Toward visualizing the focus

Many seizures, especially those that originate in the brain’s temporal lobe, start at a single spot in the brain. If drugs fail, excision of this region can often provide relief from seizures. A new imaging method that harnesses the power of a 7-T magnet shows promise in locating hard-to-find epileptic foci by visualizing the neurotransmitter glutamate.

In a pilot study, the authors used glutamate chemical exchange saturation transfer (GluCEST), a very high resolution magnetic resonance imaging contrast method, to measure how much glutamate was in the hippocampi of four patients with epilepsy. Glutamate is elevated in epileptic foci. The amount of glutamate was clearly higher in one of the hippocampi in all four patients, and confirmatory methods (electroencephalography or magnetic resonance spectra) verified independently that the hippocampus with the elevated glutamate was located in the same hemisphere as the epileptic focus.

Although the authors have only taken a first step toward noninvasively finding epileptic foci, their demonstration that GluCEST can localize small brain hot spots of high glutamate is promising. This approach can potentially allow a higher rate of successful surgeries in this difficult disease.


When neuroimaging reveals a brain lesion, drug-resistant epilepsy patients show better outcomes after resective surgery than do the one-third of drug-resistant epilepsy patients who have normal brain magnetic resonance imaging (MRI). We applied a glutamate imaging method, GluCEST (glutamate chemical exchange saturation transfer), to patients with nonlesional temporal lobe epilepsy based on conventional MRI. GluCEST correctly lateralized the temporal lobe seizure focus on visual and quantitative analyses in all patients. MR spectra, available for a subset of patients and controls, corroborated the GluCEST findings. Hippocampal volumes were not significantly different between hemispheres. GluCEST allowed high-resolution functional imaging of brain glutamate and has potential to identify the epileptic focus in patients previously deemed nonlesional. This method may lead to improved clinical outcomes for temporal lobe epilepsy as well as other localization-related epilepsies.

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