New neuroimaging technique finds unknown epileptic seizure sites

John Murphy, MDLinx | November 16, 2015

Researchers reported a new imaging technique that can trace the location of epileptic seizures that conventional MRI or PET imaging cannot detect. This innovation has the potential to increase the clinical treatment options available for certain patients with epilepsy. Their study appeared October 14, 2015 in the journal Science Translational Medicine

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GluCEST imaging reveals epileptic seizure sites

GluCEST imaging reveals increased glutamate levels in the hippocampus (orange), which indicates areas where epileptic seizures originate. (Image: National Institute of Biomedical Imaging and Bioengineering)

Conventional imaging procedures allow surgeons to identify and remove the brain lesions that cause epileptic seizures. But about one third of patients with drug-resistant epilepsy show no identifiable abnormality on conventional imaging studies, which means they have fewer surgical options. Now, researchers have demonstrated a method of advanced noninvasive functional imaging that can recognize the neurotransmitter glutamate, which appears to be the culprit behind the most common form of medication-resistant epilepsy.

Glutamate is involved in neuronal signaling, and rapidly dissipates after signaling. In patients with epilepsy, stroke, and possibly ALS, the glutamate doesn’t clear, which leaves the neuron overwhelmed with messages, and in a toxic state of prolonged excitation. 

“We theorized that if we could develop a technique which allows us to track the path of, and make noninvasive measurements of, glutamate in the brain, we would be able to better identify the brain lesions and epileptic foci that current methods miss,” said senior author Ravinder Reddy, PhD, Professor of Radiology and Director of the Center for Magnetic Resonance and Optical Imaging at the University of Pennsylvania’s Perelman School of Medicine, in Philadelphia, PA.

Dr. Reddy and his colleagues developed a specialized MRI technique—glutamate chemical exchange saturation transfer (GluCEST)—that takes advantage of the unique chemical properties of glutamate. In this technique, water molecules that surround the neurotransmitter can be visualized at very high resolution. The increased signal from the surrounding water molecules indicates increased levels of glutamate, which identifies the epileptic focus.

In 4 patients with drug-resistant epilepsy, GluCEST imaging correctly detected consistently higher levels of glutamate in the side of the hippocampus where the epileptic seizures originated. The researchers confirmed their findings (using electroencephalography and magnetic resonance spectra) that the hippocampus with the elevated glutamate was located in the same hemisphere as the epileptic focus. In 11 healthy individuals tested for comparison, the GluCEST signal showed no lateralization to any particular side of the hippocampus.

“The demonstration that GluCEST can localize hot spots of increased glutamate is a promising step towards improved treatment,” said the study’s lead author Kathryn Davis, MD, Assistant Professor of Neurology at the University of Pennsylvania’s Perelman School of Medicine. “Finding the epileptic foci in a specific brain region gives clinicians critical information to guide targeted therapies that have the potential to control seizures in patients that currently do not have treatment options.”

The imaging technique could give drug-resistant epilepsy patients the opportunity for improved clinical outcomes with an expanded number treatments, such as surgery, laser ablation therapy, or neurostimulation, the authors wrote.

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