Chasing the lightning: Molecular epilepsy imaging with PET and SPECT

Recent studies have indicated that epilepsy may be more comprehensively characterized with the help of PET and SPECT, and these modalities could benefit the 1-2 percent of the U.S. population with the neurological disorder, according to a review published online Aug 22 in the Journal of Nuclear Medicine.

Ajay Kumar, MD, PhD, an assistant professor of pediatrics and neurology at Wayne State University of Medicine, and Harry T. Chugani, MD, chief of the division of pediatrics at Children’s Hospital of Michigan in Detroit, weighed in on PET’s potential for mapping epilepsy in the brain, specifically two types called sporadic temporal and extratemporal lobe epilepsy.

“Almost a fourth of epileptic patients do not respond to medical treatment and develop intractable seizures,” wrote Kumar and Chugani. “PET and SPECT can play a significant role in such patients by its ability to noninvasively localize epileptogenic brain regions before surgery.”

These molecular imaging techniques are not yet for first-line diagnoses or early assessment, but it has been shown to be useful for localization of epileptogenic brain regions prior to surgical treatment for patients with intractable seizures. Other beneficial applications include situations where available MR imaging is negative or if only a limited number of lesions are suspected to be epileptogenic out of several detected lesions. PET and SPECT also help when electroencephalograms show alterations that don’t match up to structural imaging. Molecular epilepsy imaging may also help provide clues regarding pathogenesis as well as a map of functional areas of the brain.

Common radiotracers used in PET epilepsy imaging include FDG, which captures metabolic changes as they relate to neuronal and synaptic brain activity. Hypometabolism specifically has been shown to be associated epileptogenic areas of the brain. The only caution with FDG PET is that it shows a large area of hypometabolism and may not be precise enough to be used to evaluate surgical margins. FDG PET has been found to be 85 to 90 percent sensitive for the evaluation of epileptic brain regions for patients with temporal lobe epilepsy. Sensitivity takes a dive, however, when using FDG PET to detect the epileptic areas involved in frontal lobe epilepsy, generally about 55 percent.

“F-18 FDG PET can provide additional information about the epileptic focus in up to two thirds of cases, affecting surgical decision making in up to 50–70 percent of cases and sometimes changing initial decisions based on MR imaging or electroencephalography,” wrote the researchers. “Further, F-18 FDG PET alone may be the basis for surgical decisions in almost 17 percent of patients.”

C-11 flumazenil is also indicated as an emerging epilepsy biomarker and works by binding to epilepsy-implicated receptors. This tracer may be better at visualizing the medial temporal lobe than FDG. A number of radioligands have also been used to target so-called translocator proteins.

For SPECT, cerebral perfusion imaging can provide key information, including changes that indicate electrical alteration and epileptiform activity.

“The most common radiotracers used for this purpose are hexamethylpropyleneamine oxime and ethyl cysteinate dimer labeled with Tc-99m,” wrote the authors. “During a seizure, the cerebral blood flow changes rapidly over time, depending on the type of seizure and its mode of propagation. Therefore, early injection of the radiotracer during the seizure is imperative to capture blood flow changes in the epileptic zone.”

SPECT assessment for focal perfusion abnormalities is possible for as many as 95 percent of presurgical patients, but not without some possibility of false-positive results. In general, though, both PET and SPECT show promise in these respective areas of epilepsy imaging, with potential for growth as part of a diversified imaging portfolio.