Abstract
Thirty percent of epilepsy patients have seizures despite best medical therapy. Continued seizures and
polypharmacy are associated with poor quality of life. While epilepsy surgery has emerged as a promising
treatment for these patients, surgical outcomes have not significantly improved over the years. These stagnant
outcomes can be attributed to poor seizure onset zone (SOZ) and epileptic network (EN) localization with
currently available tools. Epilepsy as a disease of energy metabolism has emerged as a relatively novel concept
with several studies suggesting upregulation of lactate within epileptic brain. Using patient tissue and epilepsy
models, our lab recently showed that when neurons are chronically activated, they begin to use glycolysis as a
primary means of cellular energy metabolism, thus upregulating the production of lactate. Furthermore, we
recently introduced magnetic resonance imaging (MRI) of hyperpolarized (HP) 13C pyruvate as a novel imaging
tool to spatially and temporally localize its downstream metabolic products, including lactate, in glioma and
traumatic brain injury. In this proposal we combine this novel technology with our previous findings of elevated
lactate production in epileptic tissue to explore hyperpolarized 13C MRI (hpMRI) as a means to identify epileptic
tissue. Our overarching hypothesis is that hpMRI of pyruvate will accurately identify elevated lactate production
in a rat model of focal epilepsy and in resected epileptic tissue ex vivo. In our first Aim we will use a lithium
pilocarpine rat model of temporal lobe epilepsy to explore the ability o f[1-13C]pyruvate hpMRI to identify elevated
lactate in vivo. In our second Aim, we will determine if MRS of HP [1-13C]pyruvate is able to identify elevated
lactate in resected human epileptic tissue ex vivo. These data will provide the pre-clinical evidence necessary
for a clinical trial evaluating the efficacy of 13C hpMRI as a tool to identify epileptic tissue in patients.