Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging identifies elevated lactate in epileptic tissue

Abstract

Thirty percent of epilepsy patients have seizures despite best medical therapy. While epilepsy surgery has emerged as a promising treatment option for these patients, surgical outcomes vary considerably between patients and have not significantly improved over the years. These stagnant outcomes can be attributed to poor seizure onset zone and epileptic network localization with currently available tools. Lactate production is a well-known consequence of metabolic reprogramming and biomarker in epilepsy. Detection of lactate elevations using conventional magnetic resonance spectroscopy has been extensively studied as an effective tool to non-invasively detect epileptic brain tissue. However, this method suffers from poor spatial resolution, which limits its clinical utility in presurgical resection mapping. In this study, we explore the utility of a recently developed approach, magnetic resonance spectroscopy and spectroscopic imaging of hyperpolarized [1-13C]pyruvate, to identify epileptic tissues via detection of increased lactate production. We found that this approach accurately identifies elevated lactate production in an in vitro model of chronic hyperactivity and in the gold standard mouse epilepsy model, pentylenetetrazol kindling. These data suggest that magnetic resonance spectroscopic imaging of hyperpolarized [1-13C]pyruvate has the potential to effectively and non-invasively map epileptic foci and should be further explored as a clinical tool to guide epilepsy resection surgery by identifying epileptic tissue in patients.