Lateralization of temporal lobe epileptic foci with automated chemical exchange saturation transfer measurements at 3 Tesla

Background: Magnetic Resonance Imaging (MRI) is an indispensable tool for the diagnosis of temporal lobe epilepsy (TLE). However, about 30% of TLE patients show no lesion on structural MRI (sMRI-negative), posing a significant challenge for presurgical evaluation. This study aimed to investigate whether chemical exchange saturation transfer (CEST) MRI at 3 Tesla can lateralize the epileptic focus of TLE and study the metabolic contributors to the CEST signal measured. Methods: Forty TLE subjects (16 males and 24 females) were included in this study. An automated data analysis pipeline was established, including segmentation of the hippocampus and amygdala (HA), calculation of four CEST metrics and quantitative relaxation times (T₁ and T₂), and construction of prediction models by logistic regression. Furthermore, a modified two-stage Bloch–McConnell fitting method was developed to investigate the molecular imaging mechanism of 3 T CEST in identifying epileptic foci of TLE. Findings: The mean CEST ratio (CESTR) metric within 2.25–3.25 ppm in the HA was the most powerful index in predicting seizure laterality, with an area under the receiver-operating characteristic curve (AUC) of 0.84. And, the combination of T₂ and CESTR further increased the AUC to 0.92. Amine and guanidinium moieties were the two leading contributors to the CEST contrast between the epileptogenic HA and the normal HA. Interpretation: CEST at 3 Tesla is a powerful modality that can predict seizure laterality with high accuracy. This study can potentially facilitate the clinical translation of CEST MRI in identifying the epileptic foci of TLE or other localization-related epilepsies. Funding: National Natural Science Foundation of China, Science Technology Department of Zhejiang Province, and Zhejiang University.