Volumetric glutamate imaging (GluCEST) using 7T MRI can lateralize nonlesional temporal lobe epilepsy: A preliminary study.
Peter N Hadar, Lohith G Kini, Ravi Prakash Reddy Nanga, Russell T Shinohara, Stephanie H Chen, Preya Shah, Laura E M Wisse, Mark A Elliott, Hari Hariharan, Ravinder Reddy, John A Detre, Joel M Stein, Sandhitsu Das, Kathryn A Davis
Author Information
Peter N Hadar: Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. ORCID
Lohith G Kini: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Ravi Prakash Reddy Nanga: Center for Magnetic Resonance & Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Russell T Shinohara: Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Stephanie H Chen: Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Preya Shah: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Laura E M Wisse: Penn Image Computing & Science Lab, University of Pennsylvania, Philadelphia, PA, USA.
Mark A Elliott: Center for Magnetic Resonance & Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Hari Hariharan: Center for Magnetic Resonance & Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Ravinder Reddy: Center for Magnetic Resonance & Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
John A Detre: Center for Magnetic Resonance & Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Joel M Stein: Department of Radiology, University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Sandhitsu Das: Penn Image Computing & Science Lab, University of Pennsylvania, Philadelphia, PA, USA.
Kathryn A Davis: Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
INTRODUCTION: Drug-resistant epilepsy patients show worse outcomes after resection when standard neuroimaging is nonlesional, which occurs in one-third of patients. In prior work, we employed 2-D glutamate imaging, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to lateralize seizure onset in nonlesional temporal lobe epilepsy (TLE) based on increased ipsilateral GluCEST signal in the total hippocampus and hippocampal head. We present a significant advancement to single-slice GluCEST imaging, allowing for three-dimensional analysis of brain glutamate networks. METHODS: The study population consisted of four MRI-negative, nonlesional TLE patients (two male, two female) with electrographically identified left temporal onset seizures. Imaging was conducted on a Siemens 7T MRI scanner using the CEST method for glutamate, while the advanced normalization tools (ANTs) pipeline and the Automated Segmentation of the Hippocampal Subfields (ASHS) method were employed for image analysis. RESULTS: Volumetric GluCEST imaging was validated in four nonlesional TLE patients showing increased glutamate lateralized to the hippocampus of seizure onset (p = .048, with a difference among ipsilateral to contralateral GluCEST signal percentage ranging from -0.05 to 1.37), as well as increased GluCEST signal in the ipsilateral subiculum (p = .034, with a difference among ipsilateral to contralateral GluCEST signal ranging from 0.13 to 1.57). CONCLUSIONS: The ability of 3-D, volumetric GluCEST to localize seizure onset down to the hippocampal subfield in nonlesional TLE is an improvement upon our previous 2-D, single-slice GluCEST method. Eventually, we hope to expand volumetric GluCEST to whole-brain glutamate imaging, thus enabling noninvasive analysis of glutamate networks in epilepsy and potentially leading to improved clinical outcomes.
