Penn Epilepsy Center, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Brain Behav. 2021 Aug;11(8):e02134. doi: 10.1002/brb3.2134. Epub 2021 Jul 13.
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.
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.
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).
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.
当标准神经影像学无病变时，耐药性癫痫患者的切除术后结果更差，这种情况发生在三分之一的患者中。在之前的工作中，我们使用二维谷氨酸成像（Glutamate Chemical Exchange Saturation Transfer，GluCEST），根据总海马体和海马体头部的同侧 GluCEST 信号增加，来对非病变性颞叶癫痫（temporal lobe epilepsy，TLE）患者的癫痫发作起始进行侧化定位。我们提出了 GluCEST 成像的一项重要进展，允许对脑谷氨酸网络进行三维分析。
该研究人群包括 4 名 MRI 阴性、非病变性 TLE 患者（2 名男性，2 名女性），他们的脑电图显示左侧颞叶起始性癫痫发作。成像在西门子 7T MRI 扫描仪上进行，使用谷氨酸的 CEST 方法，同时使用先进的归一化工具（Advanced Normalization Tools，ANTs）流水线和自动海马亚区分割（Automated Segmentation of the Hippocampal Subfields，ASHS）方法进行图像分析。
在 4 名非病变性 TLE 患者中，对容积 GluCEST 成像进行了验证，显示谷氨酸向癫痫发作起始的海马体侧化（p=0.048，同侧与对侧 GluCEST 信号百分比差异范围为-0.05 至 1.37），以及同侧下托（subiculum）的 GluCEST 信号增加（p=0.034，同侧与对侧 GluCEST 信号差异范围为 0.13 至 1.57）。
3D 容积 GluCEST 能够将癫痫发作起始定位到非病变性 TLE 的海马亚区，这是我们之前的 2D 单切片 GluCEST 方法的改进。最终，我们希望将容积 GluCEST 扩展到全脑谷氨酸成像，从而能够对癫痫中的谷氨酸网络进行非侵入性分析，并可能导致改善临床结果。
