Share:
Share this content in WeChat
X
Clinical Article
GluCEST imaging and structural changes in bilateral thalami of epileptic children with negative conventional MRI
WANG Wen  XIA Shuyuan  LI Xianglin  XU Donghao  LIU Quanyuan  REN Qingfa  YIN Zhijie  WANG Jing  LIU Xinkai 

DOI:10.12015/issn.1674-8034.2026.07.001.


[Abstract] Objective The glutamate-weighted chemical exchange saturation transfer (GluCEST) imaging technique was used to evaluate the changes of glutamate (Glu) in the thalamus of children with negative MRI - confirmed epilepsy. Furthermore, the volume changes of the subregions of the thalamus in these children were explored, and the correlation between the Glu changes measured by GluCEST and the volume of the thalamic subregions was analyzed.Materials and Methods A total of 73 pediatric patients diagnosed with epilepsy were prospectively enrolled between January 2024 and May 2026 at the Department of Pediatric Neurology, Binzhou Medical University Hospital. They were divided into the focal epilepsy (FE) group with 37 cases and the generalized epilepsy (GE) group with 36 cases. Thirty-six healthy control (HCs) subjects were recruited. The brain magnetic resonance images of the three groups were collected to exclude data with brain diseases. Those meeting the requirements were subjected to three-dimensional T1-weighted magnetization prepared rapid gradient echo (MPRAGE) imaging and GluCEST imaging. The GluCEST images were processed using Matlab software to obtain the asymmetric magnetization rate (MTRasym) value of the thalamus region, representing the relative Glu concentration value of this area; the MPRAGE images were automatically segmented using FreeSurfer to obtain the volume of the thalamic subregions. SPSS was used to compare the MTRasym values of the left and right thalamus in the three groups, and to compare the thalamic MTRasym values and subregion volumes between the GE group and the HCs group, as well as between the FE group and the HCs group.Results The MTRasym value of the ipsilateral thalamus in the focal epilepsy (FE) group was significantly higher than that of the contralateral thalamus, with a statistically significant difference (t = 3.252, P = 0.002). In the generalized epilepsy (GE) group, both the left (Z = -4.944, P < 0.001) and right (t = 4.816, P < 0.001) thalamic MTRasym values were significantly elevated compared to those in the healthy control (HC) group. Similarly, both the ipsilateral (t = 4.547, P < 0.001) and contralateral (t = 3.293, P = 0.002) thalamic MTRasym values in the FE group were significantly higher than those in the HC group. Regarding thalamic subregion volumes, the volume of the right medial nucleus in the GE group was significantly smaller than that in the HC group (t = -2.667, P = 0.009); however, no significant differences were observed between the FE group and the HC group in any thalamic subregion (P > 0.05). Furthermore, no significant correlation was found between thalamic MTRasym values and the volumes of thalamic subregions in either the GE or FE groups (P > 0.05).Conclusions This study employed GluCEST imaging in conjunction with structural MRI to investigate glutamate concentration and volumetric alterations in the thalamus among children with epilepsy and negative conventional MRI findings. Furthermore, the correlation between MTRasym values and the volumes of specific thalamic subregions was examined. It is helpful to understand the neuro-metabolic differences of different types of epilepsy, and it opens up a new perspective for the diagnosis, treatment and prognosis of children with epilepsy. GluCEST technology is expected to provide a new, non-invasive imaging tool for exploring the pathophysiological mechanism of childhood epilepsy.
[Keywords] epilepsy;Children;glutamate chemical exchange saturation transfer;magnetic resonance imaging;thalamus;glutamate

WANG Wen1   XIA Shuyuan1   LI Xianglin2   XU Donghao3   LIU Quanyuan1   REN Qingfa1   YIN Zhijie1   WANG Jing1   LIU Xinkai1*  

1 Department of Radiology, Binzhou Medical University Hospital, Binzhou 256600, China

2 School of Medical Imaging, Binzhou Medical University, Yantai 264003, China

3 Department of Radiology, Central Hospital of Shengli Oilfield, Dongying 257100, China

Corresponding author: LIU X K, E-mail: 104158000@qq.com

Conflicts of interest   None.

Received  2026-01-21
Accepted  2026-04-21
DOI: 10.12015/issn.1674-8034.2026.07.001
DOI:10.12015/issn.1674-8034.2026.07.001.

[1]
RINEY K, BOGACZ A, SOMERVILLE E, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions[J]. Epilepsia, 2022, 63(6): 1443-1474. DOI: 10.1111/epi.17240.
[2]
COLLABORATORS G B D E. Global, regional, and national burden of epilepsy, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J/OL]. Lancet Public Health, 2025, 10(3): e203-e227 [2026-01-06]. https://doi.org/10.1016/S2468-2667(24)00302-5. DOI: 10.1016/S2468-2667(24)00302-5.
[3]
ASADI-POOYA A A, BRIGO F, LATTANZI S, et al. Adult epilepsy[J]. Lancet, 2023, 402(10399): 412-424. DOI: 10.1016/S0140-6736(23)01048-6.
[4]
ROZENSZTRAUCH A, KOLTUNIUK A. The Quality of Life of Children with Epilepsy and the Impact of the Disease on the Family Functioning[J/OL]. Int J Environ Res Public Health, 2022, 19(4): 2277 [2026-01-06]. https://doi.org/10.3390/ijerph19042277. DOI: 10.3390/ijerph19042277.
[5]
BEGHI E. The Epidemiology of Epilepsy[J]. Neuroepidemiology, 2020, 54(2): 185-191. DOI: 10.1159/000503831.
[6]
YILDIZ MINIKSAR D, KILIC B, KILIC M, et al. Evaluation of suicide probability in children and adolescents with epilepsy[J/OL]. Pediatr Int, 2022, 64(1): e15130[2026-01-06]. https://doi.org/10.1111/ped.15130. DOI: 10.1111/ped.15130.
[7]
CHEN T S, HUANG T H, LAI M C, et al. The Role of Glutamate Receptors in Epilepsy[J/OL]. Biomedicines, 2023, 11(3): 783 [2026-01-06]. https://doi.org/10.3390/biomedicines11030783. DOI: 10.3390/biomedicines11030783.
[8]
ALCOREZA O B, PATEL D C, TEWARI B P, et al. Dysregulation of Ambient Glutamate and Glutamate Receptors in Epilepsy: An Astrocytic Perspective[J/OL]. Front Neurol, 2021, 12: 652159 [2026-01-06]. https://doi.org/10.3389/fneur.2021.652159. DOI: 10.3389/fneur.2021.652159.
[9]
NEGRETE-DIAZ J V, FALCON-MOYA R, RODRIGUEZ-MORENO A. Kainate receptors: from synaptic activity to disease[J]. FEBS J, 2022, 289(17): 5074-5088. DOI: 10.1111/febs.16081.
[10]
KANTROWITZ J T, DONG Z, MILAK M S, et al. Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder[J/OL]. Transl Psychiatry, 2021, 11(1): 419 [2026-01-06]. https://doi.org/10.1038/s41398-021-01541-1. DOI: 10.1038/s41398-021-01541-1.
[11]
PEPIN J, DE LONGPREZ L, TROVERO F, et al. Complementarity of gluCEST and (1)H-MRS for the study of mouse models of Huntington's disease[J/OL]. NMR Biomed, 2020, 33(7): e4301[2026-01-06]. https://doi.org/10.1002/nbm.4301. DOI: 10.1002/nbm.4301.
[12]
CEMBER A T J, DECK B L, KELKAR A, et al. Glutamate-Weighted Magnetic Resonance Imaging (GluCEST) Detects Effects of Transcranial Magnetic Stimulation to the Motor Cortex[J/OL]. Neuroimage, 2022, 256: 119191 [2026-01-06]. https://doi.org/10.1016/j.neuroimage.2022.119191. DOI: 10.1016/j.neuroimage.2022.119191.
[13]
CAI K, HARIS M, SINGH A, et al. Magnetic resonance imaging of glutamate[J]. Nat Med, 2012, 18(2): 302-306. DOI: 10.1038/nm.2615.
[14]
REN Q, WAN B, LUO X, et al. Glutamate alterations in the premature infant brain during different gestational ages with glutamate chemical exchange saturation transfer imaging: a pilot study[J]. Eur Radiol, 2023, 33(6): 4214-4222. DOI: 10.1007/s00330-022-09374-2.
[15]
WANG K, WEN Q, WU D, et al. Lateralization of temporal lobe epileptic foci with automated chemical exchange saturation transfer measurements at 3 Tesla[J/OL]. EBioMedicine, 2023, 89: 104460 [2026-01-06]. https://doi.org/10.1016/j.ebiom.2023.104460. DOI: 10.1016/j.ebiom.2023.104460.
[16]
DUAN X L, LIU Z Y, YANG C, et al. Combined non-invasive lateralization of hippocampal head glutamate excitotoxicity and structural atrophy for refractory temporal lobe epilepsy based on multimodal MRI[J]. Chin J Magn Reson Imaging, 2025, 16(12): 52-58. DOI: 10.12015/issn.1674-8034.2025.12.008.
[17]
XU D, REN Q, LIU Q, et al. Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School‐Aged Children With MRI‐Negative Epilepsy: A Preliminary Study[J]. J Magn Reson Imaging, 2024, 61(3): 1258-1268. DOI: 10.1002/jmri.29514.
[18]
WU T Q, KABOODVAND N, MCGINN R J, et al. Multisite thalamic recordings to characterize seizure propagation in the human brain[J]. Brain, 2023, 146(7): 2792-2802. DOI: 10.1093/brain/awad121.
[19]
MARTIN-LOPEZ D, JIMENEZ-JIMENEZ D, CABANES-MARTINEZ L, et al. The Role of Thalamus Versus Cortex in Epilepsy: Evidence from Human Ictal Centromedian Recordings in Patients Assessed for Deep Brain Stimulation[J/OL]. Int J Neural Syst, 2017, 27(7): 1750010 [2026-01-06]. https://doi.org/10.1142/S0129065717500101. DOI: 10.1142/S0129065717500101.
[20]
LUCAS A, MOUCHTARIS S, TRANQUILLE A, et al. Mapping hippocampal and thalamic atrophy in epilepsy: A 7-T magnetic resonance imaging study[J]. Epilepsia, 2024, 65(4): 1092-1106. DOI: 10.1111/epi.17908.
[21]
TAKADO Y, TAKUWA H, SAMPEI K, et al. MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice[J]. J Cereb Blood Flow Metab, 2021, 42(1): 197-212. DOI: 10.1177/0271678X211045449.
[22]
BENICZKY S, TRINKA E, WIRRELL E, et al. Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy[J]. Epilepsia, 2025, 66(6): 1804-1823. DOI: 10.1111/epi.18338.
[23]
LIU R, ZHANG H, QIAN Y, et al. Frequency‐stabilized chemical exchange saturation transfer imaging with real‐time free‐induction‐decay readout[J]. Magn Reson Med, 2020, 85(3): 1322-1334. DOI: 10.1002/mrm.28513.
[24]
WEELAND C J, VRIEND C, VAN DER WERF Y, et al. Thalamic Subregions and Obsessive-Compulsive Symptoms in 2, 500 Children From the General Population[J]. J Am Acad Child Psy, 2022, 61(2): 321-330. DOI: 10.1016/j.jaac.2021.05.024.
[25]
CEMBER A T J, NANGA R P R, REDDY R. Glutamate‐weighted CEST (gluCEST) imaging for mapping neurometabolism: An update on the state of the art and emerging findings from in vivo applications[J/OL]. NMR in Biomedicine, 2022, 36(6): e4780[2026-01-06]. https://doi.org/10.1002/nbm.4780. DOI: 10.1002/nbm.4780.
[26]
HERSHEY N D, POPOV P, OLIVER N M, et al. Detection of Neuronal Glutamate in Brain Extracellular Space In Vivo Using Microdialysis and Metabolic Labeling with Glutamine[J]. ACS Chem Neurosci, 2025, 16(17): 3398-3409. DOI: 10.1021/acschemneuro.5c00518.
[27]
LI H, LUO X, QI K, et al. Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI to Evaluate the Rapid Antidepressant Effects of Ketamine in the Hippocampus of Rat Depression Model[J]. J Magn Reson Imaging, 2023, 59(4): 1373-1381. DOI: 10.1002/jmri.28921.
[28]
SONI N D, SWAIN A, JUUL H, et al. Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI[J]. Alzheimer's & Dementia, 2024, 20(10): 7124-7137. DOI: 10.1002/alz.14190.
[29]
LIU Y, DONG L R, HUANG S X, et al. Application of Magnetic Resonance Chemical Exchange Saturation Transfer Glutamate Imaging in Schizophrenia[J]. Radiol Prac, 2023, 38(7): 830-834. DOI: 10.13609/j.cnki.1000-0313.2023.07.004.
[30]
STUDTMANN C, LADISLAV M, TOPOLSKI M A, et al. NaV1.1 haploinsufficiency impairs glutamatergic and GABAergic neuron function in the thalamus[J/OL]. Neurobiology of Disease, 2022, 167: 105672 [2026-01-06]. https://doi.org/10.1016/j.nbd.2022.105672. DOI: 10.1016/j.nbd.2022.105672.
[31]
VEZZANI A, RAVIZZA T, BEDNER P, et al. Astrocytes in the initiation and progression of epilepsy[J]. Nat Rev Neurol, 2022, 18(12): 707-722. DOI: 10.1038/s41582-022-00727-5.
[32]
MOHANTY D, HOUCK K M, TRANDAFIR C, et al. Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults[J]. JNS-Pediatrics, 2024, 34(1): 40-48. DOI: 10.3171/2024.2.PEDS23531.
[33]
GHEISARI F, SHAMMAS A, MARIE E, et al. Prognostic Values of Thalamic Metabolic Abnormalities in Children with Epilepsy[J/OL]. Diagnostics, 2025, 15(15): 1865 [2026-01-06]. https://doi.org/10.3390/diagnostics15151865. DOI: 10.3390/diagnostics15151865.
[34]
LU D, JI Y, SUNDARAM P, et al. Alkaline brain pH shift in rodent lithium-pilocarpine model of epilepsy with chronic seizures[J/OL]. Brain Res, 2021, 1758: 147345 [2026-01-06]. https://doi.org/10.1016/j.brainres.2021.147345. DOI: 10.1016/j.brainres.2021.147345.
[35]
HE X, CHAITANYA G, ASMA B, et al. Disrupted basal ganglia–thalamocortical loops in focal to bilateral tonic-clonic seizures[J]. Brain, 2020, 143(1): 175-190. DOI: 10.1093/brain/awz361.
[36]
LINDQUIST B E, TIMBIE C, VOSKOBIYNYK Y, et al. Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets[J/OL]. Neurobiol Dis, 2023, 181: 106094 [2026-01-06]. https://doi.org/10.1016/j.nbd.2023.106094. DOI: 10.1016/j.nbd.2023.106094.
[37]
SANTUCCI F, JIMENEZ-MARIN A, GABRIELLI A, et al. Partial correlation as a tool for mapping functional-structural correspondence in human brain connectivity[J]. Netw Neurosci, 2025, 9(3): 1065-1086. DOI: 10.1162/NETN.a.22.
[38]
BERNASCONI A. Magnetic resonance spectroscopy and imaging of the thalamus in idiopathic generalized epilepsy[J]. Brain, 2003, 126(11): 2447-2454. DOI: 10.1093/brain/awg249.
[39]
ZANG Y F, WANG Z, ZHANG Z, et al. Impairments of Thalamic Nuclei in Idiopathic Generalized Epilepsy Revealed by a Study Combining Morphological and Functional Connectivity MRI[J/OL]. PLoS ONE, 2012, 7(7): e39701[2026-01-06]. https://doi.org/10.1371/journal.pone.0039701. DOI: 10.1371/journal.pone.0039701.
[40]
CHEN Y, FALLON N, KREILKAMP B A K, et al. Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy[J]. Hum Brain Mapp, 2021, 42(17): 5648-5664. DOI: 10.1002/hbm.25644.
[41]
WANG Z, LARIVIèRE S, XU Q, et al. Community-informed connectomics of the thalamocortical system in generalized epilepsy[J/OL]. Neurology, 2019, 93(11): e1112-e1122 [2026-01-06]. https://doi.org/10.1212/WNL.0000000000008096. DOI: 10.1212/WNL.0000000000008096.
[42]
TOWNE J M, LAMI V, BARRON D S, et al. Neuroimaging signatures of mesial temporal lobe epilepsy: A coordinate-based meta-analysis of structural and resting-state functional imaging literature[J/OL]. NeuroImage-Clin, 2025, 48: 103908 [2026-01-06]. https://doi.org/10.1016/j.nicl.2025.103908. DOI: 10.1016/j.nicl.2025.103908.
[43]
WHELAN C D, ALTMANN A, BOTIA J A, et al. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study[J]. Brain, 2018, 141(2): 391-408. DOI: 10.1093/brain/awx341.
[44]
LUCAS A, NANGA R P R, HADAR P, et al. Mapping hippocampal glutamate in mesial temporal lobe epilepsy with glutamate weighted CEST (GluCEST) imaging[J]. Hum Brain Mapp, 2022, 44(2): 549-558. DOI: 10.1002/hbm.26083.
[45]
ZHANG X Y. The Effects of Different Activated Microglia on Potential Epileptic Suscptibility Metabotropic Glutamate Receptors[D]. Changchun: Jilin University, 2020. DOI: 10.27162/d.cnki.gjlin.2020.000537.
[46]
ELGER C E, HOPPE C. Diagnostic challenges in epilepsy: seizure under-reporting and seizure detection[J]. Lancet Neurol, 2018, 17(3): 279-288. DOI: 10.1016/S1474-4422(18)30038-3.

PREV Advances in the application of arterial spin labeling MRI in placental perfusion
NEXT Meta-analysis of gray matter volume and resting-state functional connectivity in type 2 diabetes-related cognitive impairment
  



Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn