Share:
Share this content in WeChat
X
Clinical Article
Non-invasive lateralization of refractory temporal lobe epilepsy using combined hippocampal head glutamate excitotoxicity and structural atrophy based on multimodal MRI
DUAN Xiaoling  LIU Zhenye  YANG Chao  WANG Xiaoyang  LIAO Yingyong  LIN Qiao  XU Shangwen  LI Hui 

DOI:10.12015/issn.1674-8034.2025.12.008.


[Abstract] Objective To quantitatively assess metabolic ratios and hippocampal volumetric parameters in patients with drug-refractory temporal lobe epilepsy (TLE) using proton magnetic resonance spectroscopy (¹H-MRS) and artificial intelligence (AI)-based automated brain segmentation, and to evaluate their diagnostic efficacy in lateralizing the epileptogenic focus.Materials and Methods A total of 27 TLE patients and 27 healthy controls underwent three-dimensional T1-weighted imaging (3D-T1WI) and multi-voxel ¹H-MRS on a 3.0 T MRI scanner. Hippocampal volume ratio (defined as the percentage of hippocampal volume relative to total brain volume) was measured bilaterally in both groups using United Imaging Intelligence brain segmentation technology. Glutamate-to-creatine ratio (Glu/Cr) and N-acetylaspartate-to-creatine ratio (NAA/Cr) were measured in the bilateral hippocampal head, bodyand tail.Results ¹H-MRS: The Glu/Cr ratio in the affected hippocampal head of TLE patients was significantly higher than that in the contralateral side (P = 0.012) and the control group (P < 0.001). No significant differences in NAA/Cr ratios were found between the affected and contralateral hippocampal subregions (P > 0.05). Volumetry: The hippocampal volume ratio on the affected side was significantly lower than that on the contralateral side (P = 0.033) and in the control group (P < 0.001). Diagnostic performance [receiver operating characteristic (ROC) analysis, hippocampal head Glu/Cr ratio for lateralization: Sensitivity 88.9%, Specificity 70.4%, area under the curve (AUC) = 0.859]. Hippocampal volume ratio for lateralization: Specificity 88.9%, Sensitivity 70.4% (AUC = 0.808). Combined diagnosis (Glu/Cr + volume ratio): Sensitivity 81.5%, Specificity 96.3% (AUC = 0.941).Conclusions This study confirms the presence of specific glutamate excitotoxicity (↑Glu/Cr) and structural atrophy in the affected hippocampal head of TLE patients. The combined application of hippocampal head Glu/Cr ratio (high sensitivity) and hippocampal volume ratio (high specificity) significantly enhances the efficacy for lateralizing the epileptogenic focus (AUC = 0.941), outperforming either single metric. This multimodal MRI biomarker combination provides a high-value tool for non-invasive pre-surgical localization in drug-refractory TLE.
[Keywords] drug-resistant epilepsy;magnetic resonance imaging;proton magnetic resonance spectroscopy;intelligence brain segmentation technology;hippocampal volume ratio;hippocampus

DUAN Xiaoling1, 2, 3   LIU Zhenye1   YANG Chao2   WANG Xiaoyang2   LIAO Yingyong2   LIN Qiao4   XU Shangwen2   LI Hui1, 2, 3*  

1 Department of Diagnostic Radiology, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 350025, China

2 Department of Diagnostic Radiology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350025, China

3 Department of Diagnostic Radiology, Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital), Fuzhou 350025, China

4 Department of Neurosurgery, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350025, China

Corresponding author: LI H, E-mail: 582788441@qq.com

Conflicts of interest   None.

Received  2025-08-11
Accepted  2025-10-13
DOI: 10.12015/issn.1674-8034.2025.12.008
DOI:10.12015/issn.1674-8034.2025.12.008.

[1]
USUI K, TERADA K, INOUE Y. Diagnostic approach for studying epileptic seizure[J]. Rinsho Shinkeigaku, 2012, 52(11): 857-860. DOI: 10.5692/clinicalneurol.52.857.
[2]
MARTINEZ B, PEPLOW P V. MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy[J]. Neural Regen Res, 2023, 18(4): 716-726. DOI: 10.4103/1673-5374.354510.
[3]
SINGH J, EBERSOLE J S, BRINKMANN B H. From theory to practical fundamentals of electroencephalographic source imaging in localizing the epileptogenic zone[J]. Epilepsia, 2022, 63(10): 2476-2490. DOI: 10.1111/epi.17361.
[4]
ARENDS J B A M. Movement-based seizure detection[J]. Epilepsia, 2018, 59Suppl 1: 30-35. DOI: 10.1111/epi.14053.
[5]
ZHOU D J, GUMENYUK V, TARASCHENKO O, et al. Visualization of the Spatiotemporal Propagation of Interictal Spikes in Temporal Lobe Epilepsy: A MEG Pilot Study[J]. Brain Topogr, 2024, 37(1): 116-125. DOI: 10.1007/s10548-023-01017-z.
[6]
MIDDLEBROOKS E H, HOEF L VER, SZAFLARSKI J P. Neuroimaging in Epilepsy[J/OL]. Curr Neurol Neurosci Rep, 2017, 17(4): 32 [2025-08-11]. https://doi.org/10.1007/s11910-017-0746-x. DOI: 10.1007/s11910-017-0746-x.
[7]
QU B, TAN H, XIAO M, et al. Evaluation of the diagnostic utility on 1.5T and 3.0T 1H magnetic resonance spectroscopy for temporal lobe epilepsy[J/OL]. BMC Med Imaging, 2023, 23(1): 185 [2025-08-11]. https://doi.org/10.1186/s12880-023-01136-w. DOI: 10.1186/s12880-023-01136-w.
[8]
THEODORE W H, GAILLARD W D, DE CARLI C, et al. Hippocampal volume and glucose metabolism in temporal lobe epileptic foci[J]. Epilepsia, 2001, 42(1): 130-132. DOI: 10.1046/j.1528-1157.2001.080874.x.
[9]
SONG L G, XU S W. The Value of Automatic Hippocampal Volumetry in Mesial Temporal Lobe Epilepsy[J]. Fujian Medical Journal, 2025, 47(3): 1-4. DOI: 10.20148/j.fmj2025.03.001.
[10]
MENZLER K, HAMER H M, MROSS P, et al. Validation of automatic MRI hippocampal subfield segmentation by histopathological evaluation in patients with temporal lobe epilepsy[J]. Seizure, 2021, 87: 94-102. DOI: 10.1016/j.seizure.2021.03.007.
[11]
FISHER R S, CROSS J H, D'SOUZA C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types[J]. Epilepsia, 2017, 58(4): 531-542. DOI: 10.1111/epi.13671.
[12]
ZHU H, ADELI E, SHI F; Alzheimer's Disease Neuroimaging Initiative. FCN Based Label Correction for Multi-Atlas Guided Organ Segmentation[J]. Neuroinformatics, 2020, 18(2): 319-331. DOI: 10.1007/s12021-019-09448-5.
[13]
BLÜMCKE I, ARONICA E, MIYATA H, et al. International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods[J]. Epilepsia, 2016, 57(3): 348-358. DOI: 10.1111/epi.13319.
[14]
PIMENTEL-SILVA L R, CASSEB R F, CORDEIRO M M, et al. Interactions between in vivo neuronal-glial markers, side of hippocampal sclerosis, and pharmacoresponse in temporal lobe epilepsy[J]. Epilepsia, 2020, 61(5): 1008-1018. DOI: 10.1111/epi.16509.
[15]
ZHAO T, CUI X, ZHANG X, et al. Hippocampal sclerosis: A review on current research status and its mechanisms[J/OL]. Ageing Res Rev, 2025, 108: 102716 [2025-08-11]. https://doi.org/10.1016/j.arr.2025.102716. DOI: 10.1016/j.arr.2025.102716.
[16]
SOBSTYL M, KOWALSKA M, KONOPKO M, et al. Deep brain stimulation of the subiculum in the treatment for refractory temporal lobe epilepsy due to unilateral mesial temporal lobe sclerosis[J/OL]. Epilepsy Behav Rep, 2024, 27: 100677 [2025-08-11]. https://doi.org/10.1016/j.ebr.2024.100677. DOI: 10.1016/j.ebr.2024.100677.
[17]
DE STEFANO F A, MORELL A A, SMITH G, et al. Unique magnetic resonance spectroscopy profile of intracranial meningiomas compared to gliomas: a systematic review[J]. Acta Neurol Belg, 2023, 123(6): 2077-2084. DOI: 10.1007/s13760-022-02169-8.
[18]
ZENG Z, HE J, YAO T. Characteristic early changes of Glu and Cho in brain regions affected by different types of subjective cognitive decline and their clinical significance[J/OL]. Medicine (Baltimore), 2023, 102(49): e36457 [2025-08-11]. https://doi.org/10.1097/MD.0000000000036457. DOI: 10.1097/MD.0000000000036457.
[19]
CAVUS I, PAN J W, HETHERINGTON H P, et al. Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients[J]. Epilepsia, 2008, 49(8): 1358-1366. DOI: 10.1111/j.1528-1167.2008.01603.x.
[20]
MOGHADDAM H S, AARABI M H, MEHVARI-HABIBABADI J, et al. Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy[J]. Neurol Sci, 2021, 42(4): 1411-1421. DOI: 10.1007/s10072-020-04653-6.
[21]
LAM J, DUBOIS J M, ROWLEY J, et al. In vivo hippocampal cornu ammonis 1-3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes[J]. Epilepsia, 2021, 62(7): 1559-1568. DOI: 10.1111/epi.16952.
[22]
BALLERINI A, TALAMI F, MOLINARI M A, et al. Exploring the relationship between amygdala subnuclei volumes and cognitive performance in left-lateralized temporal lobe epilepsy with and without hippocampal sclerosis[J/OL]. Epilepsy Behav, 2023, 145: 109342 [2025-08-11]. https://doi.org/10.1016/j.yebeh.2023.109342. DOI: 10.1016/j.yebeh.2023.109342.47427.
[23]
ALLERINI A, ARIENZO D, STASENKO A, et al. Spatial patterns of gray and white matter compromise relate to age of seizure onset in temporal lobe epilepsy[J/OL]. Neuroimage Clin, 2023, 39: 103473 [2025-08-11]. https://doi.org/10.1016/j.nicl.2023.103473. DOI: 10.1016/j.nicl.2023.103473.
[24]
JUHÁSZ C, HU J, XUAN Y, et al. Imaging increased glutamate in children with Sturge-Weber syndrome: Association with epilepsy severity[J]. Epilepsy Res, 2016, 122: 66-72. DOI: 10.1016/j.eplepsyres.2016.02.010.
[25]
LOPEZ-ACEVEDO M L, MARTINEZ-LOPEZ M, FAVILA R, et al. Secondary MRI-findings, volumetric and spectroscopic measurements in mesial temporal sclerosis: a multivariate discriminant analysis[J/OL]. Swiss Med Wkly, 2012, 142: w13549 [2025-08-11]. https://doi.org/10.4414/smw.2012.13549. DOI: 10.4414/smw.2012.13549.
[26]
CHANG K H, KIM H D, PARK S W, et al. Usefulness of single voxel proton MR spectroscopy in the evaluation of hippocampal sclerosis[J]. Korean J Radiol, 2000, 1(1): 25-32. DOI: 10.3348/kjr.2000.1.1.25.
[27]
BIAGIOLI N, PARFYONOV M, MELETTI S, et al. ILAE neuroimaging task force highlight: The utility of multimodal neuroimaging in diagnostic and presurgical workup of drug-resistant focal epilepsy[J]. Epileptic Disord, 2025, 27(3): 439-450. DOI: 10.1002/epd2.70016.
[28]
RIPART M, DEKRAKER J, ERIKSSON M H, et al. Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID-HS[J]. Ann Neurol, 2024, 97(1): 62-75. DOI: 10.1002/ana.27089.
[29]
BOCHYŃSKA A, WITKOWSKI G, GUGAŁA-IWANIUK M, et al. Volume changes of medial temporal lobe structures in patients with genetic generalized and temporal lobe epilepsy in relation to neuropsychological functions[J]. Postep Psychiatr Neurol, 2022, 31(4): 143-150. DOI: 10.5114/ppn.2022.125029.
[30]
STASENKO A, KAESTNER E, ARIENZO D, et al. Preoperative white matter network organization and memory decline after epilepsy surgery[J]. J Neurosurg, 2023, 139(6): 1576-1587. DOI: 10.3171/2023.4.JNS23347.
[31]
LEE T H, SHIH Y C, LU Y J, et al. Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy[J]. Clin Nucl Med, 2024, 49(4): 294-300. DOI: 10.1097/RLU.0000000000005105.
[32]
JAMALIPOUR SOUFI G, HEKMAT NIA A, HAJALIKHANI P, et al. Correlation of magnetic resonance spectroscopy and magnetic resonance imaging with findings of electroencephalography in patients with temporal lobe epilepsy[J]. J Med Radiat Sci, 2024, 71(1): 51-56. DOI: 10.1002/jmrs.718.
[33]
KHALIFE L, NASREDDINE W, JAAFAR F, et al. Selective correlation of hippocampal volumes with WADA memory scores in mesial temporal sclerosis patients[J/OL]. Front Neurol, 2025, 16: 1507846 [2025-08-11]. https://doi.org/10.3389/fneur.2025.1507846. DOI: 10.3389/fneur.2025.1507846.
[34]
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.
[35]
WU S, WANG Q, ZHAI H, et al. γ-Aminobutyric acid as a biomarker of the lateralizing and monitoring drug effect in patients with magnetic resonance imaging-negative temporal lobe epilepsy[J/OL]. Front Neurosci, 2023, 17: 1184440 [2025-08-11]. https://doi.org/10.3389/fnins.2023.1184440. DOI: 10.3389/fnins.2023.1184440.

PREV Correlation study between brain structural changes and cognitive function in patients with Alzheimer<sup><sup>,</sup></sup>s disease
NEXT Study of changes in brain functional networks in patients with cerebral small vessel disease under different burdens based on rs-fMRI and graph theory analysis
  



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