Mueller Christina, Hong Huixian, Sharma Ayushe A, Qin Hongwei, Benveniste Etty N, Szaflarski Jerzy P
Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Cell, Developmental and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Epilepsia Open. 2024 Dec;9(6):2454-2466. doi: 10.1002/epi4.13082. Epub 2024 Oct 29.
Epileptogenesis is linked to neuroinflammation. We hypothesized that local heat production caused by neuroinflammation can be visualized non-invasively in vivo via brain magnetic resonance spectroscopic imaging (MRSI) and MRSI-thermometry (MRSI-t) and that there is a relationship in patients with temporal lobe epilepsy (TLE) between MRSI-t and brain metabolites choline and myo-inositol and between neuroimaging and cellular and serum biomarkers of inflammation.
Thirty-six (36) participants, 18 with temporal lobe epilepsy (13 females) and 18 age-matched healthy controls (nine females), were enrolled prospectively and underwent MRSI/MRSI-t; TLE participants also provided blood samples. Temperature was measured using creatine as a reference metabolite. Analysis of Functional NeuroImages 3dttest++ tool was used to analyze voxel-level group differences in temperature, choline, and myo-inositol. Associations with immune cell subsets, cytokines, and chemokines related to inflammation were quantified using correlation coefficients with significant relationships as noted.
Patients with TLE showed elevated temperature, choline, and myo-inositol in the temporal lobes. Higher brain temperature was associated with higher levels of cytokines and chemokines, including GM-CSF, TNF, IL-1β, and IL - 12p70, and lower frequency of immune cells including CD3 T-cells, CD4 T-cells, CD8 T-cells, and classical monocytes. Higher choline was associated with higher levels of the cytokines including LT-α, IL-13, and IL-4, and higher myo-inositol was associated with a higher frequency of CD4 T-cell and CD19 B-cell subsets and higher levels of cytokines and chemokines including LT-α, IL-13, and CCL3.
This study, for the first time, showed that in temporal lobes of patients with TLE temperature and metabolite changes correlate with cellular and serum biomarkers of inflammation. Our results provide support for further development of MRSI-t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool.
Neuroinflammation is associated with excessive heat production which can be visualized with magnetic resonance spectroscopic imaging and thermometry (MRSI-t). We prospectively investigated the relationship between MRSI-t and cellular and serum measures of peripheral inflammation in patients with temporal lobe epilepsy (TLE); we compared the results of MRSI-t in patients with TLE to healthy controls. We showed a relationship between the temperature elevations in TLE and elevations of various measures of peripheral inflammation. Our results support further development of MRSI-t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool.
癫痫发生与神经炎症有关。我们假设神经炎症引起的局部产热可通过脑磁共振波谱成像（MRSI）和MRSI测温法（MRSI-t）在体内进行无创可视化，并且在颞叶癫痫（TLE）患者中，MRSI-t与脑代谢物胆碱和肌醇之间存在关联，同时神经影像学与炎症的细胞和血清生物标志物之间也存在关联。
前瞻性招募了36名参与者，其中18名颞叶癫痫患者（13名女性）和18名年龄匹配的健康对照者（9名女性），并对他们进行了MRSI/MRSI-t检查；TLE患者还提供了血样。使用肌酸作为参考代谢物测量温度。使用功能性神经影像分析3dttest++工具分析温度、胆碱和肌醇的体素水平组间差异。使用相关系数对与炎症相关的免疫细胞亚群、细胞因子和趋化因子的关联进行量化，并记录显著关系。
TLE患者颞叶的温度、胆碱和肌醇升高。较高的脑温与较高水平的细胞因子和趋化因子相关，包括粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子（TNF）、白细胞介素-1β（IL-1β）和白细胞介素-12p70，以及较低频率的免疫细胞，包括CD3 T细胞、CD4 T细胞、CD8 T细胞和经典单核细胞。较高的胆碱与较高水平的细胞因子相关，包括淋巴毒素-α（LT-α）、白细胞介素-13（IL-13）和白细胞介素-4（IL-4），较高的肌醇与较高频率的CD4 T细胞和CD19 B细胞亚群以及较高水平的细胞因子和趋化因子相关，包括LT-α、IL-13和CCL3。
本研究首次表明，在TLE患者的颞叶中，温度和代谢物变化与炎症的细胞和血清生物标志物相关。我们的结果为进一步开发MRSI-t作为癫痫及潜在其他神经系统疾病中神经炎症的一种测量方法以及作为一种研究和临床工具提供了支持。
神经炎症与过多的产热有关，产热可通过磁共振波谱成像和测温法（MRSI-t）进行可视化。我们前瞻性地研究了MRSI-t与颞叶癫痫（TLE）患者外周炎症的细胞和血清指标之间的关系；我们将TLE患者的MRSI-t结果与健康对照者进行了比较。我们发现TLE患者的体温升高与外周炎症的各种指标升高之间存在关联。我们的结果支持进一步开发MRSI-t作为癫痫及潜在其他神经系统疾病中神经炎症的一种测量方法以及作为一种研究和临床工具。
