Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis
Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis
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谷氨酸化学交换饱和转移 (GluCEST) 磁共振成像在脑炎临床前和临床应用中的应用
DOI：
10.3389/fnins.2020.00750
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发表时间：
2020-07-28
影响因子：
4.3
通讯作者：
Wu, Renhua
中科院分区：
文献类型：
--
作者：
Jia, Yanlong;Chen, Yanzi;Wu, Renhua
研究背景脑炎是一种常见的中枢神经系统炎症性疾病，由于缺乏有效的诊断方法，导致误诊率和死亡率高，严重危害人类健康。谷氨酸与小胶质细胞活化密切相关，活化的小胶质细胞是脑炎的关键参与者。因此，使用谷氨酸化学交换饱和转移（GluCEST）成像的脑炎的早期诊断有希望。方法在模型中验证不同浓度谷氨酸和其他主要代谢物的GluCEST成像的灵敏度。将27只患有由金黄色葡萄球菌感染诱导的脑炎的Sprague-Dawley（SD）大鼠用于在7.0特斯拉扫描仪中进行GluCEST成像的临床前研究。在临床研究中，6名脑炎患者、6名腔隙性脑梗死患者和6名健康志愿者在3.0特斯拉扫描仪中接受了GluCEST成像。结果谷氨酸上离水3.0ppm化学位移的胺质子数和GluCEST信号强度均呈浓度依赖性。在生理条件下，谷氨酸是GluCEST信号的主要贡献者。与正常组织相比，在大鼠和脑炎患者中，脑炎区域表现出高强度的GluCEST信号，而腔隙性梗死的GluCEST信号强度降低。在静脉注射免疫球蛋白治疗后，脑炎病变患者显示GluCEST信号降低，结果与治疗前信号显著不同（分别为1.34 ± 0.31 vs 5.0 ± 0.27%; p = 0.000）。结论谷氨酸在脑炎中起重要作用，GluCEST显像信号有可能作为脑炎早期诊断的体内显像生物标志物。GluCEST将为脑炎提供新的见解，并有助于改善脑部疾病的鉴别诊断。
Background Encephalitis is a common central nervous system inflammatory disease that seriously endangers human health owing to the lack of effective diagnostic methods, which leads to a high rate of misdiagnosis and mortality. Glutamate is implicated closely in microglial activation, and activated microglia are key players in encephalitis. Hence, using glutamate chemical exchange saturation transfer (GluCEST) imaging for the early diagnosis of encephalitis holds promise. Methods The sensitivity of GluCEST imaging with different concentrations of glutamate and other major metabolites in the brain was validated in phantoms. Twenty-seven Sprague–Dawley (SD) rats with encephalitis induced by Staphylococcus aureus infection were used for preclinical research of GluCEST imaging in a 7.0-Tesla scanner. For the clinical study, six patients with encephalitis, six patients with lacunar infarction, and six healthy volunteers underwent GluCEST imaging in a 3.0-Tesla scanner. Results The number of amine protons on glutamate that had a chemical shift of 3.0 ppm away from bulk water and the signal intensity of GluCEST were concentration-dependent. Under physiological conditions, glutamate is the main contributor to the GluCEST signal. Compared with normal tissue, in both rats and patients with encephalitis, the encephalitis areas demonstrated a hyper-intense GluCEST signal, while the lacunar infarction had a decreased GluCEST signal intensity. After intravenous immunoglobulin therapy, patients with encephalitis lesions showed a decrease in GluCEST signal, and the results were significantly different from the pre-treatment signal (1.34 ± 0.31 vs 5.0 ± 0.27%, respectively; p = 0.000). Conclusion Glutamate plays a role in encephalitis, and the GluCEST imaging signal has potential as an in vivo imaging biomarker for the early diagnosis of encephalitis. GluCEST will provide new insight into encephalitis and help improve the differential diagnosis of brain disorders.