西藏小型猪缺氧缺血性脑病模型的建立及病理和影像学表现

Pathological and magnetic resonance imaging findings in a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy

目的：建立西藏小型猪缺氧缺血性脑病（HIE）模型，观察HIE模型MR表现并与病理结果对照。方法1~3 d龄西藏小型猪6只（模型组4只，对照组2只）。模型组夹闭双侧颈总动脉放入缺氧箱内（氧浓度为8%），60 min后，复氧及再灌注。对照组仅进行双侧颈总动脉分离。模型组于模型建立后2 h、24 h、3 d、5 d进行脑部ESWAN检查。对照组于手术后2 h进行脑部增强T2＊加权的血管成像（enhanced T2 star weighted angiography, ESWAN）检查。常规MR检查采用SE序列T2FLAIR、T2WI及DWI，于模型建立后24 h进行。最后进行病理学检查。结果新纹状体区T2＊值于模型建立后3 d达峰值，不同时间点与对照组T2＊值差异有统计学意义（P〈0.05）。皮层下白质区T2＊值于模型建立后24 h达峰值（P〈0.05）。新纹状体区R2＊值于模型建立后3 d达最低值，不同时间点与对照组差异有统计学意义（P〈0.05），皮层下白质区R2＊值于模型建立后24 h达最低值（P〈0.05）。Magnitude值于模型建立后明显升高（P〈0.05）。模型组动物脑部MR的DWI成像可见双侧额部皮层下白质及双侧新纹状体略高信号， T2FLAIR信号变化不显著，T2WI未见明显异常。SWI可见粗大髓静脉及微出血。HIE早期病理变化以水肿及静脉淤血为主，偶见局灶性坏死及含铁血黄素沉积。结论 ESWAN序列可以评价HIE是否有出血及脑组织水肿。T2＊值、R2＊值、幅度值可用于观察缺氧缺血性脑损伤的发生发展变化。

Objective To establish a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy and evaluate the magnetic resonance imaging （MRI） manifestations and pathological findings. Methods Six neonatal （1-3 days old） Tibet minipigs were randomized into model group （n=4） and control group （n=2）. In model group, hypoxic- ischemic encephalopathy was induced by surgical ligation of the bilateral carotid artery followedimmediately by hypoxic exposure in a hypoxia chamber for 1 h. ESWAN was performed at 2 h, 24 h, 3 days and 5 days after induction of HIE or at 2 h after sham surgery in the control animals to evaluate the brain damage. Conventional MRI scans （T2FLAIR, T2WI, and DWI） were also performed at 24 h after the modeling. Results In the neostriatum, values of T2＊-weighted MRI increased and reached the peak level at 3 days post-injury （P〈0.05）. Subcortical white matter T2＊values reached the peak level at 24 h （P〈0.05）. Neostriatum R2＊values were at the lowest level at 3 days （P〈0.05）. Magnitude values were significantly increased after the model establishment （P〈0.05）. DWI showed multiple mild focal high signals in the bifrontal subcortical white matter and bilateral neostriatum;T2FLAIR showed slightly increased signal; T2WI showed no obvious abnormalities. SWI showed dilated medulla veins adjacent to the bilateral lateral ventricles and basal ganglia. In the early stage of HIE, brain pathologies were characterized mainly by edema and venous congestion with occasional focal necrosis and hemosiderin deposition. Conclusion ESWAN sequence is capable of detecting bleeding and brain edema, and T2＊, R2＊, and magnitude values can be used to estimate the changes of brain damage following HIE.