Objective: Malformations of cortical development (MCDs) are major causes of intractable epilepsies. To characterize the early neuroimaging findings of MCDs, we tried to identify the MRI features consistent with pathological findings in an infant rat MCD model, prenatally exposed to methylazoxymethanol (MAM), by using newly developed MRI techniques. Methods: At gestational day 15, two doses of MAM (15 mg/kg intraperitoneally) or normal saline were injected into pregnant rats. The offspring underwent in vivo MRI, including glutamate chemical exchange saturation transfer (GluCEST), 1H-MR spectroscopy, and diffusion tensor imaging, at postnatal day (P) 15 using a 7T small-animal imaging system. Another set of prenatally MAM-exposed rats were sacrificed for histological staining. Results: At P15, the retrosplenial cortex (RSC) of rats with MCDs showed decreased neuronal nuclei, parvalbumin, and reelin expressions. Moreover, dendritic arborization of pyramidal cells in the RSC significantly decreased in infant rats with MCDs. In vivo MRI showed significantly decreased GluCEST (%) in the RSC of rats with MCDs (p = 0.000) and a significant correlation between GluCEST (%) and RSC thickness (r = 0.685, p = 0.003). The rats with MCDs showed reduced glutamate (p = 0.002), N-acetylaspartate (p = 0.002), and macromolecule and lipid levels (p = 0.027) and significantly reduced fractional anisotropy values in the RSC. Conclusion: In vivo MRI revealed reduced neuronal population and dendritic arborization in the RSC of infant rats with MCDs during the early postnatal period. These pathological changes of the cortex could serve as clinical imaging biomarkers of MCDs in infants.

中文翻译：

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体内 MRI 成功揭示幼鼠皮层发育畸形

目的：皮质发育畸形（MCDs）是顽固性癫痫的主要原因。为了表征 MCD 的早期神经影像学发现，我们试图通过使用新开发的 MRI 技术，在产前暴露于甲基偶氮甲醇 (MAM) 的婴儿大鼠 MCD 模型中确定与病理结果一致的 MRI 特征。方法：在妊娠第 15 天，将 2 剂 MAM（15 mg/kg 腹腔注射）或生理盐水注射到妊娠大鼠体内。后代在出生后第 15 天 (P) 使用 7T 小动物成像系统进行了体内 MRI，包括谷氨酸化学交换饱和转移 (GluCEST)、1H-MR 光谱和扩散张量成像。另一组出生前暴露于 MAM 的大鼠被处死用于组织学染色。结果：在 P15，MCD 大鼠的脾后皮层 (RSC) 显示神经元核、小清蛋白和 reelin 表达减少。此外，在患有 MCD 的婴儿大鼠中，RSC 中锥体细胞的树突状细胞明显减少。体内 MRI 显示 MCD 大鼠 RSC 的 GluCEST (%) 显着降低 (p = 0.000)，并且 GluCEST (%) 与 RSC 厚度之间存在显着相关性 (r = 0.685, p = 0.003)。患有 MCD 的大鼠的谷氨酸 (p = 0.002)、N-乙酰天冬氨酸 (p = 0.002) 以及大分子和脂质水平 (p = 0.027) 降低，并且 RSC 中的分数各向异性值显着降低。结论：体内 MRI 显示在出生后早期患有 MCD 的幼鼠 RSC 中神经元群和树突分支减少。