In vivo diffusion tensor imaging (DTI) of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis (ALS). Ten mice with TDP-43G298S overexpression under control of the Thy1.2 promoter and 10 wild type (wt) underwent longitudinal DTI scans at 11.7 T, including one baseline and one follow-up scan with an interval of about 5 months. Whole brain-based spatial statistics (WBSS) of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43G298S mice compared to wt at the cohort level. Results were supplemented by tractwise fractional anisotropy statistics (TFAS) and histological evaluation of motor cortex for signs of neuronal loss. Alterations at the cohort level in TDP-43G298S mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal tract. Neuronal loss in layer V of motor cortex was detected in TDP-43G298S at the later (but not at the earlier) timepoint compared to wt. DTI mapping of TDP-43G298S mice demonstrated progression in motor areas M1/M2. WBSS and TFAS are useful techniques to localize TDP-43G298S associated alterations over time in this ALS mouse model, as a biological marker.

中文翻译：

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队列水平的纵向扩散张量磁共振成像分析显示 TDP-43G298S ALS 小鼠模型中皮质和胼胝体微结构受到干扰，皮质脊髓束未受影响

小鼠大脑的体内扩散张量成像 (DTI) 用于识别肌萎缩侧索硬化 (ALS) 小鼠模型中与 TDP-43 相关的改变。在 Thy1.2 启动子控制下 TDP-43G298S 过表达的 10 只小鼠和 10 只野生型 (wt) 在 11.7 T 下进行纵向 DTI 扫描，包括一次基线和一次间隔约 5 个月的随访扫描。基于 DTI 的参数图的基于全脑的空间统计 (WBSS) 用于识别 TDP-43G298S 小鼠与队列水平的 wt 相比的纵向变化。结果补充了束状各向异性分数统计 (TFAS) 和运动皮层的组织学评估，以寻找神经元丢失的迹象。在 TDP-43G298S 小鼠中，在运动区 M1/M2 和经胼胝体纤维中横断面和纵向观察到队列水平的变化，但在皮质脊髓束中没有。与 wt 相比，TDP-43G298S 在较晚（但不在较早）时间点检测到运动皮层 V 层的神经元损失。TDP-43G298S 小鼠的 DTI 映射显示运动区域 M1/M2 的进展。WBSS 和 TFAS 是在此 ALS 小鼠模型中定位 TDP-43G298S 相关变化随时间变化的有用技术，作为生物标记。