Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging.

Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging.
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DOI:
10.21769/bioprotoc.4221
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发表时间:
2021-11-20
期刊:
影响因子:
0.8
通讯作者:
Kaffman A
Kaffman A
中科院分区:
其他
文献类型:
--
作者:
Arefin TM;Lee CH;White JD;Zhang J;Kaffman A

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啮齿动物的转化工作阐明了驱动与精神和神经疾病相关的复杂行为的基本机制。然而,许多有希望的啮齿动物研究后来在临床试验中失败,突出了提高啮齿动物临床前研究的转化效用的必要性。小型啮齿动物的成像为解决这一挑战提供了一个重要的策略,因为它可以对结构和动态变化进行全脑无偏搜索,可以直接与人类成像进行比较。利用成像技术鉴定的结构变化的功能意义,然后可以利用小鼠可用的分子和遗传工具进一步研究。在这里,我们描述了一个无偏搜索和表征结构变化和网络特性的管道,基于覆盖整个小鼠大脑的扩散MRI数据,各向同性分辨率为100µm。我们首先使用无偏倚的基于全脑体素的分析来确定暴露于不可预测的产后应激(UPS)的成年小鼠大脑的体积和微观结构变化,UPS是一种复杂早期生活应激(ELS)的小鼠模型。显示结构异常的大脑区域作为节点生成网格,用于基于图论评估结构连通性和网络特性。这里描述的技术可以广泛应用于理解其他人类疾病小鼠模型中的大脑连接,以及转基因小鼠品系。图形摘要:利用扩散磁共振成像技术表征小鼠脑结构连接体的管道。比例尺= 1mm。
Translational work in rodents elucidates basic mechanisms that drive complex behaviors relevant to psychiatric and neurological conditions. Nonetheless, numerous promising studies in rodents later fail in clinical trials, highlighting the need for improving the translational utility of preclinical studies in rodents. Imaging of small rodents provides an important strategy to address this challenge, as it enables a whole-brain unbiased search for structural and dynamic changes that can be directly compared to human imaging. The functional significance of structural changes identified using imaging can then be further investigated using molecular and genetic tools available for the mouse. Here, we describe a pipeline for unbiased search and characterization of structural changes and network properties, based on diffusion MRI data covering the entire mouse brain at an isotropic resolution of 100 µm. We first used unbiased whole-brain voxel-based analyses to identify volumetric and microstructural alterations in the brain of adult mice exposed to unpredictable postnatal stress (UPS), which is a mouse model of complex early life stress (ELS). Brain regions showing structural abnormalities were used as nodes to generate a grid for assessing structural connectivity and network properties based on graph theory. The technique described here can be broadly applied to understand brain connectivity in other mouse models of human disorders, as well as in genetically modified mouse strains. Graphic abstract: Pipeline for characterizing structural connectome in the mouse brain using diffusion magnetic resonance imaging. Scale bar = 1 mm.