Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis
Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis
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DOI：
10.1016/j.neuroimage.2019.116138
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发表时间：
2019-11-15
期刊：
影响因子：
5.7
通讯作者：
Febo, Marcelo
中科院分区：
文献类型：
--
作者：
Colon-Perez, Luis M.;Ibanez, Kristen R.;Febo, Marcelo
细胞外β-淀粉样蛋白（A β）斑块沉积和炎症免疫激活被认为会改变组织微观结构的各个方面，如细胞外游离水、分数各向异性和扩散率，以及轴突突起的密度和几何排列。量化阿尔茨海默病和相关神经退行性痴呆的这些微结构变化可以用于监测或预测疾病进程。在本研究中，我们使用高场扩散磁共振成像（dMRI），以调查A β和炎性白细胞介素-6（IL-6），单独或组合，在TgCRND 8阿尔茨海默氏症-A β沉积小鼠模型体内组织微结构的影响。在8月龄时，使用2壳、54梯度方向的dMRI序列在11.1 T下扫描表达脑靶向IL 6或增强型胶质细胞增生蛋白的TgCRND 8和非转基因（nTg）小鼠（EGFP对照）。图像处理采用扩散张量成像（DTI）模型或神经突方向弥散和密度成像（NODDI）模型。TgCRND 8小鼠的DTI和NODDI处理显示白色物质（WM）和海马的微观结构模式与径向和纵向扩散缺陷沿着轴突和树突状突起的密度和几何复杂性增加一致。这包括减少FA，平均，轴向和径向扩散，并增加方向分散（ODI）和细胞内体积分数（ICVF）在WM和海马中测量。在TgCRND 8小鼠中，IL 6对WM FA产生“保护样”作用，观察到FA增加，抵消了内源性A β产生和积累所观察到的FA减少。此外，我们发现ICVF和ODI与功能连接体聚集系数呈反比关系。NODDI和图论指标之间的关系表明，目前未知的WM和海马体的微结构改变与大脑中功能网络组织的减少有关。
Extracellular beta-amyloid (A beta) plaque deposits and inflammatory immune activation are thought to alter various aspects of tissue microstructure, such as extracellular free water, fractional anisotropy and diffusivity, as well as the density and geometric arrangement of axonal processes. Quantifying these microstructural changes in Alzheimer's disease and related neurodegenerative dementias could serve to monitor or predict disease course. In the present study we used high-field diffusion magnetic resonance imaging (dMRI) to investigate the effects of A beta and inflammatory interleukin-6 (IL6), alone or in combination, on in vivo tissue microstructure in the TgCRND8 mouse model of Alzheimer's-type A beta deposition. TgCRND8 and non-transgenic (nTg) mice expressing brain-targeted IL6 or enhanced glial fibrillary protein (EGFP controls) were scanned at 8 months of age using a 2-shell, 54-gradient direction dMRI sequence at 11.1 T. Images were processed using the diffusion tensor imaging (DTI) model or the neurite orientation dispersion and density imaging (NODDI) model. DTI and NODDI processing in TgCRND8 mice revealed a microstructure pattern in white matter (WM) and hippocampus consistent with radial and longitudinal diffusivity deficits along with an increase in density and geometric complexity of axonal and dendritic processes. This included reduced FA, mean, axial and radial diffusivity, and increased orientation dispersion (ODI) and intracellular volume fraction (ICVF) measured in WM and hippocampus. IL6 produced a 'protective-like' effect on WM FA in TgCRND8 mice, observed as an increased FA that counteracted a reduction in FA observed with endogenous A beta production and accumulation. In addition, we found that ICVF and ODI had an inverse relationship with the functional connectome clustering coefficient. The relationship between NODDI and graph theory metrics suggests that currently unknown microstructure alterations in WM and hippocampus are associated with diminished functional network organization in the brain.