Diffusion Kurtosis Imaging maps neural damage in the EAE model of multiple sclerosis.

Diffusion Kurtosis Imaging maps neural damage in the EAE model of multiple sclerosis.
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DOI:
10.1016/j.neuroimage.2019.116406
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发表时间:
2020-03
期刊:
影响因子:
5.7
通讯作者:
Jespersen, Sune Norhoj
Jespersen, Sune Norhoj
中科院分区:
医学1区
文献类型:
--
作者:
Chuhutin, Andrey;Hansen, Brian;Wlodarczyk, Agnieszka;Owens, Trevor;Shemesh, Noam;Jespersen, Sune Norhoj

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扩散峰度成像(DKI)是一种成像方式,产生新的疾病生物标志物,并与神经组织建模相结合,提供了访问微观结构参数。最近,DKI和随后的微结构模型参数的估计已被用于评估神经退行性疾病和相关动物模型中的组织变化。在这项研究中,从多发性硬化症(MS)的实验性自身免疫性脑脊髓炎(EAE)模型的小鼠脊髓进行了研究,第一次使用DKI结合生物物理建模,以研究微观结构指标和动物功能障碍程度之间的关系。从具有不同等级残疾的动物中提取13条脊髓,并在高场MRI扫描仪中与5个对照标本一起进行沿着扫描。扩散加权数据与高分辨率T2* 图像一起采集。拟合扩散数据以估计扩散和峰度张量以及白色物质建模参数,这些参数均用于使用线性混合效应模型的后续统计分析。T2* 图像用于描绘局灶性脱髓鞘/炎症。我们的研究结果揭示了残疾和正常出现的白色物质和灰质的微结构参数之间的密切关系。残疾与峰度张量、径向峰度、径向扩散率的平均值之间的关系与其他低髓鞘化MS模型和患者中发现的相似。然而,生物物理建模参数的变化,特别是在轴索外轴向扩散率明显不同于以往的研究采用其他动物模型的MS。总之,我们的数据表明,DKI和微观结构建模可以提供一个独特的对比能够检测EAE的具体变化与临床残疾。
Diffusion kurtosis imaging (DKI) is an imaging modality that yields novel disease biomarkers and in combination with nervous tissue modeling, provides access to microstructural parameters. Recently, DKI and subsequent estimation of microstructural model parameters has been used for assessment of tissue changes in neurodegenerative diseases and associated animal models. In this study, mouse spinal cords from the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) were investigated for the first time using DKI in combination with biophysical modeling to study the relationship between microstructural metrics and degree of animal dysfunction. Thirteen spinal cords were extracted from animals with varied grades of disability and scanned in a high-field MRI scanner along with five control specimen. Diffusion weighted data were acquired together with high resolution T2* images. Diffusion data were fit to estimate diffusion and kurtosis tensors and white matter modeling parameters, which were all used for subsequent statistical analysis using a linear mixed effects model. T2* images were used to delineate focal demyelination/inflammation. Our results reveal a strong relationship between disability and measured microstructural parameters in normal appearing white matter and gray matter. Relationships between disability and mean of the kurtosis tensor, radial kurtosis, radial diffusivity were similar to what has been found in other hypomyelinating MS models, and in patients. However, the changes in biophysical modeling parameters and in particular in extra-axonal axial diffusivity were clearly different from previous studies employing other animal models of MS. In conclusion, our data suggest that DKI and microstructural modeling can provide a unique contrast capable of detecting EAE-specific changes correlating with clinical disability.
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