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利用多模态 MRI 研究杯状病毒模型中的脱髓鞘和髓鞘再生。

Probing demyelination and remyelination of the cuprizone mouse model using multimodality MRI.

机构信息

Center for in vivo Microscopy, Duke University, Durham, North Carolina, USA.

Brain Imaging and Analysis Center, Duke University, Durham, North Carolina, USA.

出版信息

J Magn Reson Imaging. 2019 Dec;50(6):1852-1865. doi: 10.1002/jmri.26758. Epub 2019 Apr 22.

Abstract

BACKGROUND

Various studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking.

PURPOSE

To investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination.

STUDY TYPE

Prospective.

ANIMAL MODEL

A cuprizone mice model with an age-matched control group (n = 5), 4-week cuprizone exposure group followed by 9-week on a normal diet (n = 6), and a 13-week cuprizone exposure group (n = 6).

FIELD STRENGTH/SEQUENCE: 3D gradient recalled echo, T -weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T.

ASSESSMENT

Quantification of DTI metrics, quantitative susceptibility mapping (QSM), and T -weighted imaging intensity in major white matter bundles.

STATISTICAL TESTS

Nonparametric permutation tests were used with a cluster-forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family-wise correction.

RESULTS

In vivo susceptibility values increased from -11.7 to -0.7 ppb (P < 0.001) in CC and from -13.7 to -5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13-week cuprizone exposure. Ex vivo susceptibility values increased from -25.4 to 7.4 ppb (P < 0.001) in CC and from -41.6 to -15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel-based analysis.

DATA CONCLUSION

QSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T -weighted images and DTI metrics.

LEVEL OF EVIDENCE

2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1852-1865.

摘要

背景

多项 MRI 研究表明,胼胝体(CC)是最容易受到铜锌失衡饮食干预的部位,然而,使用不同的 MRI 参数来检测脱髓鞘和髓鞘再生过程的方法仍存在不足。

目的

探讨多参数 MRI 活体和离体检测脱髓鞘和髓鞘再生的敏感性。

研究类型

前瞻性。

动物模型

年龄匹配的对照组(n = 5)、4 周铜锌失衡饮食暴露组(n = 6),随后进行 9 周正常饮食喂养,以及 13 周铜锌失衡饮食暴露组(n = 6)的杯状醇诱导的少突胶质细胞损伤的雄性 C57BL/6 小鼠模型。

磁场强度/序列:7.0T 和 9.4T 的 3D 梯度回波、T2 加权和弥散张量成像(DTI)。

评估

主要白质束的 DTI 指标、定量磁化率图(QSM)和 T2 加权成像强度的定量分析。

统计学检验

采用非参数置换检验,簇形成阈值为 3.09(相当于 P = 0.001),并进行了基于家族的校正,显著水平为 P = 0.05。

结果

在 13 周铜锌失衡饮食暴露后,活体 CC 的磁化率值从-11.7 增加到-0.7 ppb(P < 0.001),AC 的磁化率值从-13.7 增加到-5.1 ppb(P < 0.001)。离体 CC 的磁化率值从-25.4 增加到 7.4 ppb(P < 0.001),AC 的磁化率值从-41.6 增加到-15.8 ppb(P < 0.001)。活体研究中,磁化率值对脱髓鞘具有高变异性(CC 为 94.0%,AC 为 62.8%)。与离体研究中的径向扩散系数相比,磁化率值具有更高的变异性(CC 为 129.1%,AC 为 62.0%)。除了不同白质束的差异磁化率变化外,基于体素的分析还显示,不仅在 CC 区域,而且在 AC 区域也存在脱髓鞘的区域内变化。

结论

QSM 对杯状醇暴露引起的脱髓鞘过程敏感,可作为传统 T2 加权图像和 DTI 指标的补充技术。

证据水平

2 技术功效分期:2 J. Magn. Reson. Imaging 2019;50:1852-1865.

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