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通过体内磁共振显微成像监测转基因小鼠中阿尔茨海默氏β-淀粉样蛋白斑块发展的纵向评估。

Longitudinal assessment of Alzheimer's beta-amyloid plaque development in transgenic mice monitored by in vivo magnetic resonance microimaging.

作者信息

Braakman Niels, Matysik Jörg, van Duinen Sjoerd G, Verbeek Fons, Schliebs Reinhard, de Groot Huub J M, Alia A

机构信息

Solid State NMR Group, Leiden Institute of Chemistry, Gorlaeus Laboratoria, Leiden, The Netherlands.

出版信息

J Magn Reson Imaging. 2006 Sep;24(3):530-6. doi: 10.1002/jmri.20675.

Abstract

PURPOSE

To assess the development of beta-amyloid (Abeta) plaques in the brain with age in the transgenic mouse model of Alzheimer's disease (AD) pathology by in vivo magnetic resonance microimaging (microMRI).

MATERIALS AND METHODS

Live transgenic mice (Tg2576) and nontransgenic littermates (control) were studied at regular intervals between the ages of 12 and 18 months. Plaques were visualized using a T(2)-weighted rapid acquisition with relaxation enhancement (RARE) sequence. Changes in T(2) relaxation times were followed using a multislice multiecho (MSME) sequence. Plaque load and numerical density in MR images were calculated using SCIL image software.

RESULTS

Abeta plaques were clearly detected with the T(2)-weighted RARE sequence in the hippocampal and cortical regions of the brain of Tg2576 mice but not in control mice. Following the plaque development in the same animals with age showed that plaque area, number, and size increased markedly, while T(2) relaxation time showed a decreasing trend with age.

CONCLUSION

These results demonstrate that microMRI is a viable method for following the development of Abeta plaques in vivo, and suggest that this method may be feasible for assessing the effect of therapeutic interventions over time in the same animals.

摘要

目的

通过体内磁共振显微成像(显微MRI)评估阿尔茨海默病(AD)病理转基因小鼠模型中大脑β-淀粉样蛋白(Aβ)斑块随年龄的发展情况。

材料与方法

在12至18个月龄期间定期研究活体转基因小鼠(Tg2576)和非转基因同窝小鼠(对照)。使用具有弛豫增强的T(2)加权快速采集(RARE)序列使斑块可视化。使用多层多回波(MSME)序列跟踪T(2)弛豫时间的变化。使用SCIL图像软件计算MR图像中的斑块负荷和数值密度。

结果

在Tg2576小鼠大脑的海马和皮质区域,使用T(2)加权RARE序列可清晰检测到Aβ斑块,而对照小鼠中未检测到。随着同一动物中斑块随年龄发展,结果显示斑块面积、数量和大小显著增加,而T(2)弛豫时间随年龄呈下降趋势。

结论

这些结果表明显微MRI是一种在体内跟踪Aβ斑块发展的可行方法,并表明该方法对于评估同一动物中治疗干预随时间的效果可能是可行的。

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