Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model.
Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model.
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DOI：
10.1038/srep46686
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发表时间：
2017-04-24
影响因子：
4.6
通讯作者：
Yarnykh VL
中科院分区：
文献类型：
--
作者：
Khodanovich MY;Sorokina IV;Glazacheva VY;Akulov AE;Nemirovich-Danchenko NM;Romashchenko AV;Tolstikova TG;Mustafina LR;Yarnykh VL
在多发性硬化症的临床前研究中，铜唑酮诱导的小鼠脱髓鞘是一种常用的模型。最近的定量临床靶向MRI方法，快速大分子质子分数（MPF）映射显示了作为人类和动物研究中髓鞘生物标志物的前景，具有对白色物质（WM）和灰质（GM）脱髓鞘敏感的特别优势。本研究旨在组织学验证MPF映射的能力，以量化髓鞘损失的脑组织中使用铜氮脱髓鞘模型。采用快速单点合成参考法，在11.7T动物MRI扫描仪上获得了7只铜唑酮处理的和7只对照的BALB/c 57 BL/6小鼠的全脑MPF图。用Luxol Fast Blue（LFB）对脑切片进行组织学染色以用于髓鞘定量。根据LFB染色和MPF，在所有解剖结构（胼胝体、前连合、内囊、丘脑、尾壳核和皮质）中发现了显著（p < 0.05）的去髓鞘。MPF与所有动物（r = 0.95，p < 0.001）以及单独的治疗组和对照组（分别为r = 0.96，p = 0.002和r = 0.93，p = 0.007）的定量组织学密切相关。组织学髓鞘染色和MPF之间的密切协议表明，快速MPF映射，使强大的和准确的定量评估在WM和GM的脱髓鞘。
Cuprizone-induced demyelination in mice is a frequently used model in preclinical multiple sclerosis research. A recent quantitative clinically-targeted MRI method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise as a myelin biomarker in human and animal studies with a particular advantage of sensitivity to both white matter (WM) and gray matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping to quantify myelin loss in brain tissues using the cuprizone demyelination model. Whole-brain MPF maps were obtained in vivo on an 11.7T animal MRI scanner from 7 cuprizone-treated and 7 control С57BL/6 mice using the fast single-point synthetic-reference method. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. Significant (p < 0.05) demyelination in cuprizone-treated animals was found according to both LFB staining and MPF in all anatomical structures (corpus callosum, anterior commissure, internal capsule, thalamus, caudoputamen, and cortex). MPF strongly correlated with quantitative histology in all animals (r = 0.95, p < 0.001) as well as in treatment and control groups taken separately (r = 0.96, p = 0.002 and r = 0.93, p = 0.007, respectively). Close agreement between histological myelin staining and MPF suggests that fast MPF mapping enables robust and accurate quantitative assessment of demyelination in both WM and GM.