Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model

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 parti...

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Veröffentlicht in:Scientific reports 2017-04, Vol.7 (1), p.46686, Article 46686
Hauptverfasser: Khodanovich, Marina Yu, Sorokina, Irina V., Glazacheva, Valentina Yu, Akulov, Andrey E., Nemirovich-Danchenko, Nikolay M., Romashchenko, Alexander V., Tolstikova, Tatyana G., Mustafina, Lilia R., Yarnykh, Vasily L.
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creator Khodanovich, Marina Yu
Sorokina, Irina V.
Glazacheva, Valentina Yu
Akulov, Andrey E.
Nemirovich-Danchenko, Nikolay M.
Romashchenko, Alexander V.
Tolstikova, Tatyana G.
Mustafina, Lilia R.
Yarnykh, Vasily L.
description 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 
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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 &lt; 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 &lt; 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). 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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 &lt; 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 &lt; 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28436460</pmid><doi>10.1038/srep46686</doi><oa>free_for_read</oa></addata></record>
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subjects 13/51
631/1647/245/1628
631/378/2606/1666
Animals
Anterior commissure
Biomarkers
Brain
Brain mapping
Corpus callosum
Cuprizone
Demyelination
Histology
Humanities and Social Sciences
Macromolecules
Magnetic resonance imaging
multidisciplinary
Multiple sclerosis
Myelin
Neuroimaging
NMR
Nuclear magnetic resonance
Regions
Regression analysis
Science
Substantia alba
Substantia grisea
Thalamus
Variance analysis
title Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model
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