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 Full article

Journal

Scientific Reports
ISSN: 2045-2322

Output data

Year: 2017, Volume: 7, Article number : 46686, Pages count : DOI: 10.1038/srep46686

Authors

Khodanovich Marina Yu ¹ , Sorokina Irina V. ² , Glazacheva Valentina Yu ¹ , Akulov Andrey E. ^1,3 , Nemirovich-Danchenko Nikolay M. ¹ , Romashchenko Alexander V. ³ , Tolstikova Tatyana G. ² , Mustafina Lilia R. ⁴ , Yarnykh Vasily L. ^1,5

Affiliations

1	(Данные Web of science) Tomsk State Univ, Res Inst Biol & Biophys, Tomsk, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Organ Chem, Novosibirsk, Russia
3	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk, Russia
4	(Данные Web of science) Siberian State Med Univ, Tomsk, Russia
5	(Данные Web of science) Univ Washington, Dept Radiol, Seattle, WA 98195 USA

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.57BL/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.

Khodanovich M.Y. , Sorokina I.V. , Glazacheva V.Y. , Akulov A.E. , Nemirovich-Danchenko N.M. , Romashchenko A.V. , Tolstikova T.G. , Mustafina L.R. , Yarnykh V.L.
Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model

Scientific Reports. 2017. V.7. 46686 . DOI: 10.1038/srep46686 WOS Scopus

Full text from publisher

Published online:	Apr 24, 2017
Published print:	May 1, 2017

Web of science	WOS:000400057800001
Scopus	2-s2.0-85029596727
OpenAlex	W2608116788