Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping

Marina Y. Khodanovich, Alena A. Kisel, Andrey E. Akulov, Dmitriy N. Atochin, Marina S. Kudabaeva, Valentina Y. Glazacheva, Michael V. Svetlik, Yana A. Medvednikova, Lilia R. Mustafina, Vasily L. Yarnykh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups (n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.

Original languageEnglish
Pages (from-to)919-931
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume38
Issue number5
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Keywords

  • histology
  • Macromolecular proton fraction
  • magnetic resonance imaging
  • middle cerebral artery occlusion
  • myelin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Khodanovich, M. Y., Kisel, A. A., Akulov, A. E., Atochin, D. N., Kudabaeva, M. S., Glazacheva, V. Y., Svetlik, M. V., Medvednikova, Y. A., Mustafina, L. R., & Yarnykh, V. L. (Accepted/In press). Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping. Journal of Cerebral Blood Flow and Metabolism, 38(5), 919-931. https://doi.org/10.1177/0271678X18755203