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An in vivo implementation of the MEX MRI for myelin fraction of mice brain

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Abstract

Objective

Magnetization EXchange (MEX) sequence measures a signal linearly dependent on the myelin proton fraction by selective suppression of water magnetization and a recovery period. Varying the recovery period enables extraction of the percentile fraction of myelin bound protons. We aim to demonstrate the MEX sequence sensitivity to the fraction of protons associated with myelin in mice brain, in vivo.

Methods

The cuprizone mouse model was used to manipulate the myelin content. Mice fed cuprizone (n = 15) and normal chow (n = 8) were imaged in vivo using MEX sequence. MR images were segmented into corpus callosum and internal capsule (white matter) and cortical gray matter, and fitted to the recovery equation. Results were analyzed with correlation to MWF and histopathology.

Results

The extracted parameters show significant differences in the corpus callosum between the cuprizone and control groups. The cuprizone group exhibited reduced myelin fraction 26.5% (P < 0.01). The gray matter values were less affected, with 13.5% reduction (P < 0.05); no changes were detected in the internal capsule. Results were validated by MWF scans and good correlation to the histology analysis (R2 = 0.685).

Conclusion

The results of this first in vivo implementation of the MEX sequence provide a quantitative measure of demyelination in brain white matter.

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Abbreviations

MT:

Magnetization transfer

UTE:

Ultra-short TE

MWF:

Myelin water fraction

MEX:

Magnetization exchange

GM:

Gray matter

WM:

White matter

SIR:

Selective inversion recovery

MS:

Multiple sclerosis

EAE:

Experimental autoimmune encephalitis

ROI:

Region of interest

CC:

Corpus callosum

sCC:

Splenium corpus callosum

cGM:

Cortical gray matter

IC:

Internal capsule

FLASH:

Fast low angle shot

MSME:

Multi-slice-multi-echo

RARE:

Rapid acquisition with relaxation enhancement

MBP:

Myelin basic protein

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Acknowledgements

This work is dedicated to the memory of our beloved colleague and NMR mentor, Dr. Uzi Eliav. Dr. Eliav’s role over the years in developing multiple NMR methods, including the MEX method, and his role in this particular work were pivotal. His friendship and wisdom will be missed.

Funding

This study was facilitated by funding from the Israeli Science Foundation (ISF grant no. 1585/17) granted to U.N. and from the U.S.‐Israel Binational Science Foundation (BSF grant no. 2013253) to G.N. and U.E.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel

    Ella Wilczynski & Uri Nevo

  2. School of Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel

    Efrat Sasson, Uzi Eliav & Gil Navon

  3. Sagol School of Neuroscience, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Uri Nevo

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  1. Ella Wilczynski
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Correspondence to Uri Nevo.

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All the authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. (approval # M-01-17-095).

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The research was carried out in accordance with the ethics declaration at the animal care unit of the Faculty of Medicine, Tel Aviv University (approval # M-01-17-095).

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Uzi Eliav: Died December 19th, 2019.

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Wilczynski, E., Sasson, E., Eliav, U. et al. An in vivo implementation of the MEX MRI for myelin fraction of mice brain. Magn Reson Mater Phy 35, 267–276 (2022). https://doi.org/10.1007/s10334-021-00950-z

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  • DOI: https://doi.org/10.1007/s10334-021-00950-z

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