RESEARCH ARTICLE


Analysis of Brain Structure and Neural Organization in Dystrophin-Deficient Model Mice with Magnetic Resonance Imaging at 7 T



Mitsuki Rikitake1, Junichi Hata1, 2, *, Mayu Iida1, Fumiko Seki3, Rina Ito1, Yuji Komaki3, Chihoko Yamada3, Daisuke Yoshimaru2, Hirotaka James Okano2, Takako Shirakawa1
1 Graduate School of Human Health Sciences, Tokyo Metropolitan University, 7-2-10, Higashi-Ogu, Arakawa-ku,, Tokyo, Japan
2 Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
3 Live Animal Imaging Center, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Japan


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Creative Commons License
© 2022 Rikitake et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Division of Human Health Science, Department of Radiation Science, Tokyo Metropolitan University, 7-2-10 Higashi-Ogu, Arakawa-ku, Tokyo 116-8551, Japan; Tel: 03-3819-1211; E-mail: j-hata@tmu.ac.jp


Abstract

Background:

Dystrophin strengthens muscle cells; however, in muscular dystrophy, dystrophin is deficient due to an abnormal sugar chain. This abnormality occurs in skeletal muscle and in brain tissue.

Objective:

This study aimed to non-invasively analyze the neural organization of the brain in muscular dystrophy. We used a mouse model of muscular dystrophy to study whether changes in brain structure and neurodegeneration following dystrophin deficiency can be assessed by 7T magnetic resonance imaging.

Methods:

C57BL/10-mdx (X chromosome-linked muscular dystrophy) mice were used as the dystrophic mouse model and healthy mice were used as controls. Ventricular enlargement is one of the most common brain malformations in dystrophin-deficient patients. Therefore, we examined whether ventricular enlargement was observed in C57BL/10-mdx using transverse-relaxation weighted images. Brain parenchyma analysis was performed using diffusion MRI with diffusion tensor images and neurite orientation dispersion and density imaging. Parenchymal degeneration was assessed in terms of directional diffusion, nerve fiber diffusion, and dendritic scattering density.

Results:

For the volume of brain ventricles analyzed by T2WI, the average size was 1.5 times larger in mdx mice compared to control mice. In the brain parenchyma, a significant difference (p < 0.05) was observed in parameters indicating disturbances in the direction of nerve fibers and dendritic scattering density in the white matter region.

Conclusion:

Our results show that changes in brain structure due to dystrophin deficiency can be assessed in detail without tissue destruction by combining diffusion tensor images and neurite orientation dispersion and density imaging analyses.

Keywords: Muscular dystrophy, Dystrophin, Magnetic resonance imaging, Neurite orientation dispersion, Density imaging, Diffusion weighted imaging.