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Relationship between regional volume changes and water diffusion in fixed marmoset brains: an in vivo and ex vivo
Daisuke Yoshimaru1,2,3,4,5,6, Tomokazu Tsurugizawa2,3,4, Naoya Hayashi2,7,5
1Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Abstract:
Ex vivo studies of the brain are often employed as experimental systems in neuroscience. In general, brains for ex vivo MRI studies are usually fixed with paraformaldehyde to preserve molecular structure and prevent tissue destruction during long-term storage. As a result, fixing brain tissue causes microstructural changes and a decrease in brain volume. Therefore, the purpose of this study was to investigate the regional effect of brain volume and microstructural changes on the restricted diffusion of water molecules in the common marmoset brain using in vivo and ex vivo brains from the same individual. We used 9.4T magnetic resonance imaging and also compared the T2-weighted images and diffusion-weighted imaging (DWI) data between in vivo and ex vivo brains to investigate changes in brain volume and diffusion of water molecules in 12 common marmosets. We compared fractional anisotropy, mean diffusivity, AD (axial diffusivity), and radial diffusivity values in white matter and gray matter between in vivo and ex vivo brains. We observed that AD showed the strongest correlation with regional volume changes in gray matter. The results showed a strong correlation between AD and changes in brain volume. By comparing the in vivo and ex vivo brains of the same individual, we identified significant correlations between the local effects of perfusion fixation on microstructural and volumetric changes of the brain and alterations in the restricted diffusion of water molecules within the brain. These findings provide valuable insights into the complex relationships between tissue fixation, brain structure, and water diffusion properties in the marmoset brain.
Insights
Brain tissue fixation for ex vivo MRI studies alters brain volume and microstructure. Axial diffusivity (AD) strongly correlates with these regional volume changes, impacting water diffusion in marmoset brains.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Comparative Anatomy
Background:
- Ex vivo brain studies are crucial in neuroscience research.
- Paraformaldehyde fixation is standard for preserving brain tissue but causes microstructural changes and volume reduction.
- Understanding these fixation-induced alterations is vital for accurate interpretation of ex vivo MRI data.
Purpose of the Study:
- To investigate how brain volume and microstructural changes due to fixation affect water molecule diffusion.
- To examine the regional effects of fixation on diffusion metrics in the common marmoset brain.
- To compare in vivo and ex vivo MRI data from the same individuals to isolate fixation effects.
Main Methods:
- Utilized 9.4T magnetic resonance imaging (MRI) on 12 common marmosets.
- Acquired and compared T2-weighted and diffusion-weighted imaging (DWI) data from in vivo and ex vivo brains.
- Analyzed fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity in white and gray matter.
Main Results:
- Axial diffusivity (AD) demonstrated the strongest correlation with regional gray matter volume changes.
- A significant correlation was observed between AD and overall brain volume alterations post-fixation.
- Identified significant links between perfusion fixation, microstructural/volumetric brain changes, and altered water diffusion.
Conclusions:
- Perfusion fixation significantly impacts brain volume and microstructure, consequently altering water diffusion properties.
- Axial diffusivity (AD) is a sensitive indicator of fixation-induced volumetric changes in gray matter.
- These findings highlight the importance of considering fixation artifacts when interpreting ex vivo marmoset brain MRI data.
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