Han : Diffusion magnetic resonance imaging and gene expression profiles during postnatal mouse brain development
Diffusion magnetic resonance imaging and gene expression profiles during postnatal mouse brain development
Department of Radiology and Imaging Sciences, Indiana University
Xinyue Han1 and Nian Wang1, 2
1 Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States
2 Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN, United States
The development of brain is a highly complex process that are orchestrated by the expression of numerous genes. Each distinct region of the brain exhibits unique transcriptome patterns that undergo dynamic changes throughout development, reflecting the progressive specialization of structures and functions. These spatio-temporal patterns coordinate the microstructural transformations occurring in the brain. Diffusion tensor imaging (DTI) is the most common approach for investigating brain microstructures based on the water diffusion properties.
In this study, we aimed to explore the correlation between DTI metrics and the spatio-temporal profiles of gene expression. We first conducted diffusion magnetic resonance imaging (dMRI) on wild-type mice at postnatal P4 and P14. Next, we extracted DTI metrics— axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD)—from each mouse using the diffusion tensor model. We selected 11 distinct regions-of-interest (ROIs) from DTI analysis. Subsequently, we analyzed spatio-temporal gene expression profiles by using expression density data of 2002 genes of interest at P4 and P14 from these 11 brain regions. Lastly, we statistically examined the correlation of DTI metrics with the gene expression density data.
We found that AD, FA, and MD exhibited decreasing values only in the “telencephalic vesicle” region from P4 to P14, while the other regions showed increasing values. As for RD, the “rostral secondary prosencephalon” and “prepontine hindbrain” regions had constant values while the others had increasing values. By using partial least squares (PLS) regression, we identified the first two PLS components that are negatively correlated to DTI.
We concluded that the brain tissue diffusion changes captured by DTI during postnatal development are associated with unique spatio-temporal gene expression profiles.
Translational/Human Health Impact:
This research contributes to our understanding of brain development and provides potential avenues for investigating neurodevelopmental disorders and neurodegenerative diseases using non-invasive imaging techniques.