Cytoarchitecture of the mouse brain by high resolution diffusion magnetic resonance imaging

Nian Wang, Leonard E.White, Yi Qi, Gary Cofer, G. Allan Johnson

NeuroImage Volume 216, 1 August 2020, 116876  j.neuroimage.2020.116876

MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial resolution and various image contrasts derived from water relaxation or diffusion properties. Magnetic resonance histology has the potential to become an indispensable research tool to mitigate such challenges. In the present study, we acquired high spatial resolution MRI datasets, including diffusion MRI (dMRI) at 25 ​μm isotropic resolution and quantitative susceptibility mapping (QSM) at 21.5 ​μm isotropic resolution to validate with conventional mouse brain histology. Diffusion weighted images (DWIs) show better delineation of cortical layers and glomeruli in the olfactory bulb than fractional anisotropy (FA) maps. However, among all the image contrasts, including quantitative susceptibility mapping (QSM), T1/T2∗ images and DTI metrics, FA maps highlight unique laminar architecture in sub-regions of the hippocampus, including the strata of the dentate gyrus and CA fields of the hippocampus. The mean diffusivity (MD) and axial diffusivity (AD) yield higher correlation with DAPI (0.62 and 0.71) and NeuN (0.78 and 0.74) than with NF-160 (−0.34 and −0.49). The correlations between FA and DAPI, NeuN, and NF-160 are 0.31, −0.01, and −0.49, respectively. Our findings demonstrate that MRI at microscopic resolution deliver a three-dimensional, non-invasive and non-destructive platform for characterization of fine structural detail in both gray matter and white matter of the mouse brain.


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This work was supported by the NIH/NIBIB National Biomedical Technology Resource Center (P41 EB015897 to G. Allan Johnson), NIH 1S10OD010683-01 (to G. Allan Johnson), 1R01NS096720-01A1 (to G. Allan Johnson) and Charles E. Putman MD Vision Award of the Department of Radiology, Duke University School of Medicine (to Nian Wang and Charles E. Spritzer). The authors thank Tatiana Johnson for editorial comments on the manuscript. The authors thank James Cook and Lucy Upchurch for significant technical support.