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Neurite orientation dispersion and density imaging of mouse brain microstructure


Advanced biophysical models like neurite orientation dispersion and density imaging (NODDI) have been developed to estimate the microstructural complexity of voxels enriched in dendrites and axons for both in vivo and ex vivo studies. NODDI metrics derived from high spatial and angular resolution diffusion MRI using the fixed mouse brain as a reference template have not yet been reported due in part to the extremely long scan time required. In this study, we modified the three-dimensional diffusion-weighted spin-echo pulse sequence for multi-shell and undersampling acquisition to reduce the scan time. This allowed us to acquire several exhaustive datasets that would otherwise not be attainable. NODDI metrics were derived from a complex 8-shell diffusion (1000–8000 s/mm2) dataset with 384 diffusion gradient-encoding directions at 50 µm isotropic resolution. These provided a foundation for exploration of tradeoffs among acquisition parameters. A three-shell acquisition strategy covering low, medium, and high b values with at least angular resolution of 64 is essential for ex vivo NODDI experiments. The good agreement between neurite density index (NDI) and the orientation dispersion index (ODI) with the subsequent histochemical analysis of myelin and neuronal density highlights that NODDI could provide new insight into the microstructure of the brain. Furthermore, we found that NDI is sensitive to microstructural variations in the corpus callosum using a well-established demyelination cuprizone model. The study lays the ground work for developing protocols for routine use of high-resolution NODDI method in characterizing brain microstructure in mouse models.

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This work was supported by the NIH P41 EB015897 (to GA Johnson), NIH 1S10OD010683-01 (to GA Johnson), 1R01NS096720-01A1 (to GA Johnson). The authors thank James Cook and Lucy Upchurch for significant technical support. The authors thank Prof. Jie Zhuang for insight comments and discussions. The authors thank Tatiana Johnson for editorial comments on the manuscript. The authors thank NIEHS with histology help.

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Correspondence to Nian Wang or G. Allan Johnson.

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The authors declare no competing financial interests.

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All animal studies have been approved by the appropriate ethics committee: Duke University Institutional Animal Care and Use Committee.

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No human subject was used in this study.

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Wang, N., Zhang, J., Cofer, G. et al. Neurite orientation dispersion and density imaging of mouse brain microstructure. Brain Struct Funct 224, 1797–1813 (2019).

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  • Compressed sensing
  • Diffusion MRI
  • Demyelination
  • Cuprizone
  • Neurite density