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Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)
Abstract
A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation.
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“A previous DTI study also demonstrated that diffusivity maps can be used to delineate cell-dense regions such as the granule cell layer55”
From A spatial imaging-transcriptomics paradigm for deciphering the molecular basis of microscopic MRI in the normal brain and Alzheimer’s disease (2025) · cites this paper as [37]
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Callow, D. D., Won, J., Pena, G. S., Jordan, L. S., Arnold-Nedimala, N. A., Kommula, Y., Nielson, K. A., & Smith, J. C. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.645258 · Cited by 27
Shen, Y., Shen, Y., Wang, M., Jin, K., Yang, P., Cao, Z., Zhu, Q., Zhao, Z., Li, H., Han, L., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116073 · Cited by 16
Metadata
- Authors
- Stolp, H. B., Ball, G., So, P.-W., Tournier, J.-D., Jones, M., Thornton, C., & Edwards, A. D.
- Venue
- Scientific Reports
- Published
- 2018-03-05
- Volume
- 8
- Issue
- 1
- ISSN
- 2045-2322
- PMC
- PMC5838167
- Cited by
- 59
- References
- 9
- Language
- en
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