Diffusion kurtosis imaging, MAP-MRI and NODDI selectively track gray matter myelin density in the primate cerebral cortex
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Abstract
Diffusion magnetic resonance imaging (dMRI) has been widely used to model the trajectory of myelinated fiber bundles in the white matter. Increasingly, it is also used to evaluate the microstructure of the cerebral cortex gray matter. For example, in diffusion tensor imaging (DTI) of the cortex, fractional anisotropy (FA) correlates strongly with the anisotropy of cellular anatomy, while radial diffusivity (RD) tracks the anisotropy of myelinated fibers. However, no DTI parameter shows specificity to gray matter myelin density. Here, we show that three higher-order diffusion parameters—the mean diffusion kurtosis (MK), the Neurite Density Index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the Non-Gaussian (NG) parameter from mean apparent propagator (MAP)-MRI—each track the laminar and regional myelin density of the primate cerebral cortex in fine detail. We carried out ultra-high-resolution, multi-shelled dMRI in ex-vivo marmoset monkey brains. We compared the spatial mapping of the MK, NDI, and ND diffusion parameters to the cortical myelin distribution of these brains, with the latter obtained in two ways: First, using histological sections finely co-registered to the MRI, and second using magnetization transfer ratio MRI scans (MTR), an established non-diffusion method for imaging myelin density. We found that, in contrast to DTI parameters, each of these higher-order diffusion measures captured the spatial variation of myelin density in the cortex. The demonstration that diffusion parameters exhibit both sensitivity and specificity for gray matter myelin density will allow dMRI to more effectively track human disease, in which myelinated and non-myelinated tissue compartments are affected differentially.
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A relationship between mean kurtosis and cortical myelin content has been reported in primates.
“A relationship between mean kurtosis and cortical myelin content has been reported in primates (Reveley et al., 2024);”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Reveley et al., 2024
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Wang, W., Wen, X., Zhang, Y., Wang, H., Hu, L., Tan, C., & Liu, Z. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1924031
Microstructural maturation of the adult mouse brain
Rahman, N., Hamilton, J., Xu, K., Brown, A. M., & Baron, C. A. (2025) · Communications Biology · doi:10.1038/s42003-025-08981-1 · Cited by 1 · see citing works
Analysis of cortical dysplasias using b-tensor encoding diffusion MRI in an animal model
Ortega-Fimbres, O., Ríos-Carrillo, R., Gaspar-Martínez, E., Ruiz-Acosta, P., Regalado, M., Luna‐Munguía, H., Ramírez-Manzanares, A., & Concha, L. (2026) · PLoS ONE · doi:10.1371/journal.pone.0346132
High‐Resolution Diffusion Kurtosis Imaging of Hippocampus Subfields Across the Healthy Lifespan
Stack-Sánchez, P., Gross, D. W., Khan, A. R., & Beaulieu, C. (2026) · NMR in Biomedicine · doi:10.1002/nbm.70355
Kashida, N., Yamamuro, K., Matsuoka, K., Mizui, R., Ishida, R., Takeda, T., Tamakoshi, H., Yoshihara, T., Takahashi, M., Yamauchi, T., et al. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1688324
Graph-Based White Matter Tractometry: Methods, Applications, and the Path to Validation
Li, J., Zhang, C., Wan, Z., Xie, Y., Zhang, H., Liu, X., & Wu, Y. N. (2026) · Neuroinformatics · doi:10.1007/s12021-026-09804-2
Diffusion MRI of gray matter microstructural profiles in healthy aging
Merenstein, J. L. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106896
Highly replicable multisite patterns of adolescent white matter maturation
Meisler, S. L., Cieslak, M., Bagautdinova, J., Hendrickson, T. J., Pandhi, T., Chen, A. A., Hillman, N., Radhakrishnan, H., Salo, T., Feczko, E., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.09.021 · Cited by 1 · see citing works
- Authors
- Reveley, C., Ye, F. Q., & Leopold, D. A.
- Affiliations
- John Radcliffe Hospital (GB)
- National Institutes of Health (US)
- Corresponding author
- Reveley, Colin
- Venue
- Imaging Neuroscience
- Publisher
- MIT Press
- Published
- 2024
- Volume
- 2
- ISSN
- 2837-6056 (ISSN-L)
- PMC
- PMC12315753
- OpenAlex
- W4403823336
- Cited by
- 14
- References
- 87
- Citations by year
- 2026: 10 · 2025: 4
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Imaging Neuroscience (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- Funders
- National Institute of Mental Health (ZIAMH002786, ZICMH002899)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Physics and Astronomy › Nuclear and High Energy Physics › NMR spectroscopy and applications
- Keywords
- diffusion kurtosis imaging, NODDI, neurite density index, non-Gaussian diffusion, cerebral cortex, marmoset monkey, magnetization transfer ratio, cortical myelination, cortical microstructure
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