Related Experiment Video
Updated: Sep 11, 2025
Diffusion Imaging in the Rat Cervical Spinal Cord
Published on: April 7, 2015
Diffusion kurtosis imaging, MAP-MRI and NODDI selectively track gray matter myelin density in the primate cerebral
Colin Reveley1, Frank Q Ye2, David A Leopold2,3
1Wellcome Centre for Integrative Neuroimaging, Centre for fMRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Headington, Oxford, United Kingdom.
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.
Insights
Higher-order diffusion MRI parameters like mean diffusion kurtosis (MK) and Neurite Density Index (NDI) can specifically map gray matter myelin density in the brain. This advance improves diffusion MRI
Area of Science:
- Neuroimaging
- Biophysics
- Neuroanatomy
Background:
- Diffusion magnetic resonance imaging (dMRI) models white matter tracts and increasingly probes gray matter microstructure.
- Conventional diffusion tensor imaging (DTI) parameters lack specificity for gray matter myelin density.
- Myelin density is crucial for understanding brain function and disease.
Purpose of the Study:
- To investigate if higher-order dMRI parameters can specifically map gray matter myelin density.
- To compare the sensitivity and specificity of higher-order diffusion parameters against DTI metrics for myelin imaging.
- To validate diffusion parameter mapping against histological and established myelin imaging techniques.
Main Methods:
- Ultra-high-resolution, multi-shelled dMRI was performed on ex-vivo marmoset monkey brains.
- Three higher-order diffusion parameters were analyzed: mean diffusion kurtosis (MK), Neurite Density Index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the Non-Gaussian (NG) parameter from MAP-MRI.
- Cortical myelin distribution was assessed using histology and magnetization transfer ratio (MTR) MRI.
Main Results:
- MK, NDI, and NG parameters demonstrated high spatial correlation with cortical myelin density.
- Unlike DTI parameters (FA, RD), these higher-order measures specifically tracked laminar and regional myelin variations.
- The diffusion parameter mapping aligned well with both histological myelin stains and MTR-based myelin quantification.
Conclusions:
- Higher-order diffusion MRI parameters show sensitivity and specificity for mapping gray matter myelin density.
- This finding expands the utility of dMRI for studying brain microstructure, particularly in diseases affecting myelin.
- Advanced dMRI techniques offer a non-invasive window into myelin changes in both gray and white matter.
