Related Experiment Video
Updated: Jun 25, 2026
Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis
Published on: February 23, 2024
Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal
Matthew D Budde1, Mingqiang Xie, Anne H Cross
1Department of Radiology, Washington University, St. Louis, Missouri 63110, USA.
Abstract:
The dissociation between magnetic resonance imaging (MRI) and permanent disability in multiple sclerosis (MS), termed the clinicoradiological paradox, can primarily be attributed to the lack of specificity of conventional, relaxivity-based MRI measurements in detecting axonal damage, the primary pathological correlate of long-term impairment in MS. Diffusion tensor imaging (DTI) has shown promise in specifically detecting axonal damage and demyelination in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). To quantify the specificity of DTI in detecting axonal injury, in vivo DTI maps from the spinal cords of mice with EAE and quantitative histological maps were both registered to a common space. A pixelwise correlation analysis between DTI parameters, histological metrics, and EAE scores revealed a significant correlation between the water diffusion parallel to the white matter fibers, or axial diffusivity, and EAE score. Furthermore, axial diffusivity was the primary correlate of quantitative staining for neurofilaments (SMI31), markers of axonal integrity. Both axial diffusivity and neurofilament staining were decreased throughout the entire white matter, not solely within the demyelinated lesions seen in EAE. In contrast, although anisotropy was significantly correlated with EAE score, it was not correlated with axonal damage. The results demonstrate a strong, quantitative relationship between axial diffusivity and axonal damage and show that anisotropy is not specific for axonal damage after inflammatory demyelination.
Insights
Diffusion tensor imaging (DTI) shows axial diffusivity, a measure of water diffusion, accurately detects axonal damage in multiple sclerosis (MS) models. This finding helps explain the clinicoradiological paradox in MS by identifying specific markers of nerve damage.
Area of Science:
- Neuroimaging
- Neuroscience
- Pathology
Background:
- The clinicoradiological paradox in multiple sclerosis (MS) arises from conventional MRI's inability to detect axonal damage, the main cause of permanent disability.
- Diffusion tensor imaging (DTI) offers potential for specifically identifying axonal injury and demyelination in MS and its animal model, experimental autoimmune encephalomyelitis (EAE).
Purpose of the Study:
- To quantify the specificity of DTI in detecting axonal injury in the context of inflammatory demyelination.
- To establish a quantitative relationship between DTI parameters and histological markers of axonal damage.
Main Methods:
- In vivo DTI maps of mouse spinal cords with EAE were acquired and registered to a common space with quantitative histological maps.
- Pixelwise correlation analysis was performed between DTI parameters (axial diffusivity, anisotropy), histological metrics (neurofilament SMI31 staining), and EAE scores.
Main Results:
- Axial diffusivity showed a significant correlation with EAE scores and was the primary correlate of neurofilament staining, a marker of axonal integrity.
- Both axial diffusivity and neurofilament staining were reduced throughout the white matter, not just in demyelinated lesions.
- Anisotropy correlated with EAE score but not with axonal damage, indicating a lack of specificity.
Conclusions:
- Axial diffusivity is a specific and quantitative MRI marker for detecting axonal damage in inflammatory demyelination.
- DTI, particularly axial diffusivity, can help resolve the clinicoradiological paradox in MS by specifically measuring axonal injury.
