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Updated: Mar 16, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Diffusivity in multiple sclerosis lesions: At the cutting edge?
Alexander Klistorner1, Chenyu Wang2, Vera Fofanova3
1Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Background:
Radial Diffusivity (RD) has been suggested as a promising biomarker associated with the level of myelination in MS lesions. However, the level of RD within the lesion is affected not only by loss of myelin sheaths, but also by the degree of tissue destruction. This may lead to exaggeration of diffusivity measures, potentially masking the effect of remyelination.
Objective:
To test the hypothesis that the T2 hyperintense lesion edge that extends beyond the T1 hypointense lesion core is less affected by tissue loss, and therefore a more appropriate target for imaging biomarker development targeting de- and re-myelination.
Method:
Pre- and post-gadolinium (Gd) enhanced T1, T2 and DTI images were acquired from 75 consecutive RRMS patients. The optic radiation (OR) was identified in individual patients using a template-based method. T2 lesions were segmented into T1-hypointense and T1-isointense areas and lesion masks intersected with the OR. Average Radial, Axial and Mean diffusivity (RD, AD and MD) and fractional anisotropy (FA) were calculated for lesions of the entire brain and the OR. In addition, Gd enhancing lesions were excluded from the analysis.
Results:
86% of chronic T2 lesions demonstrated hypointense areas on T1-weighted images, which typically occupied the central part of each T2 lesion, taking about 40% of lesional volume. The T1-isointense component of the T2 lesion was most commonly seen as a peripheral ring of relatively constant thickness ("T2-rim"). While changes of diffusivity between adjacent normal appearing white matter and the "T2-rim" demonstrated a disproportionally high elevation of RD compare to AD, the increase of water diffusion was largely isointense between the "T2-rim" and T1-hypointense parts of the lesion.
Conclusion:
Distinct patterns of diffusivity within the central and peripheral components of MS lesions suggest that axonal loss dominates in the T1 hypointense core. The effects of de/remyelination may be more readily detected in the "T2-rim", where there is relative preservation of structural integrity. Identifying and separating those patterns has an important implication for clinical trials of both neuroprotective and, in particular, remyelinating agents.
Insights
Radial diffusivity (RD) in MS lesions is affected by tissue destruction, masking remyelination. The T2 lesion edge, less affected by tissue loss, is a better target for imaging biomarkers of de- and remyelination.
Area of Science:
- Neuroimaging
- Biomarker Development
- Multiple Sclerosis Research
Background:
- Radial diffusivity (RD) is a potential biomarker for myelination in MS lesions.
- However, RD is influenced by both myelin loss and tissue destruction, potentially obscuring remyelination effects.
Purpose of the Study:
- To investigate if the T2 lesion edge (T1-isointense rim) is a more suitable region than the T1-hypointense core for imaging biomarkers of de- and remyelination.
- Hypothesizing that the T2 lesion edge is less affected by tissue loss.
Main Methods:
- Diffusion tensor imaging (DTI) and contrast-enhanced T1/T2 MRI were acquired from 75 RRMS patients.
- T2 lesions were segmented into T1-hypointense (core) and T1-isointense (rim) areas.
- Diffusivity metrics (RD, AD, MD) and FA were calculated for lesion components, excluding enhancing lesions.
Main Results:
- Chronic T2 lesions predominantly featured a T1-hypointense core (approx. 40% volume) and a peripheral T1-isointense "T2-rim".
- The "T2-rim" showed a disproportionately higher increase in RD compared to AD relative to normal white matter.
- Diffusivity increases were similar between the "T2-rim" and the T1-hypointense core.
Conclusions:
- Distinct diffusivity patterns suggest axonal loss dominates the T1-hypointense lesion core.
- The "T2-rim" may better reflect de/remyelination due to preserved structural integrity.
- Separating these lesion components is crucial for evaluating neuroprotective and remyelinating therapies in MS clinical trials.
