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Updated: Jun 7, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Pathological basis of diffusely abnormal white matter: insights from magnetic resonance imaging and histology
Cornelia Laule1, Irene M Vavasour, Esther Leung
1Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada. claule@physics.ubc.ca
Background:
The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) has not been elucidated in detail, but may be an important element in disability and clinical progression.
Methods:
Fifty-three subjects with MS were examined with T₁, multi-echo T₂ and magnetization transfer (MT). Twenty-three samples of formalin-fixed MS brain tissue were examined with multi-echo T₂ and subsequently stained for myelin phospholipids using luxol fast blue, for axons using Bielschowsky, immunohistochemically for the myelin proteins myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3' phosphohydrolase (CNP) and for astrocytes using glial fibrillary acidic protein (GFAP). Regions of interest in DAWM were compared with normal appearing white matter.
Results:
Fourteen of 53 subjects with MS in the in vivo study showed the presence of DAWM. Subjects with DAWM were found to have a significantly lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD) when compared with subjects without DAWM (EDSS: 1.5 versus 3.0, p = 0.031; DD: 5.4 versus 10.3 years, p = 0.045). DAWM in vivo had reduced myelin water and MT ratio, and increased T₂ and water content. Histological analysis suggests DAWM, which shows a reduction of the myelin water fraction, is characterized by selective reduction of myelin phospholipids, but with a relative preservation of myelin proteins and axons.
Conclusions:
These findings suggest that the primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids that correlates with a reduction of the myelin water fraction.
Insights
Diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) is characterized by reduced myelin phospholipids, not axon or protein loss. This finding offers new insights into MS pathology and disability progression.
Area of Science:
- Neuroscience
- Pathology
- Radiology
Background:
- The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) remains unclear.
- DAWM may significantly contribute to disability and clinical progression in MS patients.
Purpose of the Study:
- To elucidate the pathological basis of DAWM in MS.
- To compare DAWM with normal-appearing white matter (NAWM) using advanced imaging and histological techniques.
Main Methods:
- In vivo MRI (T₁, multi-echo T₂, MT) and ex vivo histological analysis (luxol fast blue, Bielschowsky, immunohistochemistry for MBP, CNP, GFAP) were performed on MS brain tissue and subjects.
- Fifty-three MS subjects underwent in vivo imaging, and 23 MS brain tissue samples were analyzed histologically.
- Regions of interest in DAWM were compared with NAWM.
Main Results:
- Fourteen of 53 MS subjects exhibited DAWM.
- DAWM was associated with lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD).
- In vivo DAWM showed reduced myelin water and MT ratio, increased T₂ and water content, with histological analysis revealing selective reduction of myelin phospholipids but relative preservation of myelin proteins and axons.
Conclusions:
- The primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids.
- This phospholipid reduction correlates with a decreased myelin water fraction, offering a key insight into MS white matter changes.
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