Diffusion MRI quantifies early axonal loss in the presence of nerve swelling
Open accessAbstract
BACKGROUND: Magnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression. METHODS: Eight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed. RESULTS: In this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice. CONCLUSIONS: Our findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts.
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Demyelination is linked to myelin and oligodendrocyte loss, axon damage, active gliosis, and astrocytic hypertrophy.
“Demyelination is linked to myelin and oligodendrocyte loss, axon damage, active gliosis, and astrocytic hypertrophy (Lin et al. 2017; Zhang et al. 2012b; Nikic et al. 2011; Simons et al. 2014; Skripuletz et al. 2008).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Lin et al. 2017
The Results (Immunohistochemistry of optic nerve, Fig. 5; page not specified) report reduced myelin staining, axonal injury and loss, and cell infiltration in optic neuritis nerves. The paper does not establish oligodendrocyte loss, active gliosis, or astrocytic hypertrophy; its findings also concern optic neuritis rather than demyelination generally. (LLM, conf=0.87)
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Magnetic Resonance Imaging of the Monkey Fetal Brain In Utero
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Multimodal approaches to visual experimental research: Imaging, electrophysiology, and behavior
Zhong, J., Zhang, H., Li, J., & Zhou, H. (2026) · Experimental Eye Research · doi:10.1016/j.exer.2026.111241
- Authors
- Lin, T.-H., Chiang, C.-W., Perez-Torres, C. J., Sun, P., Wallendorf, M., Schmidt, R. E., Cross, A. H., & Song, S.-K.
- Affiliations
- Washington University in St. Louis (US)
- National Health Research Institutes (TW)
- Corresponding author
- Song, Sheng-Kwei
- Venue
- Journal of Neuroinflammation
- Published
- 2017-04-07
- Volume
- 14
- Issue
- 1
- Pages
- 78-78
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC5384143
- OpenAlex
- W2605355737
- Cited by
- 42
- References
- 50
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 2
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01-NS047592, P01-NS059560)
- National Eye Institute (U01- EY025500)
- National Multiple Sclerosis Society (RG 4549A4/1, RG-1507-05315)
- U.S. Department of Defense (W81XWH-12-1-0457)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- axonal loss, diffusion basis spectrum imaging, optic neuritis, experimental autoimmune encephalomyelitis, optic nerve swelling, demyelination, multiple sclerosis, visual acuity, longitudinal biomarkers, C57BL/6 mice, white matter pathology
- MeSH terms
- Animals, Axons, Female, Mice, Inbred C57BL, Optic Nerve, Optic Neuritis, Diffusion Magnetic Resonance Imaging, Mice
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