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Disappearing "T1 black holes" in an animal model of multiple sclerosis
Istvan Pirko1, Aaron Johnson, Jeff Gamez
1Department of Neurology, Mayo Clinic and Foundation, 200 First Street Southwest, Rochester, MN 55905, USA.
Abstract:
Brain MRI in multiple sclerosis (MS) frequently shows areas of hypointensity in the white matter on T1 weighted sequences ("T1 black holes"). These areas are thought to be consistent with irreversible axonal loss. In this study T1 black holes were characterized in Theiler's Murine Encephalitis Virus infection, an established model of demyelinating diseases in mice. The spectrum of TMEV is broad in different strains. C57BL/6J mice develop a self-limited brain disease, which resolves within 4-6 weeks. We followed six mice with serial MRI and MRS on days 0, 3,7,21 and 45. The studies were performed in a 7 Tesla magnet. Periventricular and parahippocampal T1 black holes seen as early as 3 days, with decreasing NAA/Cre ratio on MRS. The extent of pathology was most severe on days 3 and 7. T1 black holes are thought to be consistent with areas of irreversible axonal loss. This is challenged by our observations of resolution of T1 black holes by day 45. This was concomitant with the normalization of MRS findings in the areas of interest. We conclude that T1 black holes may represent a transient phenomenon in this model of MS. The recovery of these areas studied suggests an active repair mechanism.
Insights
T1 black holes in multiple sclerosis (MS) models may resolve over time. This study in mice suggests these lesions might be transient, indicating potential repair mechanisms in demyelinating diseases.
Area of Science:
- Neuroimaging
- Demyelinating Diseases
- Animal Models
Background:
- Multiple sclerosis (MS) brain MRI often reveals T1 hypointensities ("black holes"), presumed irreversible axonal loss.
- Theiler's Murine Encephalitis Virus (TMEV) infection in mice serves as a model for demyelinating diseases.
Purpose of the Study:
- To characterize T1 black holes in a TMEV mouse model.
- To investigate the reversibility of T1 black holes and associated pathology.
Main Methods:
- Serial 7 Tesla MRI and MRS were performed on C57BL/6J mice infected with TMEV.
- Measurements were taken on days 0, 3, 7, 21, and 45 post-infection.
Main Results:
- T1 black holes appeared early (day 3) in periventricular and parahippocampal regions.
- MRS showed a decreased NAA/Cre ratio, indicating neuronal/axonal damage.
- Lesion severity peaked around days 3-7.
- Remarkably, T1 black holes resolved by day 45, coinciding with MRS normalization.
Conclusions:
- T1 black holes in this MS mouse model may be transient, not solely indicative of irreversible axonal loss.
- The observed resolution suggests active repair mechanisms are involved in demyelinating disease recovery.
