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Magnetic resonance imaging of experimental allergic encephalomyelitis in primates
W A Stewart1, E C Alvord, S Hruby
1MRI Facility, University of Guelph, Ontario, Canada.
Abstract:
The potential use of quantitative MRI to characterize early, as well as late, immune-mediated lesions of multiple sclerosis (MS) has been investigated. Experimental allergic encephalomyelitis (EAE) was induced in 4 male Macaca fascicularis monkeys, and the development of the disease followed using quantitative MRI at 0.15 Tesla. Serial scans were recorded daily, beginning at day 9 after inoculation. Lesions were detected before the onset of clinical signs, due to an elevation in the spin-lattice (T1) and spin-spin (T2) relaxation times. The T1 and T2 values from the lesions were shown to increase over time, indicative of progressive change at a molecular level. The appearance of any new lesions and any changes in existing ones were noted; this allowed dating of the lesions postmortem. Pathological correlation showed the long T1 and T2 values to be associated with the presence of inflammation, demyelination and haemorrhagic necrosis. Microscopically similar lesions had the same MRI characteristics. In addition, these studies showed the oldest lesions to be the most haemorrhagic; this is contrary to the belief that haemorrhage is a secondary event in EAE. The results show that quantitative MRI is sensitive to variable pathology, and has the potential for use in characterizing the pathological progression in MS.
Insights
Quantitative MRI can detect early multiple sclerosis (MS) lesions before symptoms appear. This imaging technique shows promise for tracking disease progression by revealing inflammation and tissue changes.
Area of Science:
- Neuroimaging
- Pathology
Background:
- Multiple sclerosis (MS) is an immune-mediated disease affecting the central nervous system.
- Characterizing MS lesions, particularly early and late stages, is crucial for understanding disease progression.
Purpose of the Study:
- To investigate the utility of quantitative magnetic resonance imaging (MRI) for characterizing immune-mediated lesions in multiple sclerosis (MS).
- To correlate MRI findings with pathological changes in an animal model of MS.
Main Methods:
- Experimental allergic encephalomyelitis (EAE), an MS model, was induced in non-human primates (Macaca fascicularis).
- Quantitative MRI at 0.15 Tesla was used for daily serial scans starting on day 9 post-inoculation.
- Lesion characteristics, including T1 and T2 relaxation times, were monitored and correlated with postmortem histopathology.
Main Results:
- Lesions were detected via elevated T1 and T2 relaxation times before clinical signs, indicating early disease detection.
- Increasing T1 and T2 values over time suggested progressive molecular changes within lesions.
- Pathological correlation confirmed that elevated T1 and T2 values corresponded to inflammation, demyelination, and hemorrhagic necrosis.
- Older lesions exhibited greater hemorrhage than previously believed, challenging existing EAE models.
Conclusions:
- Quantitative MRI is sensitive to diverse pathological features in MS lesions.
- The technique holds potential for characterizing the pathological progression of multiple sclerosis (MS).
- MRI findings can provide insights into the temporal evolution of lesion pathology, including hemorrhage.