Related Experiment Video
Updated: Jul 20, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Quantitative MRI-pathology correlations of brain white matter lesions developing in a non-human primate model of
Erwin L A Blezer1, Jan Bauer, Herbert P M Brok
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands. blezer@invivonmr.uu.nl
Abstract:
Experimental autoimmune encephalomyelitis (EAE) induced with recombinant human myelin/oligodendrocyte glycoprotein in the common marmoset is a useful preclinical model of multiple sclerosis in which white matter lesions can be well visualized with MRI. In this study we characterized lesion progression with quantitative in vivo MRI (4.7 T; T(1) relaxation time +/- Gd-DTPA; T(2) relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains; T(1) and T(2) relaxation times; MTR) and histology. The histopathological characterization included axonal density measurements and the numeric quantification of infiltrated macrophages expressing markers for early active [luxol fast blue (LFB) or migration inhibition factor-related protein-14 positive] or late active/inactive [periodic acid Schiff (PAS) positive] demyelinating lesion. MRI experiments were done every two weeks until the monkeys were sacrificed with severe EAE-related motor deficits. Compared with the normal appearing white matter, lesions showed an initial increase in T(1) relaxation times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement of lesions was associated with stabilized T(1) values, while T(2) initially increased and stabilized thereafter and MTR remained decreased. Gd-DTPA leakage was highly variable throughout the experiment. MRI characteristics of the cortex and (normal appearing) white matter did not change during the experiment. We observed that in vivo MTR values correlated positively with the number of early active (LFB+) and negatively with late active (PAS+) macrophages. Ex vivo MTR and relaxation times correlated positively with the number of PAS-positive macrophages. None of the investigated MRI parameters correlated with axonal density.
Insights
This study used advanced MRI to track white matter lesions in a preclinical model of multiple sclerosis (MS). Findings reveal how MRI signals change with lesion progression, aiding MS research.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Experimental autoimmune encephalomyelitis (EAE) in marmosets is a valuable preclinical model for multiple sclerosis (MS).
- White matter lesions in EAE are detectable using magnetic resonance imaging (MRI).
Purpose of the Study:
- To characterize lesion progression in EAE using quantitative in vivo and ex vivo MRI.
- To correlate MRI findings with histopathological markers of demyelination and inflammation.
Main Methods:
- Quantitative in vivo MRI (4.7 T) including T1, T2 relaxation times, and magnetization transfer ratio (MTR) imaging.
- Ex vivo MRI of formaldehyde-fixed brains.
- Histopathological analysis including macrophage quantification (LFB+, PAS+) and axonal density measurements.
Main Results:
- EAE lesions showed increased T1, Gd-DTPA leakage, and decreased MTR in vivo.
- Lesion progression stabilized T1 values, increased T2, and maintained decreased MTR.
- In vivo MTR correlated with early active macrophages (LFB+), while ex vivo MTR and relaxation times correlated with late active/inactive macrophages (PAS+).
- No MRI parameters correlated with axonal density.
Conclusions:
- Quantitative MRI effectively tracks lesion evolution in the marmoset EAE model.
- MRI parameters reflect distinct stages of demyelination and macrophage infiltration.
- This model and imaging approach advance understanding of MS pathogenesis and therapeutic monitoring.
