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Updated: Dec 9, 2025
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Published on: September 21, 2021
Ultrahigh-resolution MRI Reveals Extensive Cortical Demyelination in a Nonhuman Primate Model of Multiple Sclerosis
Maxime Donadieu1, Hannah Kelly1, Diego Szczupak2
1Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechanisms leading to brain damage. This study aimed to characterize cortical lesions in marmosets with EAE using ultrahigh-field (7 T) MRI and histological analysis. Tissue preparation was optimized to enable the acquisition of high-spatial resolution (50-μm isotropic) T2*-weighted images. A total of 14 animals were scanned in this study, and 70% of the diseased animals presented at least one cortical lesion on postmortem imaging. Cortical lesions identified on MRI were verified with myelin proteolipid protein immunostaining. An optimized T2*-weighted sequence was developed for in vivo imaging and shown to capture 65% of cortical lesions detected postmortem. Immunostaining confirmed extensive demyelination with preserved neuronal somata in several cortical areas of EAE animals. Overall, this study demonstrates the relevance and feasibility of the marmoset EAE model to study cortical lesions, among the most important yet least understood features of MS.
Insights
Detecting cortical lesions in multiple sclerosis (MS) is challenging. This study used advanced MRI in a marmoset model to visualize these lesions, aiding MS research.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Cortical lesions are a key cause of disability in multiple sclerosis (MS).
- Noninvasive in vivo magnetic resonance imaging (MRI) detection of these lesions is difficult.
- The common marmoset experimental autoimmune encephalomyelitis (EAE) model offers insights into MS pathophysiology.
Purpose of the Study:
- To characterize cortical lesions in marmosets with EAE using ultrahigh-field (7T) MRI.
- To correlate MRI findings with histological analysis.
- To assess the utility of the marmoset EAE model for studying MS cortical pathology.
Main Methods:
- High-spatial resolution (50-μm isotropic) T2*-weighted imaging at 7T MRI.
- Optimized tissue preparation for postmortem imaging.
- Myelin proteolipid protein immunostaining for histological verification.
Main Results:
- 70% of EAE marmosets showed cortical lesions on postmortem imaging.
- An optimized T2*-weighted MRI sequence detected 65% of postmortem lesions in vivo.
- Histology confirmed demyelination in cortical areas with preserved neurons.
Conclusions:
- The marmoset EAE model is relevant and feasible for studying MS cortical lesions.
- Ultrahigh-field MRI can visualize cortical lesions in this model.
- This approach advances understanding of poorly understood MS features.
