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Early macrophage MRI of inflammatory lesions predicts lesion severity and disease development in relapsing EAE
B Brochet1, M S A Deloire, T Touil
1Université Victor Ségalen Bordeaux 2, EA2966-Neurobiologie des affections de la myéline, BP 78, 146 rue Léo Saignat, 33076 Bordeaux-cedex, France. bruno.brochet@chu-bordeaux.fr
Abstract:
Magnetic resonance imaging (MRI) is of great utility in diagnosis and monitoring of multiple sclerosis (MS). Axonal loss is considered the main cause of accumulating irreversible disability. MRI using ultrasmall-super-paramagnetic-iron-oxide (USPIO) nanoparticles is a new technique to disclose in vivo central nervous system (CNS) inflammatory lesions infiltrated by macrophages in experimental autoimmune encephalomyelitis (EAE). Here, we raised the question of whether USPIO-enhanced MRI could serve as a tool to predict disease severity. We investigated, in a relapsing EAE model with various degrees of disease severity, the interindividual differences at the beginning of CNS inflammation as revealed in vivo by MRI with USPIO in correlation to the severity of both acute and chronic tissue damage including axonal loss. At the onset of the disease, observation of MRI alterations with USPIO allowed assignment of animals into USPIO+ and USPIO- groups. In 54.5% of diseased rats, MRI with USPIO+ at first attack revealed signal abnormalities mainly localized in the brainstem and cerebellum. Although animals did not present any clinically significant differences during the first attack, USPIO+ rats presented significantly more important tissue alterations at the first attack (onset and initiated recovery phase) and, at the second attack, more severe clinical disease with axonal loss compared to USPIO- rats. MRI lesion load and volume at the first attack correlate significantly with inflammation, macrophage recruitment, demyelination, acute axonal damage and, at the second attack, extent of axonal loss. This new MRI application of in vivo monitoring of macrophage infiltration provides a new platform to investigate the severity of inflammatory demyelinating CNS diseases.
Insights
Ultrasmall-super-paramagnetic-iron-oxide (USPIO) enhanced MRI can predict multiple sclerosis (MS) disease severity by detecting early macrophage infiltration in the central nervous system (CNS). This technique correlates with tissue damage and axonal loss, offering a new diagnostic tool.
Area of Science:
- Neuroimaging
- Immunology
- Neurology
Background:
- Magnetic resonance imaging (MRI) is crucial for diagnosing and monitoring multiple sclerosis (MS).
- Axonal loss is the primary driver of irreversible disability in MS.
- Ultrasmall-super-paramagnetic-iron-oxide (USPIO) nanoparticles offer a novel MRI technique for visualizing macrophage-infiltrated inflammatory lesions in the central nervous system (CNS).
Purpose of the Study:
- To determine if USPIO-enhanced MRI can predict disease severity in experimental autoimmune encephalomyelitis (EAE), a model for MS.
- To investigate the correlation between early in vivo USPIO-enhanced MRI findings and the extent of tissue damage, including axonal loss.
Main Methods:
- A relapsing EAE model with varying disease severities was used.
- Animals were assessed using USPIO-enhanced MRI at the onset of CNS inflammation.
- MRI findings were correlated with clinical disease severity, tissue damage, macrophage infiltration, demyelination, and axonal loss.
Main Results:
- USPIO-enhanced MRI identified two groups of rats: USPIO+ (54.5% of diseased rats) and USPIO-.
- USPIO+ rats showed significantly more tissue alterations during the first attack and more severe clinical disease and axonal loss during the second attack compared to USPIO- rats.
- MRI lesion load and volume at the first attack correlated significantly with inflammation, macrophage recruitment, demyelination, and acute axonal damage, as well as later axonal loss.
Conclusions:
- USPIO-enhanced MRI can reveal interindividual differences in CNS inflammation at the disease onset.
- Early detection of macrophage infiltration via USPIO-enhanced MRI serves as a predictive marker for disease severity and axonal loss in inflammatory demyelinating CNS diseases.
- This MRI application provides a valuable platform for in vivo monitoring of macrophage infiltration and investigating disease progression.
