MRI-based morphometric structural changes correlate with histopathology in experimental autoimmune encephalomyelitis
Anna Lowinski1, Andreas Dabringhaus2, Matthias Kraemer3
1Institute of Neuroanatomy, Faculty of Medicine, University of Bonn and University Hospital Bonn, Nussallee 10, 53115 Bonn, Germany.
Background And Objectives:
Magnetic resonance imaging (MRI) and neurohistopathology are important correlates for evaluation of disease progression in multiple sclerosis (MS). Here we used experimental autoimmune encephalomyelitis (EAE) as an animal model of MS to determine the correlation between clinical EAE severity, MRI and histopathological parameters.
Methods:
N = 11 female C57BL/6J mice were immunized with human myelin oligodendrocyte glycoprotein 1-125, while N = 9 remained non-immunized. Mice were scanned longitudinally over a period of 13 weeks using a 11.7 Tesla (T) Bruker BioSpec® preclinical MRI instrument, and regional volume changes of the lumbar spinal cord were analyzed using Voxel-Guided Morphometry (VGM). Following the final in vivo T1-weighted MRI scan, the lumbar spinal cord of each mouse was subjected to an ex vivo MRI scan using T1-, T2*- and diffusion tensor imaging (DTI)-weighted sequences. Tissue sections were then stained for immune cell infiltration, demyelination, astrogliosis, and axonal damage using hematoxylin-eosin staining and immunohistochemistry.
Results:
While in vivo MRI VGM detected an overall increase in volume over time, no differences were observed between EAE animals and controls. Ex vivo MRI showed a generalized atrophy of the spinal cord, which was pronounced in the anterolateral tract. The most striking correlation was observed between EAE score, white matter atrophy in ex vivo T1-weighted scans and histological parameters.
Discussion:
The data demonstrate that ex vivo MRI is a valuable tool to assess white matter atrophy in EAE, which was shown to be directly linked to the severity of EAE and spinal cord histopathology.
Insights
Ex vivo MRI effectively detects spinal cord white matter atrophy in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. This atrophy strongly correlates with disease severity and neurohistopathology findings.
Area of Science:
- Neuroscience
- Medical Imaging
- Immunology
Background:
- Multiple sclerosis (MS) progression is evaluated using MRI and neurohistopathology.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for MS research.
Purpose of the Study:
- To correlate clinical EAE severity with MRI and histopathological parameters.
- To evaluate ex vivo MRI as a tool for assessing white matter atrophy in EAE.
Main Methods:
- 11 female C57BL/6J mice were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce EAE; 9 served as controls.
- Longitudinal in vivo MRI was performed over 13 weeks, followed by ex vivo MRI (T1, T2*, DTI) of the spinal cord.
- Histopathology included staining for immune cell infiltration, demyelination, astrogliosis, and axonal damage.
Main Results:
- In vivo MRI showed no significant volume differences between EAE and control groups.
- Ex vivo MRI revealed generalized spinal cord atrophy in EAE mice, particularly in the anterolateral tract.
- A strong correlation was found between EAE score, white matter atrophy on ex vivo MRI, and histopathological damage.
Conclusions:
- Ex vivo MRI is a valuable method for quantifying white matter atrophy in the EAE model.
- The observed atrophy is directly linked to EAE severity and spinal cord histopathology.
- This study highlights the utility of ex vivo MRI in understanding MS pathology.
