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Published on: March 27, 2016
MRI characterization of paranodal junction failure and related spinal cord changes in mice
Morito Takano1, Keigo Hikishima, Kanehiro Fujiyoshi
1Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Abstract:
The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the paranodal junctions of the spinal cord in cerebroside sulfotransferase knock-out (CST-KO) mice. Here, we showed that high-resolution MRI and DTI characteristics can reflect paranodal junction failure in CST-KO mice. We found significantly lower T1 times and significantly higher T2 times in the spinal cord MRIs of CST-KO mice as compared to wild-type (WT) mice. Spinal cord DTI showed significantly lower axial diffusivity and significantly higher radial diffusivity in CST-KO mice as compared to WT mice. In contrast, the histological differences in the paranodal junctions of WT and CST-KO mice were so subtle that electron microscopy or immunohistological analyses were necessary to detect them. We also measured gait disturbance in the CST-KO mice, and determined the conduction latency by electrophysiology. These findings demonstrate the potential of using MRI and DTI to evaluate white matter disorders that involve paranodal junction failure.
Insights
High-resolution MRI and DTI can detect spinal cord paranodal junction failure in mice, offering a non-invasive method for evaluating white matter disorders. These imaging techniques revealed subtle structural changes not easily seen with histology alone.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Histopathology
Background:
- The paranodal junction is crucial for neuronal function in the central nervous system (CNS).
- Traditionally, detecting paranodal junction pathology required invasive histological methods.
- Diffusion tensor MRI (DTI) shows promise for assessing microstructural changes in CNS diseases.
Purpose of the Study:
- To investigate if Magnetic Resonance Imaging (MRI) and DTI can detect structural changes in spinal cord paranodal junctions.
- To evaluate these imaging techniques in cerebroside sulfotransferase knock-out (CST-KO) mice, a model for white matter disorders.
Main Methods:
- High-resolution MRI and DTI were performed on the spinal cords of CST-KO and wild-type (WT) mice.
- Quantitative MRI parameters (T1, T2 times) and DTI metrics (axial diffusivity, radial diffusivity) were analyzed.
- Histological and electrophysiological assessments were conducted for comparison.
Main Results:
- CST-KO mice exhibited significantly lower T1 times and higher T2 times in spinal cord MRIs compared to WT mice.
- Spinal cord DTI revealed significantly lower axial diffusivity and higher radial diffusivity in CST-KO mice.
- Histological differences were subtle, requiring electron microscopy or immunohistochemistry for detection.
Conclusions:
- High-resolution MRI and DTI can effectively detect paranodal junction failure in the spinal cord.
- These imaging modalities offer a sensitive, non-invasive approach to evaluate white matter disorders involving paranodal defects.
- Findings suggest MRI and DTI's potential for diagnosing and monitoring CNS white matter diseases.
