Detecting early brain susceptibility changes before demyelination in cuprizone mouse model using quantitative...

Area of Science:

• Neuroimaging
• Neuropathology
• Biomarker Development

Background:

• Multiple Sclerosis (MS) is a central nervous system disease characterized by demyelination and inflammation.
• The cuprizone (CPZ) mouse model is crucial for studying MS-related demyelination and remyelination.
• Conventional MRI is sensitive to myelin changes, but quantitative susceptibility mapping (QSM) can also detect iron-related pathology.

Purpose of the Study:

• To evaluate the utility of longitudinal whole-brain multimodal MRI, including QSM, in the CPZ mouse model of MS.
• To assess QSM's sensitivity in detecting early demyelination and tracking dynamic changes in oligodendrocytes.
• To compare QSM's performance with conventional MRI techniques (T2-weighted imaging, Magnetization Transfer Imaging) in characterizing white matter injury.

Main Methods:

• Longitudinal multimodal MRI (T2-weighted, Magnetization Transfer Imaging, QSM) was performed on CPZ-treated mice.
• Imaging covered pre-demyelination, acute demyelination, chronic demyelination, and remyelination stages.
• Regional analysis focused on the corpus callosum (CC) and anterior commissure (AC), with histological validation.

Main Results:

• All MRI modalities detected demyelination, showing increased T2 signal, decreased MTR, and increased susceptibility, with partial recovery during remyelination.
• QSM uniquely identified susceptibility decreases at week 2, preceding apparent demyelination, indicating early oligodendrocyte dysfunction.
• Regional heterogeneity was observed, with the CC showing rapid changes and the AC exhibiting steadier alterations across disease phases.

Conclusions:

• QSM is a sensitive imaging biomarker for detecting early MS pathology and monitoring oligodendrocyte dynamics.
• QSM complements conventional MRI, enhancing the characterization of white matter injury in the CPZ model.
• QSM holds significant translational potential for monitoring MS progression and therapeutic responses in clinical settings.