Extra-axonal restricted diffusion as an in-vivo marker of reactive microglia

Area of Science:

• Neuroscience
• Medical Imaging
• Pathology

Background:

• Reactive microgliosis is a key feature of neuroinflammation in various brain diseases.
• Current in-vivo mapping of reactive microglia using PET scans is limited by resolution, cost, and availability.
• Diffusion compartment imaging (DCI) offers potential for in-vivo microstructure analysis using MRI.

Purpose of the Study:

• To demonstrate the potential of DCI for mapping reactive microglia in vivo.
• To establish an MRI-based marker for reactive microgliosis.
• To explore DCI's utility in understanding neuroinflammatory disease pathogenesis.

Main Methods:

• Longitudinal DCI was performed in rats following dorsal root axotomy to induce Wallerian degeneration and microglial activation.
• Histology with Iba-1 immunostaining was used to quantify microglial density post-DCI.
• Analysis focused on the fraction of extra-axonal restricted diffusion measured by DCI.

Main Results:

• The fraction of extra-axonal restricted diffusion showed temporal dynamics consistent with reactive microgliosis.
• A significant correlation was found between DCI-derived extra-axonal restricted diffusion and histological microglial density.
• This parameter serves as a potential in-vivo marker for reactive microglia.

Conclusions:

• Extra-axonal restricted diffusion measured by DCI is a valid in-vivo marker of reactive microglia.
• DCI-based microglial mapping could enhance the characterization of neurological and psychiatric diseases.
• This research paves the way for non-invasive MRI assessment of neuroinflammation.