Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

Area of Science:

• Neuroimmunology
• Neuroinflammation
• Magnetic Resonance Imaging

Background:

• Microglia, the resident immune cells of the central nervous system (CNS), play dual roles in health and disease.
• In multiple sclerosis (MS), myeloid cells like microglia and macrophages contribute to white matter lesion development and progression.
• Chronic active MS lesions feature activated myeloid cells with iron accumulation, driving persistent tissue damage.

Purpose of the Study:

• To review the role of iron-positive myeloid cells in chronic active lesions in MS.
• To highlight quantitative susceptibility mapping (QSM) as a tool for visualizing and quantifying these cells.
• To discuss the potential of QSM as an in vivo biomarker for chronic inflammation in MS.

Main Methods:

• Review of existing literature on microglia, macrophages, and MS pathology.
• Discussion of iron accumulation in myeloid cells within chronic active MS lesions.
• Introduction of quantitative susceptibility mapping (QSM) for in vivo imaging of iron.

Main Results:

• Myeloid cells in chronic active MS lesions are characterized by iron accumulation and pro-inflammatory polarization.
• These iron-positive myeloid cells are activated over extended periods (years), contributing to ongoing tissue damage.
• Quantitative susceptibility mapping (QSM) can effectively visualize and quantify iron-positive myeloid cells in MS lesions.

Conclusions:

• Iron-positive myeloid cells in chronic active MS lesions represent a significant driver of chronic inflammation and tissue damage.
• Quantitative susceptibility mapping (QSM) shows promise as a non-invasive in vivo biomarker for chronic inflammatory activity in MS.
• Targeting iron accumulation and chronic inflammation may be a therapeutic strategy to impact MS severity and progression.