Iron in the brain by a new MRI technique (QSM)

[frodo]

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

https://www.frontiersin.org/articles/10 ... 00255/full

This article debunks a lot of myths. Some extracts:

... A striking feature of chronic active MS lesions is that iron is highly enriched in activated microglia and macrophages at the lesion edge (27), which has implications for their function and in vivo detection in MS patients,

... Furthermore, high iron induces glutamate release by neurons (61, 62), which potentially leads to excitotixicity in neurons and oligodendrocytes.

... The source of iron in MS lesions is unknown, but it is tempting to speculate that the destruction of iron-rich myelin and oligodendrocytes during lesion formation leads to iron release into the extracellular space and eventual uptake by myeloid cells.

... Acutely demyelinating lesions can be visualized through gadolinium that accumulates within lesions with temporary breakdown of the BBB. However, gadolinium enhancement offers only a small window into early inflammatory activity, as the BBB closes within weeks of lesion formation. Gadolinium enhancement in MS lesions is preceded and outlasted by infiltration with immune cells. This has been demonstrated in MS patients with positron emission tomography (PET) imaging studies using radioactive ligands for the 18-kDa translocator protein, and with MRI of ultra-small iron-oxide particles that were injected peripherally and detected in activated monocytes/macrophages infiltrating the lesions.

... These imaging results are consistent with histological studies indicating that significant inflammatory activity occurs behind a closed BBB

... The therapeutic goal of managing MS patients is to completely suppress CNS inflammation. Thus the inability to detect chronic inflammation in MS with conventional MRI techniques is a significant, unmet need in clinical practice.

... QSM permits visualization of the sizes and shapes of iron sources, delivers precise estimates of iron concentrations, and distinguishes between susceptibility sources such as iron and calcification

... their data suggest that the QSM contrast between lesions and the surrounding NAWM may be driven by pathological changes known to be present in NAWM.

... lesions acquired iron as they transitioned from an acute to a chronic active state. The elevated susceptibility was stable for approximately 4 years and then decayed to levels similar to that of NAWM

... suggest that heterogenous QSM patterns were typically associated with the presence of heme within enlarged blood vessels in MS lesions.

... although susceptibility weighted imaging (SWI) cannot distinguish between iron accumulation and myelin loss, increased susceptibility at the lesion rim likely represents chronically activated, iron-positive microglia and macrophages.

... we are testing the ability of current MS treatments to remove iron from existing white matter lesions in MS patients. Of particular interest are MS medications that penetrate the BBB and act directly on microglia, such as dimethyl fumarate (Tecfidera™), fingolimod (Gilenya™), and Laquinimod

... the emerging picture suggests that iron-positive microglia and macrophages in chronic active MS lesions constitute a distinct, previously unappreciated inflammatory compartment that may be a significant contributor to tissue damage, disease severity, and/or progression.