Multiple Sclerosis: Validation of MR Imaging for Quantification and Detection of Iron

Abstract

All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

“…The interpretation of our in vivo MRI data and postmortem findings (Figure 7) is, therefore, not in conflict with the pathological finding of iron accumulation within a subset of macrophages/activated microglia at the edge of chronic phase rim lesions (13,14,19,20,25,39), even if other relevant factors, such as oxidative stress and disruption of the microstructural organization of the tissue (39-42), may also affect the phase signal in active lesions. The role of iron in such lesions is complex, as iron -cells, red arrows).…”

“…However, against this hypothesis, a few short-term longitudinal MRI studies (~1-2 years) failed to demonstrate that chronic rim lesions expand over time into the surrounding normal tissue (16,18), although MRI studies with longer follow-up are still needed. Furthermore, existing radiological-pathological correlation studies have not resulted in a clear consensus on the extent to which the magnetic susceptibility-related MRI signal change in the lesion rim is caused only by iron deposition (iron-laden macrophages, ferritin, and/ or hemosiderin deposits) (13,14,19,20) or by other MS-relevant comprehensive biological model of lesion development, are necessary to elucidate the rim's pathophysiological significance and potential relationship with mechanisms of lesion repair. In a crosssectional MRI study (16), coupling susceptibility-based imaging and dynamic contrast-enhanced (DCE) imaging at 7 tesla (7T), we showed that the rim is best appreciated on phase (rather than T2*) images, that it may reflect the inflammatory edge (macrophages/microglia, their byproducts, and oxidative stress) of the newly forming lesion, and that it colocalizes with blood-brain-barrier opening in centripetally enhancing lesions (16,21,22).…”

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

“…5,[7][8][9][10][11] Among the MR imaging measures used, only the gradient-echo transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) have been validated against postmortem iron assessment, both in non-MS 12,13 and in MS populations. 14,15 Three MS studies assessed different aspects of cognition along with R2*. 5,10,11 In Khalil et al, 5 R2* in the basal ganglia (but not in the thalamus) was related to processing speed in patients with clinically isolated syndrome and those with MS.…”

Quantitative susceptibility mapping in patients with systemic lupus erythematosus: detection of abnormalities in normal-appearing basal ganglia

“…The positive correlation between the QSM values in the putamen and the disease duration in the NPSLE patients also supports the assumption that the accumulation of iron in the putamen occurs as a by-product of pathophysiologic processes of this disease. In previous studies with multiple sclerosis, the investigators also suggest that the susceptibility/iron differences may be caused not only by demyelination but also inflammation [9][10][11][12][13][14]. Another possible explanation is that disruption of the axonal transportation of iron due to SLE-related brain damage results in the deposition of iron in the putamen.…”

“…However, SLE fundamentally involves inflammation, which is very difficult to detect using these radiographic techniques [8]. There have been substantial developments in iron-sensitive MRI to detect inflammation, such as in another neuroinflammatory disease, multiple sclerosis, that involves microglia/macrophages loaded with iron [9][10][11][12][13][14]. Accordingly, we propose to apply an ironquantification MRI technique, quantitative susceptibility mapping (QSM), to SLE brains to investigate possible ironassociated changes in NPSLE brains.…”