Iron related changes in MS lesions and their validity to characterize MS lesion types and dynamics with Ultra‐high field magnetic resonance imaging

Abstract

Iron accumulates with age in the normal human brain. This process is altered at several levels in the brain of multiple sclerosis (MS) patients. Since iron is mainly stored in oligodendrocytes and myelin in the normal brain, its liberation in demyelinating lesions may amplify tissue damage in demyelinating lesions and its uptake in macrophages and microglia may help to more precisely define activity stages of the lesions. In addition, glia cells change their iron import, export and storage properties in MS lesions, which is reflected by alterations in the expression of iron transport molecules. Changes of iron distribution in the brain can be reliably detected by MRI, particularly upon application of Ultra-high magnetic field (7 Tesla). Iron-sensitive MRI allows to more accurately distinguish the lesions in MS from those in other inflammatory brain diseases, to visualize a subset of slowly expanding lesions in the progressive stage of MS and to increase the sensitivity for lesion detection in the gray matter, such as the cerebral cortex or deep gray matter nuclei.

Multi‐spin echo T2 relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging

“…52 This should be taken into consideration when interpreting MWF results, especially in contexts such as aging or multiple sclerosis lesions, where changes in iron content are known to occur independently of myelin. [53][54][55] However, iron in WM is found mainly within oligodendrocytes, co-localized with myelin, 56 and intra-and inter-subject MWF variations are still believed to be driven primarily by myelin content.…”

The origin and development of subcortical U-fibers in gyrencephalic ferrets

“…2c). Another study reported that iron was accumulated at the cortico-subcortical junction in the human brain [30]. We therefore performed Turnbull blue iron staining using coronal sections of the adult ferret brain and found an accumulation of iron in U-fiber regions ( Fig.…”

“…2f). Because iron is mainly stored in ferritin in myelin [30], it seems likely that the accumulation of iron in the U-fiber regions results from myelin accumulation in the U-fiber regions. These results suggest that iron accumulation is another feature of the U-fiber regions.…”

Gliosis and Neurodegenerative Diseases: The Role of PET and MR Imaging

“…Regarding the use of MRI for microgliosis identification, less studies have tried to directly characterize microglial activation in specific brain regions. Changes of iron deposition, quantified using quantitative susceptibility mapping in MR, have been correlated with activated microglia/macrophages at edges of some chronic demyelinated lesions in patients suffering from multiple sclerosis (Dal-Bianco et al, 2017;Gillen et al, 2018;Hametner et al, 2018). Advanced diffusion models, based on neurite orientation dispersion and density imaging (NODDI) in MR, have been proved to be sensitive to microglial density and to the cellular changes associated with microglial activation in a preclinical setting (Yi et al, 2019).…”