Research: Iron depositing in EAE

Nathoo N  et al. Susceptibility-weighted imaging in the experimental autoimmune encephalomyelitis model of multiple sclerosis indicates elevated deoxyhemoglobin, iron deposition and demyelination Mult Scler 1352458512460602, doi:10.1177/1352458512460602 
 
Background: Susceptibility-weighted imaging (SWI) is an iron-sensitive magnetic resonance imaging (MRI) method that has shown iron-related lesions in multiple sclerosis (MS) patients. The contribution of deoxyhaemoglobin to the signals seen in SWI has not been well characterized in MS.

Objectives: To determine if SWI lesions (seen as focal hypointensities) exist in the experimental autoimmune encephalomyelitis (EAE) animal model of MS, and to determine whether the lesions relate to iron deposits, inflammation, demyelination, and/or deoxyhaemoglobin in the vasculature.

Methods: We performed SWI on the lumbar spinal cord and cerebellum of EAE and control mice (both complete Freund’s adjuvant/pertussis toxin (CFA/PTX)-immunized and naive). We also performed SWI on mice before and after perfusion (to remove blood from vessels). SWI lesions were counted and their locations were compared to histology for iron, myelin and inflammation.

Results: SWI lesions were found to exist in the EAE model. Many lesions seen by SWI were not present after perfusion, especially at the grey/white matter boundary of the lumbar spinal cord and in the cerebellum, indicating that these lesion signals were associated with deoxyhaemoglobin present in the lumen of vessels. We also observed SWI lesions in the white matter of the lumbar spinal cord that corresponded to iron deposition, inflammation and demyelination. In the cerebellum, SWI lesions were present in white matter tracts, where we found histological evidence of inflammatory perivascular cuffs.

Conclusions: SWI lesions exist in EAE mice. Many lesions seen in SWI were a result of deoxyhaemoglobin in the blood, and so may indicate areas of hypoxia. A smaller number of SWI lesions coincided with parenchymal iron, demyelination, and/or inflammation. 


Susceptibility weighted imaging (SWI), originally called BOLD venographic imaging, uses a type of contrast in magnetic resonance imaging (MRI) different from traditional spin density, T1, or T2 imaging. SWI uses a fully flow compensated, long echo, gradient echo (GRE) scan to acquire images. This method exploits the susceptibility differences between tissues and uses the phase image to detect these differences. The magnitude and phase data are combined to produce an enhanced contrast magnitude image which is exquisitely sensitive to venous blood, hemorrhage and iron storage. The imaging of venous blood with SWI is a blood-oxygen-level dependent (BOLD) technique which is why it was (and is sometimes still) referred to as BOLD venography. There is apparent iron deposition in EAE  and hypoxia in animals which have not got CCSVI. maybe as occurs in MS

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