title: Susceptibility-weighted imaging in the experimental autoimmune encephalomyelitis model of multiple sclerosis indicates elevated deoxyhemoglobin, iron deposition and demyelination.
abstract: 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 deoxyhemoglobin to the signals seen in SWI has not been well characterized in MS.
  
  
  OBJECTIVE
  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 deoxyhemoglobin 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 deoxyhemoglobin 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 deoxyhemoglobin in the blood, and so may indicate areas of hypoxia. A smaller number of SWI lesions coincided with parenchymal iron, demyelination, and/or inflammation.
authors.affiliation: University of Calgary, AB, Canada.
authors.forename: Nabeela
authors.initials: N
authors.lastname: Nathoo
authors.forename: Smriti
authors.initials: S
authors.lastname: Agrawal
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Sarah
authors.initials: S
authors.lastname: Haylock-Jacobs
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.forename: Tad
authors.initials: T
authors.lastname: Foniok
authors.forename: Samuel
authors.initials: S
authors.lastname: Barnes
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D005260:Female; D005620:Freund's Adjuvant; D006454:Hemoglobins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism*; D037342:Pertussis Toxin; D011237:Predictive Value of Tests; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology*; D066127:White Matter / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D005620:Freund's Adjuvant; C100003:deoxyhemoglobin; D007501:Iron; D037342:Pertussis Toxin