Orientation Dependent MR Signal Decay Differentiates between People with MS, Their Asymptomatic Siblings and Unrelated Healthy Controls.
R2* relaxometry of the brain is a quantitative magnetic resonance technique which is influenced by iron and myelin content across different brain regions. Multiple sclerosis (MS) is a common inflammatory, demyelinating disease affecting both white and grey matter regions of the CNS. Using R2*, increased iron deposition has been described in deep gray matter of MS patients. Iron accumulation might promote oxidative stress in the brain, which can lead to cell death and neurodegeneration. However, recent histological work indicates that iron may be reduced within the normal appearing white matter (WM) in MS. In the present study we analyzed the R2* signal across the white matter in 39 patients with MS, 31 asymptomatic age matched siblings of patients and 30 age-matched controls. The measurement of R2* in white matter is affected by the signal's dependency on white matter fibre orientation with respect to the main magnetic field which can be accounted using diffusion tensor imaging. We observed a clear separation of the three study groups in R2*. The values in the MS group were significantly lower compared to the siblings and controls, while the siblings group presented with significantly higher R2* values than both unrelated healthy controls and patients. Furthermore, we found significantly decreased normal-appearing white matter R2* values in patients with more severe disease course. Angle resolved analysis of R2* improves the sensitivity for detecting subtle differences in WM R2* compared to standard histogram based analyses. Our findings suggest that the decreased R2* values in MS are due to diffuse tissue damage and decreased myelin in the normal appearing and diffusely abnormal WM. The increased R2* in unaffected siblings may identify a predisposition to increased iron and the potential for oxidative stress as a risk factor for developing MS.
UBC MRI Research Centre, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Enedino
E
Hernández-Torres
UBC MRI Research Centre, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada; Department of Physics and Astronomy, University of British Columbia, Vancouver, Canada.
Vanessa
V
Wiggermann
Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Simon
S
Hametner
UBC MRI Research Centre, University of British Columbia, Vancouver, Canada; Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, Canada; Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, Canada.
Tobias R
TR
Baumeister
Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada; Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
A Dessa
AD
Sadovnick
Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada.
Yinshan
Y
Zhao
Department of Radiology, University of British Columbia, Vancouver, Canada.
Lindsay
L
Machan
UBC MRI Research Centre, University of British Columbia, Vancouver, Canada; Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada; Department of Radiology, University of British Columbia, Vancouver, Canada.
David K B
DK
Li
Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada; Centre for Brain Health, University of British Columbia, Vancouver, Canada.
Anthony
A
Traboulsee
UBC MRI Research Centre, University of British Columbia, Vancouver, Canada; Department of Pediatrics, University of British Columbia, Vancouver, Canada; Centre for Brain Health, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
Alexander
A
Rauscher
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000503:physiopathology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress; D035781:Siblings; D066127:White Matter / Q000503:physiopathology*
D007501:Iron