title: Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination.
abstract: A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1  = 1/T1 and R2  = 1/T2 , at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.55 ± 0.08 s (-1) and R2 was found to be 15 ± 1 s(-1) , revealing significantly lower R1 and R2 in les white matter relative to wild-type (wt: R1  = 0.69 ± 0.05 s(-1) and R2  = 18 ± 1 s(-1) ). These deviated from the expected ΔR1 and ΔR2 values, given a complete lack of myelin in the les white matter, derived from the literature using values of myelin relaxivity, and we suspect that metals could play a significant role. The absolute concentrations of the paramagnetic transition metals iron (Fe) and manganese (Mn) were measured by a micro-synchrotron radiation X-ray fluorescence (μSRXRF) technique, with significantly greater Fe and Mn in les white matter than in wt (in units of μg [metal]/g [wet weight tissue]: les: Fe concentration,19 ± 1; Mn concentration, 0.71 ± 0.04; wt: Fe concentration,10 ± 1; Mn concentration, 0.47 ± 0.04). These changes in Fe and Mn could explain the deviations in R1 and R2 from the expected values in white matter. Although it was found that the influence of myelin still dominates R1 and R2 in wt rats, there were non-negligible changes in the contribution of the metals to relaxation. Although there are already problems with the estimation of myelin from R1 and R2 changes in disease models with pathology that also affects the relaxation rate constants, this study points to a specific pitfall in the estimation of changes in myelin in diseases or models with disrupted concentrations of paramagnetic transition metals. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.|Imaging Research, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Desmond
authors.affiliation: School of Interdisciplinary Science, Medical Radiation Sciences program, McMaster University, Hamilton, ON, Canada.
authors.forename: Alia
authors.initials: A
authors.lastname: Al-Ebraheem
authors.affiliation: Imaging Research, Sunnybrook Research Institute, Toronto, ON, Canada.|Medical Biophysics, University of Toronto, ON, Canada.
authors.forename: Rafal
authors.initials: R
authors.lastname: Janik
authors.affiliation: Imaging Research, Sunnybrook Research Institute, Toronto, ON, Canada.|Medical Biophysics, University of Toronto, ON, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Oakden
authors.affiliation: Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.|Department of Clinical Pathomorphology, Lublin Medical University, Lublin, Poland.
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Kwiecien
authors.affiliation: Anaesthesiology and Intensive Therapy, Lublin Medical University, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dabrowski
authors.affiliation: Neurosurgery & Pediatric Neurosurgery, Lublin Medical University, Lublin, Poland.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Rola
authors.affiliation: Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.
authors.forename: Kalotina
authors.initials: K
authors.lastname: Geraki
authors.affiliation: School of Interdisciplinary Science, Medical Radiation Sciences program, McMaster University, Hamilton, ON, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Farquharson
authors.affiliation: Imaging Research, Sunnybrook Research Institute, Toronto, ON, Canada.|Medical Biophysics, University of Toronto, ON, Canada.|Neurosurgery & Pediatric Neurosurgery, Lublin Medical University, Lublin, Poland.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stanisz
authors.affiliation: Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bock
mesh_terms: D000818:Animals; D016477:Artifacts; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008345:Manganese / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology
chemical_list: D008345:Manganese; D007501:Iron
keywords: Shaker; cerebellum; iron; les; manganese; micro-synchrotron radiation X-ray fluorescence (μSRSRF); myelin; relaxometry