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Differences in iron and manganese concentration may confound the measurement of myelin from R 1 and R 2 relaxation rates in studies of dysmyelination

DOI: 10.1002/nbm.3549 DOI Help

Authors: Kimberly L. Desmond (Psychology, Neuroscience and Behaviour, McMaster University; Sunnybrook Research Institute) , Alia Al-ebraheem (McMaster university) , Rafal Janik (Sunnybrook Research Institute; University of Toronto) , Wendy Oakden (Sunnybrook Research Institute; University of Toronto) , Jacek M. Kwiecien (Pathology & Molecular Medicine, McMaster University; Department of Clinical Pathomorphology, Lublin Medical University) , Wojciech Dabrowski (Anaesthesiology and Intensive Therapy, Lublin Medical University) , Radoslaw Rola (Neurosurgery & Pediatric Neurosurgery, Lublin Medical University) , Tina Geraki (Diamond Light Source) , Michael Farquharson (McMaster university) , Greg J. Stanisz (Sunnybrook Research Institute; University of Toronto; Neurosurgery & Pediatric Neurosurgery, Lublin Medical University) , Nicholas A. Bock (Psychology, Neuroscience and Behaviour, McMaster University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nmr In Biomedicine

State: Published (Approved)
Published: May 2016
Diamond Proposal Number(s): 9704

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.

Journal Keywords: iron;manganese;myelin;Shaker;les;relaxometry;micro-synchrotron radiation X-ray fluorescence (μSRSRF);cerebellum

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I18-Microfocus Spectroscopy

Other Facilities: Anka