Differences in iron and manganese concentration may confound the measurement of myelin fromR₁andR₂relaxation 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.

Whole-brain ex-vivo quantitative MRI of the cuprizone mouse model

“…It would be useful to better understand the contribution of myelin and inflammation to the different MR parameters, similarly to how Desmond et al (2016) developed a model of the contribution of myelin and metals to T1&T2. In our opinion, due to the strength of the correlations the single time point presented here is insufficient to build such a model.…”

Relationship between aging and T1 relaxation time in deep gray matter: A voxel‐based analysis

“…Aging changes in GM have predominantly been investigated based on ‐weighted signal changes and quantitative susceptibility mapping (QSM) to detect iron deposition . However, the deposition of iron and manganese also alters the T 1 relaxation time of the tissue . As the concentration of iron is higher in deep GM than WM, the correlation of age and T 1 values in deep GM is expected to differ from that for WM.…”

“…12,13 However, the deposition of iron and manganese also alters the T 1 relaxation time of the tissue. 14,15 As the concentration of iron is higher in deep GM than WM, the correlation of age and T 1 values in deep GM is expected to differ from that for WM.…”

Early regional cuprizone‐induced demyelination in a rat model revealed with MRI

“…Two identical high‐resolution T 1 ‐weighted images were acquired using a three‐dimensional magnetization‐prepared rapid acquisition gradient echo (MP‐RAGE) sequence with TE = 2.3 ms, TR = 5.9 ms, inversion time = 1.3 s, four segments, one average, flip angle (FA) of 12°, 192 × 192 × 90 matrix size for an isotropic resolution of 167 μm, with a scan time of 35 min. These acquisition parameters were optimized for myelin contrast at 7 T, based on previous work in humans at 3 T and in dysmyelinated rats at 7 T . The images were acquired separately, rather than as an averaged acquisition, to allow for any motion to be corrected between scans.…”

“…High‐resolution, three‐dimensional myelin contrast ratio (MCR) images of the whole brain were acquired every 2 weeks, using a T 1 ‐weighted sequence optimized for myelin contrast, combined with a proton density (PD)‐weighted sequence that corrected for B 1 receive inhomogeneity. This technique was originally developed for the imaging of myelin in the human brain, and has also been used successfully in a rat model of dysmyelination . Luxol fast blue (LFB) staining was used to assess myelination at each time point.…”