Various MRI techniques, including myelin water imaging, T1w/T2w ratio mapping and diffusion-based imaging can be used to characterize tissue microstructure. However, surprisingly few studies have examined the degree to which these MRI measures are related within and between various brain regions. Therefore, whole-brain MRI scans were acquired from 31 neurologically-healthy participants to empirically measure and compare myelin water fraction (MWF), T1w/T2w ratio, fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) in 25 bilateral (10 grey matter; 15 white matter) regions-of-interest (ROIs). Except for RD vs. T1w/T2w, MD vs. T1w/T2w, moderately significant to highly significant correlations (p < 0.001) were found between each of the other measures across all 25 brain structures [T1w/T2w vs. MWF (Pearson r = 0.33, Spearman ρ = 0.31), FA vs. MWF (r = 0.73, ρ = 0.75), FA vs. T1w/T2w (r = 0.25, ρ = 0.22), MD vs. AD (r = 0.57, ρ = 0.58), MD vs. RD (r = 0.64, ρ = 0.61), AD vs. MWF (r = 0.43, ρ = 0.36), RD vs. MWF (r = −0.49, ρ = −0.62), MD vs. MWF (r = −0.22, ρ = −0.29), RD vs. FA (r = −0.62, ρ = −0.75) and MD vs. FA (r = −0.22, ρ = −0.18)]. However, while all six MRI measures were correlated with each other across all structures, there were large intra-ROI and inter-ROI differences (i.e., with no one measure consistently producing the highest or lowest values). This suggests that each quantitative MRI measure provides unique, and potentially complimentary, information about underlying brain tissues – with each metric offering unique sensitivity/specificity tradeoffs to different microstructural properties (e.g., myelin content, tissue density, etc.).

PurposePostmortem MRI can be used to reveal important pathologies and establish radiology–pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this study was to investigate time-dependent effects of formalin fixation on MRI relaxometry (T1 and T2), diffusion tensor imaging (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens.MethodsTwo whole, neurologically-healthy human brains were immersed in 10% formalin solution and scanned at 13 time points between 0 and 1,032 h. Whole-brain maps of longitudinal (T1) and transverse (T2) relaxation times, FA, MD, and MWF were generated at each time point to illustrate spatiotemporal changes, and region-of-interest analyses were then performed in eight brain structures to quantify temporal changes with progressive fixation.ResultsAlthough neither of the diffusion measures (FA nor MD) showed significant changes as a function of formalin fixation time, both T1 and T2-relaxation times significantly decreased, and MWF estimates significantly increased with progressive fixation until (and likely beyond) our final measurements were taken at 1,032 h.ConclusionThese results suggest that T1-relaxation, T2-relaxation and MWF estimates must be performed quite early in the fixation process to avoid formalin-induced changes compared to in vivo values; and furthermore, that different ex vivo scans within an experiment must be acquired at consistent (albeit still early) fixation intervals to avoid fixative-related differences between samples. Conversely, ex vivo diffusion measures (FA and MD) appear to depend more on other factors (e.g., pulse sequence optimization, sample temperature, etc.).

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

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