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Empirical relationship between TEM-derived myelin volume fraction and MRI-R2 values in aging ex vivo rat corpus
Hwapyeong Cho1, Sohyun Han2, Hyung Joon Cho1
1Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
Abstract:
Ex vivo ratiometric measurements of short- and long-T2 components using the multiple spin echo sequence of MRI are often employed to evaluate alterations in myelin content in the white matter (WM) of the brain. However, the relationship between absolute MRI-T2 values (long-T2 component) and myelin volumetric information in aged ex vivo rodent WM appears to be influenced by factors such as animal species, field strength, and fixation durations/washing. Here, multiple spin echo sequence-based MRI-R2 (the reciprocal of T2) values were measured in the corpus callosum (CC) region in the post-mortem rat brains (n = 9) of different age groups with common fixation techniques without washing at 7 T. Transmission electron microscopy (TEM)-based quantification of myelin volume fraction (MVF) and corresponding Monte-Carlo simulation to estimate relaxation rates (R2,IE) due to diffusion in the presence of inhomogeneous magnetic field perturbation in intra- and extra-cellular (IE) spaces were respectively performed. To determine whether the short-T2 components originating from myelin water were mixed with long-T2 components from IE water or were undetectable, the MVF values obtained from TEM results were respectively compared with MRI-R2 and R2,IE values. A significant correlation (Pearson's correlation coefficient r = 0.8763; p < 0.01) of average MRI-R2 and MVF values was observed. Estimated R2,IE values from Monte-Carlo simulations in IE water signals were also positively correlated (r = 0.8281; p < 0.01) with MVF values. However, the magnitudes of R2,IE values were much smaller than those observed for MRI-R2 values, indicating that changes in R2 related MVF are likely dominated by myelin water components. Such comparisons between independent parameters from MRI, TEM, and simulations support the suggestion that myelin water signals were indistinguishably mixed to exhibit mono-exponential T2 relaxation, and multiple spin echo sequence-based MRI-R2 values in aging ex vivo rat CC without prolonged washing still reflect the volumetric information of myelin, likely due to enhanced water exchange across the myelin.
Insights
Magnetic Resonance Imaging R2 values in aging rat brains correlate with myelin volume fraction, indicating MRI can assess myelin content without extensive sample preparation. This finding is crucial for understanding white matter changes.
Area of Science:
- Neuroimaging
- Biophysics
- Neuroscience
Background:
- Magnetic Resonance Imaging (MRI) multiple spin echo sequences measure T2 relaxation components to assess white matter (WM) myelin content.
- Previous studies show MRI-T2 values in aged ex vivo rodent WM are influenced by species, field strength, and fixation/washing protocols.
- The precise relationship between MRI relaxation rates and myelin volumetric information in aged ex vivo rodent WM requires further clarification.
Purpose of the Study:
- To investigate the correlation between MRI-R2 values and myelin volume fraction (MVF) in aging ex vivo rat corpus callosum (CC) without washing.
- To determine if short-T2 components from myelin water are mixed with long-T2 components from intra- and extra-cellular (IE) water.
- To validate MRI-R2 as a reliable measure of myelin content in aging rodent brains.
Main Methods:
- Ex vivo MRI-R2 values were measured at 7 Tesla in post-mortem rat brains (n=9) from different age groups using a multiple spin echo sequence.
- Transmission Electron Microscopy (TEM) quantified myelin volume fraction (MVF).
- Monte-Carlo simulations estimated relaxation rates (R2,IE) in intra- and extra-cellular spaces.
Main Results:
- A significant positive correlation was observed between average MRI-R2 values and TEM-derived MVF (r=0.8763, p<0.01).
- Estimated R2,IE values also positively correlated with MVF (r=0.8281, p<0.01), but were significantly smaller than MRI-R2 values.
- The findings suggest that MRI-R2 changes are primarily driven by myelin water components, not IE water.
Conclusions:
- Myelin water signals appear indistinguishably mixed, exhibiting mono-exponential T2 relaxation in aging ex vivo rat CC.
- Multiple spin echo sequence-based MRI-R2 values, even without prolonged washing, reflect myelin volumetric information.
- Enhanced water exchange across myelin likely contributes to the observed MRI-R2 and MVF correlation.
