Correlations of quantitative MRI metrics with myelin basic protein (MBP) staining in a murine model of demyelination

Abstract

Myelin imaging in the central nervous system is essential for monitoring pathologies involving white matter alterations. Various quantitative MRI protocols relying on the modeling of the interactions of water protons with myelinated tissues have shown sensitivities in case of myelin disruption. Some extracted model parameters are more sensitive to demyelination, such as the bound pool fraction (f) in quantitative magnetization transfer imaging (qMTI), the radial diffusivity in diffusion tensor imaging (DTI), and the myelin water fraction (MWF) in myelin water imaging (MWI). A 3D ultrashort echo time (UTE) sequence within an appropriate water suppression condition (Diff‐UTE) is also considered for the direct visualization of the myelin semi‐solid matrix (Diff‐UTE normalized signal; rSPF). In this paper, we aimed at assessing the sensitivities and correlations of the parameters mentioned above to an immuno‐histological study of the myelin basic protein (MBP) in a murine model of demyelination at 7 T. We demonstrated a high sensitivity of the MRI metrics to demyelination, and strong Spearman correlations in the corpus callosum between histology, macromolecular proton fraction (ρ>0.87) and Diff‐UTE signal (ρ>0.76), but moderate ones with radial diffusivity and MWF (|ρ|<0.70).

Determination of optimal parameters for 3D single‐point macromolecular proton fraction mapping at 7T in healthy and demyelinated mouse brain

“…MPF values measured in WM and GM regions in this study are in average similar to those reported by Ou et al 17 (recalculated from the pool size ratio), Thiessen et al, 13 and by our group 14 in paraformaldehyde‐fixed mouse brains. Values were somewhat lower than those estimated by Khodanovich et al 23 in in vivo mice at 11.7T, although precise constrained parameters were not provided.…”

“…32,33 Fields of view (FOV) were tilted so that their respective edge was parallel to the corpus callosum along the genusplenium line determined on a 2D T 2 -weighted sagittal scan, thus mitigating potential partial volume effects. 14 All native images were denoised using BM4D 34 (exemplified in Supporting Information Figure S1, which is available online) and rigidly registered onto the 10-degrees volume of the T 1 mapping protocol using ANTs. 35 Brain extraction was manually performed using ITK-SNAP.…”

“…Fields of view (FOV) were tilted so that their respective edge was parallel to the corpus callosum along the genu‐splenium line determined on a 2D T 2 ‐weighted sagittal scan, thus mitigating potential partial volume effects 14 …”

“…[3][4][5][6][7][8] Sampling the Z-spectrum to derive quantitative MT parameters is time consuming because different MT-weighted (MTw) images must be acquired with a set of MT saturation pulses differing in power and off-resonance frequency. Thus, few studies reported on comprehensive qMT protocols at a whole-brain scale in living animals, 9,10 2D 11,12 and ex vivo [13][14][15][16][17] explorations being preferred.…”

Quantitative susceptibility mapping and R1 measurement: Determination of the myelin volume fraction in the aging ex vivo rat corpus callosum

“…Postmortem formalin‐fixed brains showed significant changes in the MT ratio (MTR), which weakened the association between MT effects and myelin content 11 . A postmortem MWI study also showed that the T 2 distribution can be altered, probably because of myelin sheath loosening, cell shrinkage, and changes in various water compartments during the fixation process 12,13 …”