Sensitivity to myelin using model-free analysis of the water resonance line-shape in postmortem mouse brain

Purpose Dysmyelinating diseases are characterized by abnormal myelin formation and function. Such microstructural abnormalities in myelin have been demonstrated to produce measurable effects on the MR signal. This work examines these effects on measurements of voxel-wise, high-resolution water spectra acquired using a 3D echo-planar spectroscopic imaging (EPSI) pulse sequence from both postmortem fixed control mouse brains and a dysmyelination mouse brain model. Methods Perfusion fixed, resected control (n= 5) and shiverer (n= 4) mouse brains were imaged using 3D-EPSI with 100 mu m isotropic resolution. The free induction decay (FID) was sampled every 2.74 ms over 192 echoes, for a total sampling duration of 526.08 ms. Voxel-wise FIDs were Fourier transformed to produce water spectra with 1.9 Hz resolution. Spectral asymmetry was computed and compared between the two tissue types. Results The water resonance is more asymmetrically broadened in the white matter of control mouse brain compared with dysmyelinated white matter. In control brain, this is modulated by and consistent with previously reported orientationally dependent effects of white matter relative to B-0. Similar sensitivity to orientation is observed in dysmyelinated white matter as well; however, the magnitude of the resonance asymmetry is much lower across all directions. Conclusion Results demonstrate that components of the spectra are specifically differentially affected by myelin concentration. This suggests that water proton spectra may be sensitive to the presence of myelin, and as such, could serve as a MRI-based biomarker of dysmyelinating disease, free of mathematical models.