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Background: Changes in myelin integrity are associated with the pathophysiology of many neurological diseases, including multiple sclerosis. However, noninvasive measurement of myelin injury and repair remains challenging. Advanced MRI techniques including diffusion tensor imaging (DTI), neurite orientation dispersion and density index (NODDI), and texture analysis have shown promise in quantifying subtle abnormalities in white matter structure., Purpose: To determine whether and how these advanced imaging methods help understand remyelination changes after demyelination using a mouse model., Study Type: Prospective, longitudinal., Animal Model: Demyelination was induced in the thoracic spinal cord of 21 mice using the chemical toxin lysolecithin., Field Strength/sequences: 9.4T ASSESSMENT: Imaging was done at day 7 (demyelination) and days 14 to 35 (ongoing remyelination) postsurgery, followed by histology. Image analysis focused on both lesions and peri-lesional areas where remyelination began. In histology, we quantified the complexity of tissue alignment using angular entropy, in addition to staining area., Statistical Analysis: Two-way analysis of variance was performed for assessing differences between tissue types and across timepoints, followed by post-hoc analysis to correct for multiple comparisons (P < 0.05)., Results: All diffusion and texture parameters were worse in lesions than the control tissue (P < 0.05) except orientation dispersion index (ODI) and neurite density index (NDI) over late remyelination. Longitudinally, ODI decreased and NDI increased persistently in both lesions and peri-lesion regions (P < 0.05). Fractional anisotropy showed a mild decrease at day 35 after increase, when lesion texture heterogeneity showed a trend to decrease (P > 0.05). Both lesion size and angular entropy decreased over time, and no change in any measure in the control tissue., Data Conclusion: Diffusion and MRI texture metrics may provide compensatory information on myelin repair and ODI and NDI could be sensitive measures of evolving remyelination, deserving further validation., Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1750-1759., (© 2018 International Society for Magnetic Resonance in Medicine.)

For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents. Interestingly, following its injection into white matter, LPC was cleared within 24 hr but by five days there was an elevation of endogenous LPC that was not associated with damage. This elevation of LPC in the absence of injury raises the possibility that the brain has mechanisms to buffer LPC. In support, LPC injury in culture was significantly ameliorated by albumin buffering. These results shed light on the mechanisms of LPC injury and homeostasis., (© 2017 Wiley Periodicals, Inc.)