| Summary: | The behavior of MR phase and frequency in demyelination and damage in central nervous tissue white matter arises not only from traditionally associated bulk susceptibility changes, but also from changes to its tissue microstructure. A recently proposed generalized Lorentzian model of microstructure-related magnetic susceptibility effects predicts an increase in MR frequency due to damage in myelin in MS lesions. The same model also predicts reduction in MR frequency due to axonal degeneration. Here, we investigate the effect of both myelin and axonal damage through transection of white matter fibers in the dorsal column of rat cervical spinal cord. This injury generates secondary damage consisting of neurodegeneration along nerve tracts bilateral to the transection site, producing cases of Wallerian and retrograde degeneration free of excessive hemorrhage and inflammation. High-resolution frequency maps of degenerating tracts were correlated with histopathology for axons, myelin, degenerated myelin, and macrophages. Damage to myelin sheaths is prominent in Wallerian degeneration, where we observe strong correlations with increasing frequency up to 8 weeks post-injury. Retrograde degeneration, which consists predominantly of axonal damage, produces decreased frequency shift over time. The MR frequency shifts are sensitive to the effects of macrophage in filtration and debris clearance, which vary with white matter fiber density and affect rates of degeneration. We demonstrate how MR frequency can successfully characterize injury in rat spinal cord white matter in a manner consistent with predictions outlined by the Generalized Lorentzian Approximation Model, and conclude that these results suggest potential applications of MR frequency to supplement or replace current clinical techniques, such as myelin water and diffusion weighted imaging, as a non-invasive and quantitative method of assessing white matter damage in CNS. === Science, Faculty of === Physics and Astronomy, Department of === Graduate
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