Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients

Axonal degeneration of white matter fibers is a key consequence of neuronal or axonal injury. It is characterized by a series of time-related events with initial axonal membrane collapse followed by myelin degradation being its major hallmarks. Standard imaging cannot differentiate these phenomena, which would be useful for clinical investigations of degeneration, regeneration and plasticity. Animal models suggest that diffusion tensor magnetic resonance imaging (DTI) is capable of making such distinction. The applicability of this technique in humans would permit inferences on white matter microanatomy using a non-invasive technique. The surgical bisection of the anterior 2/3 of the corpus callosum for the palliative treatment of certain types of epilepsy serves as a unique opportunity to assess this method in humans. DTI was performed on three epilepsy patients before corpus callosotomy and at two time points (1 week and 2–4 months) after surgery. Tractography was used to define voxels of interest for analysis of mean diffusivity, fractional anisotropy and eigenvalues. Diffusion anisotropy was reduced in a spatially dependent manner in the genu and body of the corpus callosum at 1 week and remained low 2–4 months after the surgery. Decreased anisotropy at 1 week was due to a reduction in parallel diffusivity (consistent with axonal fragmentation), whereas at 2–4 months, it was due to an increase in perpendicular diffusivity (consistent with myelin degradation). DTI is capable of non-invasively detecting, staging and following the microstructural degradation of white matter following axonal injury.