Identification of fibers at risk for degeneration by diffusion tractography in patients at high risk for MS after a clinically isolated syndrome

Purpose: Focal inflammatory/demyelinating lesions are thought to be the source of Wallerian degeneration or other injury to local, transiting fiber tracts in the brain or spinal cord in multiple sclerosis (MS). A methodology is established to isolate connections between focal demyelinating lesions and intersecting fibers to permit explicit analyses of the pathology of secondary fiber injury distant from the focal lesion. Materials and Methods: A strategy is described and feasibility demonstrated in three patients with a clinically isolated syndrome and positive MRI (at high risk for MS). The strategy utilizes streamtube diffusion tractography to identify neuronal fibers that intersect a focal lesion and pass through a region of interest, in this case the corpus callosum, where distal (to focal lesion) interrogation can be accomplished. Results: A sizeable fraction of the normal appearing white matter (NAWM) in the early stages of disease can be defined in the corpus callosum, which is distinctive in that this tissue connects to distant demyelinating lesions. Conclusion: The new class of tissue called fibers-at-risk for degeneration (FAR) can be identified and interrogated by a variety of quantitative MRI methodologies to better understand neuronal degeneration in MS.