Strategy for Detecting Neuronal Fibers at Risk for Neurodegeneration In Earliest MS by Streamtube Tractography at 3T

Abstract

Background: While demyelination is central to the onset of MS, focal inflammatory MS lesions are also characterized by axonal injury, including transections[1]. As a result, the study of axonal injury has become an important new area of MS research, and axonal injury is now considered an important contributor to irreversible injury, disability and possibly conversion to progressive stages of disease. In advanced stages of MS, there is direct evidence for significant neuronal loss for example in corpus callosum [2]. In early MS, there is circumstantial evidence for neuronal tract injury due to focal, inflammatory demyelinating lesions associated with a clinically isolated syndrome (CIS) based on neuronal tract (Wallerian) degeneration patterns in corticospinal tract [3] and across the corpus callosum (transcallosal bands) [4]. The presence of such axonal injury is supported by an informative case study where confocal microscopy revealed empty myelin cylinders in spinal cord of an MS patient with a distant subacute brainstem lesion [5]. Purpose: We report an MRI strategy to detect “at-risk ” neuronal fibers in the corpus callosum related to distant focal demyelinating lesions. This strategy is necessary since a priori assumptions about the anatomical location of lesions relative to fiber tracts is often misleading. Methods: We conducted a prospective longitudinal study including 18 CIS patients with an MRI (at least 2 characteristic T2-lesions) placing them at high risk for the development of MS [6]. MRI acquisition was at 3T and included 3mm thick non-gapped proton density/T2 series and sagittal fast spin echo (FSE) T2-weighted imaging with 3mm non-gapped slices. A diffusion tensor imaging sequence is run in the axial plane with sets of diffusion tensor images acquired by echo-plana