Using Diffusion Tensor Imaging and Immunofluorescent Assay to Evaluate the Pathology of Multiple Sclerosis

Purpose: To determine the ability of the principal diffusion tensor imaging (DTI) indices to predict the underlying histopathology evaluated with immunofluorescent assay (IFA). Materials and Methods: Conventional T2 and 3D multi-shot-diffusion weighted echoplanar imaging (3D ms-DWEPI) was performed on a fixed, ex vivo human cervical spinal cord (CSC) from a patient with a history of multiple sclerosis (MS). In all, 170 regions of interest (ROIs) were selected within the white matter and categorized as a high Intensity lesion (HIL), low intensity lesion (LIL), and normal-appearing white matter (NAWM). The longitudinal diffusivity (lambda l), radial diffusivity (lambda r), and fractional anisotropy (FA) were obtained from each ROI. The underlying histopathology was then evaluated using immunofluorescent assay with antibodies directed to myelin and neurofilament staining. Results: The mean values for lambda l and lambda r were significantly elevated within HIL relative to NAWM and LIL. IFA analysis of HIL demonstrated significant demyellnation, without significant if any axon loss. The FA values were significantly reduced in HIL and LILs. FA values were also reduced in lesions with increased lambda l and lambda r values relative to normal. Conclusion: Aberrant lambda l, lambda r, and FA relative to normal values are strong indicators of demyelination. DTI indices are not specific for axon loss. IFA analysis is a reliable method to demonstrate myelin and axon pathology within the ex vivo setting.