Demyelinated lesions in the white matter of the brain and spinal cord are the pathological hallmark of the autoimmune disorder Multiple Sclerosis (MS). Active lesions, as observed in gadolinium (Gd) enhanced T1- weighted MRI, exhibit varying degrees of inflammation, demyelination, and axonal damage upon histological examination. The objective of the proposed study is to determine the time-course of inflammation, demyelination, and axonal damage and their contribution to lesion formation and progression. A longitudinal, in vivo investigation of the spinal cord in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, will be examined using MRI. Inflammation and breakdown of the blood-brain barrier will be assessed using magnetically loaded T-cells and Gd-enhancement, respectively (Aim 1). The extent of demyelination and axonal damage will be assessed using diffusion tensor imaging (Aim 2). All in vivo MRI findings will be correlated with neurological disability and validated with ex vivo MRI and histological analysis. The research will enhance the understanding of the dynamic pathological changes in EAE and MS and will assess the use of DTI as a diagnostic tool. ? ?
|Budde, Matthew D; Frank, Joseph A (2010) Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke. Proc Natl Acad Sci U S A 107:14472-7|
|Budde, Matthew D; Xie, Mingqiang; Cross, Anne H et al. (2009) Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: a quantitative pixelwise analysis. J Neurosci 29:2805-13|
|Budde, Matthew D; Kim, Joong Hee; Liang, Hsiao-Fang et al. (2007) Toward accurate diagnosis of white matter pathology using diffusion tensor imaging. Magn Reson Med 57:688-95|