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Brain Advance Access originally published online on June 8, 2007
Brain 2007 130(8):2199-2210; doi:10.1093/brain/awm122
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

High resolution diffusion tensor imaging of axonal damage in focal inflammatory and demyelinating lesions in rat spinal cord

Cynthia A. DeBoy1, Jiangyang Zhang2, Sonny Dike3, Irina Shats3, Melina Jones1, Daniel S. Reich1,2, Susumu Mori2, Thien Nguyen1, Brian Rothstein4, Robert H. Miller4, John T. Griffin1,5, Douglas A. Kerr1,3 and Peter A. Calabresi1

1Department of Neurology, Johns Hopkins University, School of Medicine, 2Department of Radiology, Johns Hopkins University, School of Medicine, 3Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health and Hygiene, 4Department of Neurosciences, Case Western Reserve University and 5Department of Neuroscience, Johns Hopkins University, School of Medicine

Correspondence to: Peter A. Calabresi, MD, Pathology Building, Suite 627, Johns Hopkins Hospital, 600 N. Wolfe St, Baltimore, MD 21287, USA E-mail: calabresi{at}jhmi.edu

Inflammation, demyelination, gliosis and axonal degeneration are pathological hallmarks of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis. Axonal damage is thought to contribute to irreversible damage and functional impairment, but is difficult to quantify. Conventional MRI has been used to assess the inflammatory and demyelinating aspects of MS lesions, but more sensitive and specific methods are needed to identify axonal damage to monitor disease progression and to determine efficacy of putative neuroprotective agents. We used high resolution diffusion tensor imaging (DTI) and fibre tracking to examine the spinal cord in rats with focal dorsal column inflammatory or demyelinating lesions to determine whether DTI measures can be used to detect pathology at the site of the focal lesion and to measure axonal damage in tracts distal to the focal lesion. Distant from the focal lesion, total axon counts, degenerating axon counts and SMI-31 staining, but not Luxol fast blue staining, were significantly correlated with fractional anisotropy, axial diffusivity and radial diffusivity, all of which are derived from the DTI data. These data suggest that high resolution DTI may be a more sensitive method than conventional imaging for detecting axonal damage at sites distant from inflammation.

Key Words: Demyelinating disease; Neuroimaging; Spinal cord; MRI; Axonal degeneration

Abbreviations: {lambda}||, axial diffusivity; {lambda}{perp}, radial diffusivity; DTI, diffusion tensor imaging; FA, fractional anisotropy

Received January 17, 2007. Revised March 30, 2007. Accepted May 1, 2007.


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