Toward accurate diagnosis of white matter pathology using diffusion tensor imaging

Diffusion tensor imaging (DTI) has been widely applied to investigate injuries in the central nervous system (CNS) white matter (WM). However, the underlying pathological correlates of diffusion changes have not been adequately determined. In this study the coregistration of histological sections to MR images and a pixel‐based receiver operating characteristic (ROC) analysis were used to compare the axial (λ∥) and radial (λ⟂) diffusivities derived from DTI and histological markers of axon (phosphorylated neurofilament, SMI‐31) and myelin (Luxol fast blue (LFB)) integrity, respectively, in two different patterns of injury to mouse spinal cord (SC) WM. In contusion SC injury (SCI), a decrease in λ∥ matched the pattern of axonal damage with high accuracy, but λ⟂ did not match the pattern of demyelination detected by LFB. In a mouse model of multiple sclerosis (MS), λ⟂ and λ∥ did not match the patterns of demyelination or axonal damage, respectively. However, a region of interest (ROI) analysis suggested that λ⟂‐detected demyelination paralleled that observed with LFB, and λ∥ decreased in both regions of axonal damage and normal‐appearing WM (NAWM) as visualized by SMI‐31. The results suggest that directional diffusivities may reveal abnormalities that are not obvious with SMI‐31 and LFB staining, depending on the type of injury. Magn Reson Med 57:688–695, 2007. © 2007 Wiley‐Liss, Inc.

[1]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[2]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[3]  I. Griffiths,et al.  Nerve fibres in spinal cord impact injuries Part 1. Changes in the myelin sheath during the initial 5 weeks , 1983, Journal of the Neurological Sciences.

[4]  Fred L. Bookstein,et al.  Principal Warps: Thin-Plate Splines and the Decomposition of Deformations , 1989, IEEE Trans. Pattern Anal. Mach. Intell..

[5]  S. Finkelstein,et al.  Experimental spinal cord injury: qualitative and quantitative histopathologic evaluation. , 1990, Journal of neurotrauma.

[6]  M. Fehlings,et al.  The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury , 1995, Experimental Neurology.

[7]  M. Beattie,et al.  Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats , 1997, Journal of neuroscience research.

[8]  D. Peck,et al.  Registration and warping of magnetic resonance images to histological sections. , 1999, Medical physics.

[9]  A. Cross,et al.  Dual Role for Fas Ligand in the Initiation of and Recovery from Experimental Allergic Encephalomyelitis , 1999, The Journal of experimental medicine.

[10]  H. Lassmann,et al.  Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. , 2000, The American journal of pathology.

[11]  R. Dzwonczyk,et al.  Traumatic spinal cord injury produced by controlled contusion in mouse. , 2000, Journal of neurotrauma.

[12]  M. Schwab,et al.  Reactions of Oligodendrocytes to Spinal Cord Injury: Cell Survival and Myelin Repair , 2000, Experimental Neurology.

[13]  R. Rudick,et al.  Neurological disability correlates with spinal cord axonal loss and reduced N‐acetyl aspartate in chronic multiple sclerosis patients , 2000, Annals of neurology.

[14]  Manabu Onuki,et al.  Axonal degeneration is an early pathological feature in autoimmune‐mediated demyelination in mice , 2001, Microscopy research and technique.

[15]  B. Trapp,et al.  Axon Loss in the Spinal Cord Determines Permanent Neurological Disability in an Animal Model of Multiple Sclerosis , 2002, Journal of neuropathology and experimental neurology.

[16]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[17]  B. Trapp,et al.  Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease , 2003, Journal of the Neurological Sciences.

[18]  E. D. Schwartz,et al.  Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF , 2003, Experimental Neurology.

[19]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[20]  Sheng-Kwei Song,et al.  A simple, robust hardware device for passive or active respiratory gating in MRI and MRS experiments , 2004 .

[21]  L. L. Cook,et al.  In vivo 4.0‐T magnetic resonance investigation of spinal cord inflammation, demyelination, and axonal damage in chronic‐progressive experimental allergic encephalomyelitis , 2004, Journal of magnetic resonance imaging : JMRI.

[22]  Michael Unser,et al.  Elastic registration of biological images using vector-spline regularization , 2005, IEEE Transactions on Biomedical Engineering.

[23]  Yaniv Assaf,et al.  Improved detectability of experimental allergic encephalomyelitis in excised swine spinal cords by high b-value q-space DWI , 2005, Experimental Neurology.

[24]  Abbas F Jawad,et al.  MRI diffusion coefficients in spinal cord correlate with axon morphometry , 2005, Neuroreport.

[25]  B. Reisberg,et al.  Diffusion Tensor Imaging of Frontal White Matter Microstructure in Early Alzheimer’s Disease: A Preliminary Study , 2005, Journal of geriatric psychiatry and neurology.

[26]  E. D. Schwartz,et al.  Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats. , 2005, AJNR. American journal of neuroradiology.

[27]  Roee S. Lazebnik,et al.  Three-Dimensional Registration of Magnetic Resonance Image Data to Histological Sections with Model-Based Evaluation , 2005, Annals of Biomedical Engineering.

[28]  J. Wrathall,et al.  Chronic alterations in the cellular composition of spinal cord white matter following contusion injury , 2005, Glia.

[29]  Jun Yoshino,et al.  Demyelination increases radial diffusivity in corpus callosum of mouse brain , 2005, NeuroImage.

[30]  L. L. Cook,et al.  Pathology‐guided MR analysis of acute and chronic experimental allergic encephalomyelitis spinal cord lesions at 1.5T , 2005, Journal of magnetic resonance imaging : JMRI.

[31]  David L Wilson,et al.  Correcting spatial distortion in histological images. , 2005, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[32]  Michael P. Harms,et al.  Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging , 2006, Experimental Neurology.

[33]  K. Hasan,et al.  In vivo serial diffusion tensor imaging of experimental spinal cord injury , 2006, Journal of neuroscience research.

[34]  Hsiao-Fang Liang,et al.  Detecting axon damage in spinal cord from a mouse model of multiple sclerosis , 2006, Neurobiology of Disease.

[35]  D. Pham‐Dinh,et al.  Axon loss is responsible for chronic neurological deficit following inflammatory demyelination in the rat , 2006, Experimental Neurology.

[36]  D. Larkman,et al.  Axial and Radial Diffusivity in Preterm Infants Who Have Diffuse White Matter Changes on Magnetic Resonance Imaging at Term-Equivalent Age , 2006, Pediatrics.

[37]  P. Poulet,et al.  Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging , 2006, Journal of neuroscience research.

[38]  Luis Concha,et al.  Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients , 2006, NeuroImage.

[39]  J. Michael Tyszka,et al.  Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant , 2006, NeuroImage.