Mean diffusivity and fractional anisotropy histogram analysis of the cervical cord in MS patients

The spinal cord is frequently involved in multiple sclerosis (MS), and cord damage may be an important contributor to disability. Diffusion tensor magnetic resonance imaging (DT-MRI) provides quantitative information about the structural and orientational features of the central nervous system. In order to assess whether diffusion tensor-derived measures of cord tissue damage are related to clinical disability, mean diffusivity (MD) and fractional anisotropy (FA) histograms from the cervical cord were acquired from a large cohort of MS patients. Diffusion-weighted sensitivity-encoded (SENSE) echo planar images of the cervical cord, and brain dual-echo and diffusion-weighted scans were acquired from 44 patients with MS and 17 healthy controls. Cord and brain MD and FA histograms were produced. An analysis of variance model, adjusting for cord volume and patient age, was used to compare cord DT-MRI parameters from controls and patients. A multivariate linear regression model was used to identify DT-MRI variables independently associated with disability. Average cervical cord FA was significantly lower in MS patients compared to controls. Cord cross-sectional area, average FA and average MD were all significantly correlated with the degree of disability (r values ranging from 0.36 to 0.51). The multivariate linear regression model retained average cord FA and average brain MD as variables independently associated with disability, with a correlation coefficient of 0.73 (P < 0.001). DT-MRI reveals a loss of cervical cord tissue structure in MS patients. The strong correlation found between a composite DT-MRI score and disability suggests that a full and accurate assessment of cervical cord damage in MS provides information that usefully contributes to an explanation of the clinical manifestations of the disease.

[1]  R. Ordidge,et al.  High field MRI correlates of myelin content and axonal density in multiple sclerosis , 2003, Journal of Neurology.

[2]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[3]  M Filippi,et al.  The role of non-conventional magnetic resonance techniques in monitoring evolution of multiple sclerosis. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[4]  Massimo Filippi,et al.  Spinal-cord MRI in multiple sclerosis , 2003, The Lancet Neurology.

[5]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[6]  M. Rovaris,et al.  Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[7]  David H. Miller,et al.  Diffusion imaging of the spinal cord in vivo: Estimation of the principal diffusivities and application to multiple sclerosis , 2000, Magnetic resonance in medicine.

[8]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[9]  M Cercignani,et al.  Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers. , 2000, AJNR. American journal of neuroradiology.

[10]  P. Matthews,et al.  Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. , 2000, Brain : a journal of neurology.

[11]  M. Horsfield,et al.  Sensitivity-encoded diffusion tensor MR imaging of the cervical cord. , 2003, AJNR. American journal of neuroradiology.

[12]  M. Esiri,et al.  Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. , 2004, Brain : a journal of neurology.

[13]  A. Thompson,et al.  Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. , 1996, Brain : a journal of neurology.

[14]  I. Allen,et al.  A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis , 1979, Journal of the Neurological Sciences.

[15]  F. Ikuta,et al.  Distribution of plaques in seventy autopsy cases of multiple sclerosis in the United States , 1976, Neurology.

[16]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[17]  G. Comi,et al.  Comparison of three MR sequences for the detection of cervical cord lesions in patients with multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[18]  A. Thompson,et al.  Improved imaging of the spinal cord in multiple sclerosis using three-dimensional fast spin echo , 1998, Neuroradiology.

[19]  F Barkhof,et al.  Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions , 2002, Neurology.

[20]  C. Mainero,et al.  Correlates of MS disability assessed in vivo using aggregates of MR quantities , 2001, Neurology.

[21]  Massimo Filippi,et al.  The use of quantitative magnetic-resonance-based techniques to monitor the evolution of multiple sclerosis , 2003, The Lancet Neurology.

[22]  G. Comi,et al.  In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. , 2001, Brain : a journal of neurology.

[23]  Massimo Filippi,et al.  A spinal cord MRI study of benign and secondary progressive multiple sclerosis , 2004, Journal of Neurology.

[24]  Gareth J. Barker,et al.  Investigating Cervical Spinal Cord Structure Using Axial Diffusion Tensor Imaging , 2002, NeuroImage.

[25]  D L Hill,et al.  Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. , 1997, Medical physics.

[26]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[27]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

[28]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[29]  L. Laitinen,et al.  Studies on the pathogenesis of multiple sclerosis. Participation of lysosomes on demyelination in the central nervous system white matter outside plaques. , 1973, European neurology.

[30]  G. Barker,et al.  Spinal cord atrophy and disability in MS , 1998, Neurology.

[31]  R. Knobler,et al.  Multiple sclerosis in the spinal cord: MR appearance and correlation with clinical parameters. , 1995, Radiology.

[32]  A. Thompson,et al.  Spinal cord MRI using multi‐array coils and fast spin echo , 1993, Neurology.

[33]  F. Barkhof,et al.  Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. , 2001, Brain : a journal of neurology.

[34]  Chris A Clark,et al.  Diffusion tensor imaging in spinal cord: methods and applications – a review , 2002, NMR in biomedicine.

[35]  M Cercignani,et al.  Diffusion tensor magnetic resonance imaging in multiple sclerosis , 2001, Neurology.

[36]  F. Barkhof,et al.  Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. , 1998, Brain : a journal of neurology.

[37]  M. Palkovits,et al.  Axonal changes in chronic demyelinated cervical spinal cord plaques. , 2000, Brain : a journal of neurology.

[38]  D. Prayer,et al.  Spinal cord lesions in patients with multiple sclerosis: comparison of MR pulse sequences. , 1996, AJNR. American journal of neuroradiology.