Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations

Objective: To quantitatively investigate water diffusion changes in normal-appearing white matter (NAWM) and gray matter in patients with MS, and to evaluate whether these changes are correlated with clinical disability and disease duration. Background: Diffusion tensor imaging provides quantitative information about the magnitude and directionality (anisotropy) of water diffusion in vivo and detects pathologic changes in MS brain tissue. Methods: Diffusion tensor imaging was performed in 39 patients with MS and in 21 age-matched control subjects. Quantitative indices, including fractional anisotropy, volume ratio, and mean diffusivity, were obtained in 30 regions of interest located in normal-appearing basal ganglia, cerebellar gray matter, and supratentorial and infratentorial NAWM. Results: Patients with MS showed significantly reduced anisotropy and a trend toward increased diffusivity in the infratentorial and supratentorial NAWM, and significantly increased anisotropy in the basal ganglia. In all patients with MS, both fractional anisotropy and mean diffusivity in the cerebral peduncles were inversely correlated with the Expanded Disability Status Scale and pyramidal functional scores. In patients with relapsing-remitting MS, there was a strong correlation between Expanded Disability Status Scale score and fractional anisotropy in both supratentorial and infratentorial NAWM. In primary and secondary progressive MS, disease duration correlated strongly with mean diffusivity in infratentorial NAWM and fractional anisotropy in the cerebral peduncles, respectively. Conclusion: The most striking finding of decreased fractional anisotropy in supratentorial and infratentorial NAWM and increased fractional anisotropy in basal ganglia may result from axonal degeneration due to fiber transection in remote focal lesions. Diffusion tensor imaging indices, in particular fractional anisotropy, appear sensitive to structural damage in NAWM that is associated with disability and progression in MS.

[1]  Symms,et al.  The pathogenesis of lesions and normal appearing white matter changes in multiple sclerosis: A serial diffusion magnetic resonance imaging study , 2000 .

[2]  J S Thornton,et al.  Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia. , 1997, Magnetic resonance imaging.

[3]  P M Matthews,et al.  Imaging axonal damage of normal-appearing white matter in multiple sclerosis. , 1998, Brain : a journal of neurology.

[4]  F. Fazio,et al.  Functional Basis of Memory Impairment in Multiple Sclerosis: A [18F]FDG PET Study , 1996, NeuroImage.

[5]  M Filippi,et al.  A Magnetization Transfer Imaging Study of Normal-Appearing White Matter in Multiple Sclerosis , 1995, Neurology.

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

[7]  G. Barker,et al.  Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis , 1999, Neurology.

[8]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[9]  M Cercignani,et al.  A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging. , 2000, Archives of neurology.

[10]  Nikos Evangelou,et al.  Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis , 2000, Annals of neurology.

[11]  M Xue,et al.  Postictal Alteration of Sodium Content and Apparent Diffusion Coefficient in Epileptic Rat Brain Induced by Kainic Acid , 1996, Epilepsia.

[12]  R. Kikinis,et al.  Magnetic resonance imaging shows orientation and asymmetry of white matter fiber tracts , 1998, Brain Research.

[13]  C. Pierpaoli,et al.  Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI. , 1999, Magnetic resonance imaging.

[14]  M S Buchsbaum,et al.  Whole-brain diffusion MR histograms differ between MS subtypes , 2000, Neurology.

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

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

[17]  I. Moseley,et al.  Signal intensity on MRI of basal ganglia in multiple sclerosis. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[18]  A. Thompson,et al.  Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. , 1995, Brain : a journal of neurology.

[19]  G J Barker,et al.  The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study. , 2000, Brain : a journal of neurology.

[20]  R. Kinkel,et al.  A Wallerian degeneration pattern in patients at risk for MS , 2000, Neurology.

[21]  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.

[22]  David H. Miller,et al.  Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance , 1996, Magnetic resonance in medicine.

[23]  M. I. Smith,et al.  A study of rotationally invariant and symmetric indices of diffusion anisotropy. , 1999, Magnetic resonance imaging.

[24]  M Brant-Zawadzki,et al.  Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration. , 1990, Archives of general psychiatry.

[25]  John T. O'Brien,et al.  White Matter Changes in Depression and Alzheimer's Disease: A Review of Magnetic Resonance Imaging Studies , 1996 .

[26]  A. Compston,et al.  Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. , 1996, Brain : a journal of neurology.

[27]  M Takasaki,et al.  Increased water diffusion in cerebral white matter in Alzheimer's disease. , 1997, Gerontology.

[28]  R. Tarducci,et al.  Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients. , 1999, Brain : a journal of neurology.

[29]  C. Thomsen,et al.  Increased water self‐diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis , 1993, Acta neurologica Scandinavica.

[30]  R Stollberger,et al.  Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis , 2000, Magnetic resonance in medicine.

[31]  G. Barker,et al.  1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis , 1997, Journal of neurology, neurosurgery, and psychiatry.

[32]  W. Ammann,et al.  Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue , 1997, Neurology.

[33]  W. Mcdonald,et al.  The longstanding MS lesion. A quantitative MRI and electron microscopic study. , 1991, Brain : a journal of neurology.

[34]  R. Kronmal,et al.  Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. , 1997, Stroke.

[35]  C. Thomsen,et al.  In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis. , 1992, Magnetic resonance imaging.

[36]  M. Gaviria,et al.  Vascular dementia, hypertension, and the brain. , 1997, Neurological research.

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

[38]  David H. Miller,et al.  Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke , 2000, Journal of neurology, neurosurgery, and psychiatry.

[39]  S. Reingold,et al.  The role of magnetic resonance techniques in understanding and managing multiple sclerosis. , 1998, Brain : a journal of neurology.

[40]  W R Kinkel,et al.  High‐Resolution Fluorodeoxyglucose Positron Emission Tomography Shows Both Global and Regional Cerebral Hypometabolism in Multiple Sclerosis , 1998, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[41]  R. Turner,et al.  Diffusion MR imaging: clinical applications. , 1992, AJR. American journal of roentgenology.

[42]  B. Brownell,et al.  The distribution of plaques in the cerebrum in multiple sclerosis , 1962, Journal of neurology, neurosurgery, and psychiatry.

[43]  F. Barkhof,et al.  Cortical lesions in multiple sclerosis. , 1999, Brain : a journal of neurology.

[44]  Stephen M. Rao White Matter Disease and Dementia , 1996, Brain and Cognition.

[45]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

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

[47]  G. E. Alexander,et al.  Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. , 1990, Progress in brain research.

[48]  W. Smoker,et al.  Cortical and subcortical T2 shortening in multiple sclerosis. , 1997, AJNR. American journal of neuroradiology.

[49]  G. Comi,et al.  Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI , 2000, Neurology.