Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis

Background: Cognitive impairment is one of the frequent and early findings in multiple sclerosis (MS). Objective: To determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage in the corpus callosum (CC), revealed by conventional magnetic resonance imaging (MRI), magnetisation transfer imaging (MTI) and diffusion tensor imaging (DTI). Methods: Conventional dual-echo, DTI and MTI of the brain were obtained from 36 patients with relapsing remitting (RR) MS, and 13 age and gender matched normal controls. Voxels from CC were identified using a tractography based algorithm. Mean apparent diffusion coefficient (ADCav) and MT ratio were measured for the CC as defined by tractography. Corpus callosum area (CCA) was measured using edge detection on the mid-sagittal slice on high resolution MRI images. The Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were scored. Results: Nine patients (25%) were found to be cognitively impaired. The CCA was not significantly different in the whole cohort of patients from controls (608.2 (428.6–713.0) mm2 vs 674.2 (585.8–754.4) mm2, p = 0.1), but was smaller in cognitively impaired than unimpaired group (417 (290–634) mm2 vs 652 (511–718) mm2, p = 0.04). The mean MT ratio of CC in patients was lower than in controls (0.41 (0.39–0.042) vs 0.43 (0.42–0.43), p<0.001). The ADCav in the CC in patients was higher than in controls (0.94 (0.89–0.99) vs 0.87 (0.85–0.89), p<0.001). PASAT was correlated with mean MT ratio (r = 0.47, p = 0.0046), ADCav (r = −0.53, p = 0.0012), CCA (r = 0.42, p = 0.01) and total T2 lesion load (r = −0.4, p = 0.017), but not with T2 lesion load within the CC (r = −0.24, p = 0.16), disease duration (r = −0.2, p = 0.24) or EDSS (r = −0.27, p = 0.12). Conclusions: ADCav, MTR and atrophy measures in the CC may offer a sensitive method detecting subtle macroscopic and microscopic changes associated with cognitive impairment in MS.

[1]  D. Gronwall.  Paced Auditory Serial-Addition Task: A Measure of Recovery from Concussion , 1977, Perceptual and motor skills.

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

[3]  V. Haughton,et al.  Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis , 1989, Neurology.

[4]  J. Taveras,et al.  Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis. , 1991, Radiology.

[5]  Milan Sonka,et al.  Image Processing, Analysis and Machine Vision , 1993, Springer US.

[6]  M. Poncet,et al.  Functional and magnetic resonance imaging correlates of callosal involvement in multiple sclerosis. , 1993, Archives of neurology.

[7]  J. Hogg.  Magnetic resonance imaging. , 1994, Journal of the Royal Naval Medical Service.

[8]  H. Fukuyama,et al.  Callosal Atrophy in Patients With Lacunar Infarction and Extensive Leukoaraiosis: An Indicator of Cognitive Impairment , 1994, Stroke.

[9]  L. Amaducci,et al.  Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up. , 1995, Archives of neurology.

[10]  J Foong,et al.  Executive function in multiple sclerosis. The role of frontal lobe pathology. , 1997, Brain : a journal of neurology.

[11]  J K Udupa,et al.  Correlation of volumetric magnetization transfer imaging with clinical data in MS , 1998, Neurology.

[12]  P. Basser,et al.  A simplified method to measure the diffusion tensor from seven MR images , 1998, Magnetic resonance in medicine.

[13]  J. K. Udupa,et al.  Isolated U-fiber involvement in MS , 1998, Neurology.

[14]  S. Reingold,et al.  The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment , 1999, Multiple sclerosis.

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

[16]  A. Thompson,et al.  Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates. , 1999, Brain : a journal of neurology.

[17]  R I Grossman,et al.  MR lesion load and cognitive function in patients with relapsing-remitting multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[18]  M Filippi,et al.  Normal-appearing white matter changes in multiple sclerosis: the contribution of magnetic resonance techniques , 1999, Multiple sclerosis.

[19]  M Rovaris,et al.  Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. , 2000, AJNR. American journal of neuroradiology.

[20]  M Rovaris,et al.  Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[21]  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.

[22]  J. Foong,et al.  A comparison of neuropsychological deficits in primary and secondary progressive multiple sclerosis , 2000, Journal of Neurology.

[23]  C H Polman,et al.  The Brief Repeatable Battery of Neuropsychological Tests: normative values allow application in multiple sclerosis clinical practice , 2001, Multiple sclerosis.

[24]  L. Blumhardt,et al.  Inflammation and atrophy in multiple sclerosis: MRI associations with disease course , 2001, Journal of the Neurological Sciences.

[25]  R. Zivadinov,et al.  MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis , 2001, Neuroradiology.

[26]  M Cercignani,et al.  Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[27]  P S Morgan,et al.  Quantitative diffusion weighted magnetic resonance imaging, cerebral atrophy, and disability in multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[28]  L D Blumhardt,et al.  Cognitive correlates of supratentorial atrophy on MRI in multiple sclerosis , 2001, Acta neurologica Scandinavica.

[29]  G Cazzato,et al.  A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[30]  Massimo Filippi,et al.  Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis , 2001, Journal of the Neurological Sciences.

[31]  P. Morgan,et al.  White matter mapping using diffusion tensor MRI , 2002, Magnetic resonance in medicine.

[32]  Paul S. Morgan,et al.  T1 relaxation time mapping of white matter tracts in multiple sclerosis defined by diffusion tensor imaging , 2002, Journal of Neurology.

[33]  M. Rovaris,et al.  Cognitive dysfunction in patients with mildly disabling relapsing–remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging , 2002, Journal of the Neurological Sciences.

[34]  A J Thompson,et al.  Brain atrophy in clinically early relapsing-remitting multiple sclerosis. , 2002, Brain : a journal of neurology.

[35]  Yamna Satgunasingam.  Executive function in Multiple Sclerosis , 2003 .

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

[37]  V. Wedeen,et al.  Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo , 2003, Magnetic resonance in medicine.

[38]  Paul S. Morgan,et al.  Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis , 2003, Journal of Neurology.

[39]  A Achiron,et al.  Cognitive impairment in probable multiple sclerosis , 2003, Journal of neurology, neurosurgery, and psychiatry.

[40]  Cris S Constantinescu,et al.  Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis--a quantitative T1 relaxation time mapping approach. , 2003, Journal of neurology.

[41]  R. Bowtell,et al.  Correction of spatial distortion in EPI due to inhomogeneous static magnetic fields using the reversed gradient method , 2004, Journal of magnetic resonance imaging : JMRI.

[42]  Jens Frahm,et al.  Multicontrast MRI of remyelination in the central nervous system , 2005, NMR in biomedicine.

[43]  Simon K Warfield,et al.  Diffusion Tensor Magnetic Resonance Imaging in Multiple Sclerosis , 2005, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[44]  M. Rovaris,et al.  “Importance sampling”: A strategy to overcome the clinical/MRI paradox in MS? , 2005, Journal of the Neurological Sciences.

[45]  H. Amièva,et al.  Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[46]  A. Thompson,et al.  A longitudinal study of cognition in primary progressive multiple sclerosis. , 2005, Brain : a journal of neurology.

[47]  P. Morgan,et al.  ‘Importance sampling’ in MS: Use of diffusion tensor tractography to quantify pathology related to specific impairment , 2005, Journal of the Neurological Sciences.

[48]  Bertrand Audoin,et al.  Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis , 2005, Human brain mapping.

[49]  F Barkhof,et al.  Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis , 2005, Multiple sclerosis.

[50]  Maria Assunta Rocca,et al.  A method for obtaining tract-specific diffusion tensor MRI measurements in the presence of disease: application to patients with clinically isolated syndromes suggestive of multiple sclerosis , 2005, NeuroImage.