Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities

Background: Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). A ims: 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NA BT MTR histograms. Methods: 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NA BT after extracting lesions and cerebrospinal fluid (C SF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. Results: MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NA BT mean MTR (± standard deviation) compared with controls (33.07 pu± 1.06 versus 34.26 pu± 0.47; P < 0.001) with an effect size of 2.56. The reductio n in NA BT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NA BT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r =0.58). EDSS score correlated with NA BT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r =0.59). Multivariate analysis using NA BT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r =0.62; P <0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r =0.72; P <0.001). Conclusions: There is evidence of diffuse abnormalities in NA BT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. A trophy, NA BT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

[1]  M Filippi,et al.  A magnetization transfer histogram study of normal-appearing brain tissue in MS , 2000, Neurology.

[2]  P S Tofts,et al.  Magnetization transfer imaging. , 2000, Neuroimaging clinics of North America.

[3]  G S Francis,et al.  Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[4]  N. Richert,et al.  Magnetization transfer imaging to monitor clinical trials in multiple sclerosis. , 1999, Neurology.

[5]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[6]  A. Thompson,et al.  T1 histograms of normal-appearing brain tissue are abnormal in early relapsing-remitting multiple sclerosis , 2002, Multiple Sclerosis.

[7]  P M Matthews,et al.  Axonal injury or loss in the internal capsule and motor impairment in multiple sclerosis. , 2000, Archives of neurology.

[8]  G. Barker,et al.  An interleaved sequence for accurate and reproducible clinical measurement of magnetization transfer ratio. , 1996, Magnetic resonance imaging.

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

[10]  F. Barkhof,et al.  MR outcome parameters in multiple sclerosis: comparison of surface-based thresholding segmentation and magnetization transfer ratio histographic analysis in relation to disability (a preliminary note). , 1998, AJNR. American journal of neuroradiology.

[11]  James M Provenzale,et al.  Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal-appearing white matter. , 2002, Radiology.

[12]  P Kapeller,et al.  Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis. , 2002, Brain : a journal of neurology.

[13]  Massimo Filippi,et al.  Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis , 2003, Journal of magnetic resonance imaging : JMRI.

[14]  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.

[15]  J. Dehmeshki,et al.  Magnetisation transfer ratio histogram analysis of primary progressive and other multiple sclerosis subgroups , 2001, Journal of the Neurological Sciences.

[16]  D.L. Plummer,et al.  DispImage: Un mezzo di analisi e presentazione per iconografia medica , 1992 .

[17]  A. Thompson,et al.  The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. , 1998, Brain : a journal of neurology.

[18]  B D Trapp,et al.  Axonal pathology in multiple sclerosis: relationship to neurologic disability. , 1999, Current opinion in neurology.

[19]  J K Udupa,et al.  Differences between relapsing-remitting and chronic progressive multiple sclerosis as determined with quantitative MR imaging. , 1999, Radiology.

[20]  David H. Miller,et al.  Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. , 2002, Brain : a journal of neurology.

[21]  Antonio Federico,et al.  Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability. , 2002, Archives of neurology.

[22]  B. Lewis,et al.  Characterization of differences between multiple sclerosis and normal brain: a global magnetization transfer application. , 1999, AJNR. American journal of neuroradiology.

[23]  Zografos Caramanos,et al.  Magnetization transfer can predict clinical evolution in patients with multiple sclerosis , 2002, Journal of Neurology.

[24]  G J Barker,et al.  Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations , 2001, Neurology.

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

[26]  G. Comi,et al.  Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. , 2000, AJNR. American journal of neuroradiology.

[27]  G. Barker,et al.  Variations in T1 and T2 relaxation times of normal appearing white matter and lesions in multiple sclerosis , 2000, Journal of the Neurological Sciences.

[28]  P M Matthews,et al.  Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. , 2002, Brain : a journal of neurology.

[29]  J K Udupa,et al.  Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis. , 2001, AJNR. American journal of neuroradiology.

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

[31]  S Ropele,et al.  Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis , 2002, Multiple sclerosis.

[32]  天野 康雄,et al.  骨髄病変に対する脂肪抑制法併用 magnetization transfer imaging の検討 , 1997 .

[33]  G. Barker,et al.  Normal-appearing brain tissue MTR histograms in clinically isolated syndromes suggestive of MS , 2002, Neurology.