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

• Published in: Multiple sclerosis Vol. 9; no. 6; pp. 566 - 573
• Main Authors: Traboulsee, A, Dehmeshki, J, Peters, Kevin R, Griffin, C M, Brex, P A, Silver, N, Ciccarrelli, O, Chard, D T, Barker, G J, Thompson, A J, Miller, D H
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01-12-2003; Arnold; Sage Publications Ltd
• Subjects: Adult; Atrophy; Biological and medical sciences; Brain - pathology; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disability Evaluation; Female; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - pathology; Neurology; histogram; magnetic resonance imaging; normal appearing brain tissue; MRI; brain atrophy; multiple sclerosis; MTR; magnetization transfer ratio; magnetization transfer imaging; Histogram; Relapse; Multiple sclerosis; Central nervous system; Cerebrospinal fluid; Multivariate analysis; Image; Variance; Inflammatory disease; Encephalon; MRI; magnetization transfer imaging; magnetization transfer ratio; brain atrophy; histogram; magnetic resonance imaging; Atrophy; Disability; Imaging; Size effect; Degenerative disease; Human; Nervous system diseases; Magnetization; Spin echo; Nuclear magnetic resonance imaging; Central nervous system disease; MTR; multiple sclerosis; normal appearing brain tissue; Transfer; Medical imagery; Lesion; Deviation; Comparative study
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1191/1352458503ms958oa

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.