Top

Published in:

01-08-2015 | Original Communication

Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis

Authors: Michael Amann, Athina Papadopoulou, Michaela Andelova, Stefano Magon, Nicole Mueller-Lenke, Yvonne Naegelin, Christoph Stippich, Ernst Wilhelm Radue, Oliver Bieri, Ludwig Kappos, Till Sprenger

Published in: Journal of Neurology | Issue 8/2015

Abstract

Magnetization transfer ratio (MTR) is a semi-quantitative measure that seems to correlate with the degree of myelin loss and generally tissue destruction in multiple sclerosis (MS). Our objective was to comprehensively assess the MTR of lesions and normal appearing (NA) tissue separately in the white matter (WM), the cortex, the thalamus and the basal ganglia (BG) and determine their relative contribution to disability. In this cross-sectional study 71 patients were included (59 with relapsing–remitting MS, 12 with secondary progressive MS). We used a three-dimensional MTR sequence with high spatial resolution, based on balanced steady-state free precession. Mean MTR was calculated for lesions and NA tissue separately for each tissue type. Lesional MTR was lower than normal-appearing MTR in WM, cortex and thalamus. In the regression analysis, MTR of cortical lesions (β = −0.23, p = 0.05) and MTR of WML (β = −0.21, p = 0.08) were related by trend to the expanded disability status scale. MTR of WML significantly predicted the paced auditory serial-addition test (β = 0.35, p = 0.004). MTR of normal-appearing tissue did not relate to any outcome. Our results suggest that MTR of lesions in the white matter and cortex rather than of normal-appearing tissue relates to disability in patients with MS.

Dousset V, Grossman RI, Ramer KN, Schnall MD, Young LH, Gonzalez-Scarano F, Lavi E, Cohen JA (1992) Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology 182(2):483–491CrossRefPubMed

van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama a Nijeholt GJ, van der Valk P, Polman CH, Thompson AJ, Barkhof F (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46(5):747–754CrossRefPubMed

Grimaud J, Barker GJ, Wang L, Lai M, MacManus DG, Webb SL, Thompson AJ, McDonald WI, Tofts PS, Miller DH (1999) Correlation of magnetic resonance imaging parameters with clinical disability in multiple sclerosis: a preliminary study. J Neurol 246(10):961–967CrossRefPubMed

Gass A, Barker GJ, Kidd D, Thorpe JW, MacManus D, Brennan A, Tofts PS, Thompson AJ, McDonald WI, Miller DH (1994) Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis. Ann Neurol 36(1):62–67. doi:10.1002/ana.410360113 CrossRefPubMed

Miki Y, Grossman RI, Udupa JK, van Buchem MA, Wei L, Phillips MD, Patel U, McGowan JC, Kolson DL (1999) Differences between relapsing-remitting and chronic progressive multiple sclerosis as determined with quantitative MR imaging. Radiology 210(3):769–774CrossRefPubMed

Rovaris M, Agosta F, Sormani MP, Inglese M, Martinelli V, Comi G, Filippi M (2003) Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study. Brain 126(Pt 10):2323–2332. doi:10.1093/brain/awg232 CrossRefPubMed

Santos AC, Narayanan S, de Stefano N, Tartaglia MC, Francis SJ, Arnaoutelis R, Caramanos Z, Antel JP, Pike GB, Arnold DL (2002) Magnetization transfer can predict clinical evolution in patients with multiple sclerosis. J Neurol 249(6):662–668. doi:10.1007/s00415-002-0686-4 CrossRefPubMed

Oreja-Guevara C, Charil A, Caputo D, Cavarretta R, Sormani MP, Filippi M (2006) Magnetization transfer magnetic resonance imaging and clinical changes in patients with relapsing-remitting multiple sclerosis. Arch Neurol 63(5):736–740. doi:10.1001/archneur.63.5.736 CrossRefPubMed

Tur C, Khaleeli Z, Ciccarelli O, Altmann DR, Cercignani M, Miller DH, Thompson AJ (2011) Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS. J Neurol Neurosurg Psychiatry 82(4):423–428. doi:10.1136/jnnp.2010.209890 CrossRefPubMed

10.

Ge Y, Grossman RI, Udupa JK, Babb JS, Kolson DL, McGowan JC (2001) Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 22(3):470–475PubMed

11.

Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M (2006) Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain 129(Pt 10):2620–2627. doi:10.1093/brain/awl208 CrossRefPubMed

12.

Barker GJ, Schreiber WG, Gass A, Ranjeva JP, Campi A, van Waesberghe JH, Franconi JM, Watt HC, Tofts PS (2005) A standardised method for measuring magnetisation transfer ratio on MR imagers from different manufacturers—the EuroMT sequence. Magma 18(2):76–80. doi:10.1007/s10334-004-0095-z CrossRefPubMed

13.

Cercignani M, Symms MR, Schmierer K, Boulby PA, Tozer DJ, Ron M, Tofts PS, Barker GJ (2005) Three-dimensional quantitative magnetisation transfer imaging of the human brain. Neuroimage 27(2):436–441. doi:10.1016/j.neuroimage.2005.04.031 CrossRefPubMed

14.

Bieri O, Scheffler K (2006) On the origin of apparent low tissue signals in balanced SSFP. Magn Reson Med 56(5):1067–1074. doi:10.1002/mrm.21056 CrossRefPubMed

15.

Bieri O, Scheffler K (2007) Optimized balanced steady-state free precession magnetization transfer imaging. Magn Reson Med 58(3):511–518. doi:10.1002/mrm.21326 CrossRefPubMed

16.

Tortorella P, Rocca MA, Mezzapesa DM, Ghezzi A, Lamantia L, Comi G, Filippi M (2006) MRI quantification of gray and white matter damage in patients with early-onset multiple sclerosis. J Neurol 253(7):903–907. doi:10.1007/s00415-006-0129-8 CrossRefPubMed

17.

Bendfeldt K, Kuster P, Traud S, Egger H, Winklhofer S, Mueller-Lenke N, Naegelin Y, Gass A, Kappos L, Matthews PM, Nichols TE, Radue EW, Borgwardt SJ (2009) Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis—a longitudinal voxel-based morphometry study. Neuroimage 45(1):60–67. doi:10.1016/j.neuroimage.2008.10.006 CrossRefPubMed

18.

Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA (2005) Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 236(1):254–260. doi:10.1148/radiol.2361040450 CrossRefPubMed

19.

Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29(3):162–173CrossRefPubMed

20.

Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208–S219. doi:10.1016/j.neuroimage.2004.07.051 CrossRefPubMed

21.

Zhang Y, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20(1):45–57. doi:10.1109/42.906424 CrossRefPubMed

22.

Patenaude B, Smith SM, Kennedy DN, Jenkinson M (2011) A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 56(3):907–922. doi:10.1016/j.neuroimage.2011.02.046 PubMedCentralCrossRefPubMed

23.

Geurts JJ, Roosendaal SD, Calabrese M, Ciccarelli O, Agosta F, Chard DT, Gass A, Huerga E, Moraal B, Pareto D, Rocca MA, Wattjes MP, Yousry TA, Uitdehaag BM, Barkhof F (2011) Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology 76(5):418–424. doi:10.1212/WNL.0b013e31820a0cc4 CrossRefPubMed

24.

Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5(4):244–250CrossRefPubMed

25.

Vrenken H, Geurts JJ, Knol DL, Polman CH, Castelijns JA, Pouwels PJ, Barkhof F (2006) Normal-appearing white matter changes vary with distance to lesions in multiple sclerosis. AJNR Am J Neuroradiol 27(9):2005–2011PubMed

26.

Dehmeshki J, Chard DT, Leary SM, Watt HC, Silver NC, Tofts PS, Thompson AJ, Miller DH (2003) The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study. J Neurol 250(1):67–74. doi:10.1007/s00415-003-0955-x CrossRefPubMed

27.

Hofman PA, Kemerink GJ, Jolles J, Wilmink JT (1999) Quantitative analysis of magnetization transfer images of the brain: effect of closed head injury, age and sex on white matter. Magn Reson Med 42(4):803–806CrossRefPubMed

28.

Laule C, Vavasour IM, Whittall KP, Oger J, Paty DW, Li DK, MacKay AL, Arnold DL (2003) Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis. J Neurol 250(8):924–931. doi:10.1007/s00415-003-1115-z CrossRefPubMed

29.

Kutzelnigg A, Lassmann H (2005) Cortical lesions and brain atrophy in MS. J Neurol Sci 233(1–2):55–59. doi:10.1016/j.jns.2005.03.027 CrossRefPubMed

30.

Davies GR, Altmann DR, Hadjiprocopis A, Rashid W, Chard DT, Griffin CM, Tofts PS, Barker GJ, Kapoor R, Thompson AJ, Miller DH (2005) Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis. J Neurol 252(9):1037–1044. doi:10.1007/s00415-005-0808-x CrossRefPubMed

31.

Vrenken H, Pouwels PJ, Ropele S, Knol DL, Geurts JJ, Polman CH, Barkhof F, Castelijns JA (2007) Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease. Mult Scler 13(6):708–716. doi:10.1177/1352458506075521 CrossRefPubMed

32.

Crespy L, Zaaraoui W, Lemaire M, Rico A, Faivre A, Reuter F, Malikova I, Confort-Gouny S, Cozzone PJ, Pelletier J, Ranjeva JP, Audoin B (2011) Prevalence of grey matter pathology in early multiple sclerosis assessed by magnetization transfer ratio imaging. PLoS One 6(9):e24969. doi:10.1371/journal.pone.0024969 PubMedCentralCrossRefPubMed

33.

Seewann A, Vrenken H, Kooi EJ, van der Valk P, Knol DL, Polman CH, Pouwels PJ, Barkhof F, Geurts JJ (2011) Imaging the tip of the iceberg: visualization of cortical lesions in multiple sclerosis. Mult Scler 17(10):1202–1210. doi:10.1177/1352458511406575 CrossRefPubMed

34.

Moll NM, Rietsch AM, Thomas S, Ransohoff AJ, Lee JC, Fox R, Chang A, Ransohoff RM, Fisher E (2011) Multiple sclerosis normal-appearing white matter: pathology-imaging correlations. Ann Neurol 70(5):764–773. doi:10.1002/ana.22521 PubMedCentralCrossRefPubMed

35.

Kalkers NF, Hintzen RQ, van Waesberghe JH, Lazeron RH, van Schijndel RA, Ader HJ, Polman CH, Barkhof F (2001) Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy. J Neurol Sci 184(2):155–162CrossRefPubMed

36.

Sharma J, Zivadinov R, Jaisani Z, Fabiano AJ, Singh B, Horsfield MA, Bakshi R (2006) A magnetization transfer MRI study of deep gray matter involvement in multiple sclerosis. J Neuroimaging 16(4):302–310. doi:10.1111/j.1552-6569.2006.00054.x CrossRefPubMed

37.

Filippi M, Bozzali M, Comi G (2001) Magnetization transfer and diffusion tensor MR imaging of basal ganglia from patients with multiple sclerosis. J Neurol Sci 183(1):69–72CrossRefPubMed

38.

Davies GR, Altmann DR, Rashid W, Chard DT, Griffin CM, Barker GJ, Kapoor R, Thompson AJ, Miller DH (2005) Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis. Mult Scler 11(3):276–281CrossRefPubMed

39.

Filippi M, Agosta F (2007) Magnetization transfer MRI in multiple sclerosis. J Neuroimaging 17(Suppl 1):22S–26S. doi:10.1111/j.1552-6569.2007.00132.x CrossRefPubMed

40.

Wattjes MP, Lutterbey GG, Gieseke J, Traber F, Klotz L, Schmidt S, Schild HH (2007) Double inversion recovery brain imaging at 3T: diagnostic value in the detection of multiple sclerosis lesions. AJNR Am J Neuroradiol 28(1):54–59PubMed

41.

Simon B, Schmidt S, Lukas C, Gieseke J, Traber F, Knol DL, Willinek WA, Geurts JJ, Schild HH, Barkhof F, Wattjes MP (2010) Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla. Eur Radiol 20(7):1675–1683. doi:10.1007/s00330-009-1705-y PubMedCentralCrossRefPubMed

42.

Khangure SR, Khangure MS (2011) MR imaging in multiple sclerosis: the accuracy of 3D double inversion recovery at 3 Tesla and the potential for single sequence imaging. Neuroradiol J 24(1):92–99CrossRefPubMed

43.

Vural G, Keklikoglu HD, Temel S, Deniz O, Ercan K (2013) Comparison of double inversion recovery and conventional magnetic resonance brain imaging in patients with multiple sclerosis and relations with disease disability. Neuroradiol J 26(2):133–142CrossRefPubMed

44.

Samson RS, Cardoso MJ, Muhlert N, Sethi V, Wheeler-Kingshott CA, Ron M, Ourselin S, Miller DH, Chard DT (2014) Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups. Mult Scler 20(10):1322–1330. doi:10.1177/1352458514522537 CrossRefPubMed

Title: Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis
Authors: Michael Amann
Athina Papadopoulou
Michaela Andelova
Stefano Magon
Nicole Mueller-Lenke
Yvonne Naegelin
Christoph Stippich
Ernst Wilhelm Radue
Oliver Bieri
Ludwig Kappos
Till Sprenger
Publication date: 01-08-2015
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 8/2015
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-015-7793-5

At a glance: The STEP trials

Springer Medicine

Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2015

Sustained-released fampridine in multiple sclerosis: effects on gait parameters, arm function, fatigue, and quality of life

Radiotherapy treatment of sialorrhea in patients with amyotrophic lateral sclerosis requiring non-invasive ventilation

Eye-tracking controlled cognitive function tests in patients with amyotrophic lateral sclerosis: a controlled proof-of-principle study

Neuroimaging evidence of gray and white matter damage and clinical correlates in progressive supranuclear palsy

Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies

Unchanged gastric emptying and visceral perception in early Parkinson's disease after a high caloric test meal