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Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis

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Abstract

Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test–retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing–remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC) = 0.99, 95 % CI = 0.98–0.99) and interobserver agreement (ICC = 0.98, 95 % CI = 0.74–0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICC = 0.86, 95 % CI = 0.58–0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (p ≤ 0.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test–retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in MS.

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References

  1. Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, Kolb FP (2010) The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex 46(7):845–857. doi:10.1016/j.cortex.2009.06.009

    Article  PubMed  CAS  Google Scholar 

  2. Manto M-U (ed) (2010) Cerebellar disorders : a practical approach to diagnosis and management. Cambridge University Press, Cambridge

    Google Scholar 

  3. Eriksson M, Andersen O, Runmarker B (2003) Long-term follow up of patients with clinically isolated syndromes, relapsing–remitting and secondary progressive multiple sclerosis. Mult Scler 9(3):260–274

    Article  PubMed  Google Scholar 

  4. Miller DH, Hornabrook RW, Purdie G (1992) The natural history of multiple sclerosis: a regional study with some longitudinal data. J Neurol Neurosurg Psychiatr 55(5):341–346

    Article  PubMed  CAS  Google Scholar 

  5. Lycklama a Nijeholt G, Barkhof F (2003) Differences between subgroups of MS: MRI findings and correlation with histopathology. J Neurol Sci 206 (2):173–174

  6. Ceccarelli A, Rocca MA, Pagani E, Colombo B, Martinelli V, Comi G, Filippi M (2008) A voxel-based morphometry study of grey matter loss in MS patients with different clinical phenotypes. Neuroimage 42(1):315–322

    Article  PubMed  Google Scholar 

  7. Mesaros S, Rovaris M, Pagani E, Pulizzi A, Caputo D, Ghezzi A, Bertolotto A, Capra R, Falautano M, Martinelli V, Comi G, Filippi M (2008) A magnetic resonance imaging voxel-based morphometry study of regional gray matter atrophy in patients with benign multiple sclerosis. Arch Neurol 65(9):1223–1230

    Article  PubMed  Google Scholar 

  8. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33(3):341–355

    Article  PubMed  CAS  Google Scholar 

  9. Tae WS, Kim SS, Lee KU, Nam EC, Kim KW (2008) Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder. Neuroradiology 50(7):569–581. doi:10.1007/s00234-008-0383-9

    Article  PubMed  Google Scholar 

  10. Sanchez-Benavides G, Gomez-Anson B, Sainz A, Vives Y, Delfino M, Pena-Casanova J (2010) Manual validation of FreeSurfer’s automated hippocampal segmentation in normal aging, mild cognitive impairment, and Alzheimer disease subjects. Psychiatry Res 181(3):219–225. doi:10.1016/j.pscychresns.2009.10.011

    Article  PubMed  Google Scholar 

  11. Richter S, Matthies K, Ohde T, Dimitrova A, Gizewski E, Beck A, Aurich V, Timmann D (2004) Stimulus-response versus stimulus–stimulus-response learning in cerebellar patients. Exp Brain Res 158(4):438–449

    Article  PubMed  CAS  Google Scholar 

  12. Brandauer B, Hermsdorfer J, Beck A, Aurich V, Gizewski ER, Marquardt C, Timmann D (2008) Impairments of prehension kinematics and grasping forces in patients with cerebellar degeneration and the relationship to cerebellar atrophy. Clin Neurophysiol 119(11):2528–2537. doi:10.1016/j.clinph.2008.07.280

    Article  PubMed  CAS  Google Scholar 

  13. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    Article  PubMed  CAS  Google Scholar 

  14. Goebel R, Esposito F, Formisano E (2006) Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: from single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis. Hum Brain Mapp 27(5):392–401. doi:10.1002/hbm.20249

    Article  PubMed  Google Scholar 

  15. Aurich VaW J (1995) Non-linear Gaussian filters performing edge preserving diffusion. In: Proceedings 17. DAGM-Symposium, Springer, Bielefeld, pp 538–545

  16. Aurich V, Winkler G, Liebscher V (1999) Probabilistic image smoothing: recent advances. In: Benes V, Janacek J, Saxl I (eds) Proceedings S4G, International Conference on Stereology, Spatial Statistics and Stochastic Geometry, Prague. Union of Czech Mathematicians and Physicists, pp 273–278

  17. Beck A (2003) Ein System zur Verarbeitung und Visualisierung von Voxeldaten. Heinrich-Heine University of Düsseldorf, Düsseldorf

    Google Scholar 

  18. Aurich V, Beck A (2002) ECCET: Ein System zur 3D-Visualisierung von Volumendaten mit Echtzeitnavigation. In: Proceedings Workshops über Bildverarbeitung für die Medizin, Leipzig, pp 389–392

  19. 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

    Article  PubMed  Google Scholar 

  20. Jasperse B, Valsasina P, Neacsu V, Knol DL, De Stefano N, Enzinger C, Smith SM, Ropele S, Korteweg T, Giorgio A, Anderson V, Polman CH, Filippi M, Miller DH, Rovaris M, Barkhof F, Vrenken H (2007) Intercenter agreement of brain atrophy measurement in multiple sclerosis patients using manually-edited SIENA and SIENAX. J Magn Reson Imag 26(4):881–885

    Article  Google Scholar 

  21. Shrout PE, Fleiss JL (1979) Intraclass correlations—uses in assessing rater reliability. Psychol Bull 86(2):420–428

    Article  PubMed  CAS  Google Scholar 

  22. McGraw KO, Wong SP (1996) Forming inferences about some intraclass correlation coefficients. Psychol Methods 1(1):30–46

    Article  Google Scholar 

  23. Dimitrova A, Gerwig M, Brol B, Gizewski ER, Forsting M, Beck A, Aurich V, Kolb FP, Timmann D (2008) Correlation of cerebellar volume with eyeblink conditioning in healthy subjects and in patients with cerebellar cortical degeneration. Brain Res 1198:73–84. doi:10.1016/j.brainres.2008.01.034

    Article  PubMed  CAS  Google Scholar 

  24. Calabrese M, Mattisi I, Rinaldi F, Favaretto A, Atzori M, Bernardi V, Barachino L, Romualdi C, Rinaldi L, Perini P, Gallo P (2011) Magnetic resonance evidence of cerebellar cortical pathology in multiple sclerosis. J Neurol Neurosurg Psychiatr 81(4):401–404

    Article  Google Scholar 

  25. Anderson VM, Fisniku LK, Altmann DR, Thompson AJ, Miller DH (2009) MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction. Mult Scler 15(7):811–817

    Article  PubMed  CAS  Google Scholar 

  26. Dimitrova A, Zeljko D, Schwarze F, Maschke M, Gerwig M, Frings M, Beck A, Aurich V, Forsting M, Timmann D (2006) Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei. Neuroimage 30(1):12–25. doi:10.1016/j.neuroimage.2005.09.020

    Article  PubMed  CAS  Google Scholar 

  27. Richter S, Dimitrova A, Maschke M, Gizewski E, Beck A, Aurich V, Timmann D (2005) Degree of cerebellar ataxia correlates with three-dimensional MRI-based cerebellar volume in pure cerebellar degeneration. Eur Neurol 54(1):23–27. doi:10.1159/000087241

    Article  PubMed  Google Scholar 

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Conflicts of interest

A. Beck has developed the ECCET Toolkit, which is currently provided free of charge for research purposes by his company ‘Beck Datentechnik’. T. Derfuss served on advisory boards for Novartis, Merck-Serono, Bayer Schering, Biogen Idec, and TEVA. He received travel support from Biogen Idec, Bayer Schering, and Merck Serono. He received research and/or unrestricted grants from Novartis, Biogen Idec, Merck Serono, the German Research Foundation, the Swiss MS Society, and the European Union. L. Kappos has participated in the last 24 months as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include: Abbott, Actelion, Advancell, Allozyne, BaroFold, Bayer HealthCare Pharmaceuticals, Bayer Schering, Bayhill, Biogen Idec, BioMarin, CSL Behring, Elan, Genmab, Glenmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, Novartis, Novonordisk, Peptimmune, Sanofiaventis, Santhera, Roche, TEVA, UCB and Wyeth. D. Timmann received research support from the German Research Foundation (DFG), grants DFG Ti 239/9-1 and DFG TI 239/10-1, the European Union (Partner in one of the Marie Curie Initial Training Networks), the Bernd Fink Foundation and the German Heredoataxia Foundation. T. Sprenger served on advisory boards for Mitsubishi Pharma, Eli Lilly, Biogen and Allergan. He received travel support from Pfizer, Bayer Schering, Eli Lilly and Allergan. All remaining authors report no conflicts of interest.

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Correspondence to Katrin Weier.

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Weier, K., Beck, A., Magon, S. et al. Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis. J Neurol 259, 2673–2680 (2012). https://doi.org/10.1007/s00415-012-6569-4

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  • DOI: https://doi.org/10.1007/s00415-012-6569-4

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