Skip to main content
Log in

Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias

  • Review
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Magnetic resonance imaging (MRI) of the brain is of high interest for diagnosing and understanding degenerative ataxias. Here, we present state-of-the-art MRI methods to characterize structural alterations of the cerebellum and introduce initial experiments to show abnormalities in the cerebellar nuclei. Clinically, T1-weighted MR images are used to assess atrophy of the cerebellar cortex, the brainstem, and the spinal cord, whereas T2-weighted and PD-weighted images are typically employed to depict potential white matter lesions that may be associated with certain types of ataxias. More recently, attention has also focused on the characterization of the cerebellar nuclei, which are discernible on spatially highly resolved iron-sensitive MR images due to their relatively high iron content, including T2 *-weighted images, susceptibility-weighted images (SWI), effective transverse relaxation rate (R2 *) maps, and quantitative susceptibility maps (QSM). Among these iron-sensitive techniques, QSM reveals the best contrast between cerebellar nuclei and their surroundings. In particular, the gyrification of the dentate nuclei is prominently depicted, even at the clinically widely available field strength of 3 T. The linear relationship between magnetic susceptibility and local iron content allows for determination of iron deposition in cerebellar nuclei non-invasively. The increased signal-to-noise ratio of ultrahigh-field MRI (B0 ≥ 7 T) and advances in spatial normalization methods enable functional MRI (fMRI) at the level of the cerebellar cortex and cerebellar nuclei. Data from initial fMRI studies are presented in three common forms of hereditary ataxias (Friedreich’s ataxia, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6). Characteristic changes in the fMRI signal are discussed in the light of histopathological data and current knowledge of the underlying physiology of the fMRI signal in the cerebellum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Klockgether T. Update on degenerative ataxias. Curr Opin Neurol. 2011;24:339–45. doi:10.1097/WCO.0b013e32834875ba.

    Article  PubMed  Google Scholar 

  2. Seidel K, Siswanto S, Brunt ER, den Dunnen W, Korf HW, Rub U. Brain pathology of spinocerebellar ataxias. Acta Neuropathol. 2012;124:1–21. doi:10.1007/s00401-012-1000-x.

    Article  CAS  PubMed  Google Scholar 

  3. Koeppen AH, Mazurkiewicz JE. Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol. 2013;72:78–90. doi:10.1097/NEN.0b013e31827e5762.

    Article  CAS  PubMed  Google Scholar 

  4. Koeppen AH. The pathogenesis of spinocerebellar ataxia. Cerebellum. 2005;4:62–73. doi:10.1080/14734220510007950.

    Article  CAS  PubMed  Google Scholar 

  5. Scherzed W, Brunt ER, Heinsen H, de Vos RA, Seidel K, Burk K, et al. Pathoanatomy of cerebellar degeneration in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Cerebellum. 2012;11:749–60. doi:10.1007/s12311-011-0340-8.

    Article  CAS  PubMed  Google Scholar 

  6. Koeppen AH, Michael SC, Knutson MD, Haile DJ, Qian J, Levi S, et al. The dentate nucleus in Friedreich's ataxia: the role of iron-responsive proteins. Acta Neuropathol. 2007;114:163–73. doi:10.1007/s00401-007-0220-y.

    Article  CAS  PubMed  Google Scholar 

  7. Gierga K, Schelhaas HJ, Brunt ER, Seidel K, Scherzed W, Egensperger R, et al. Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites. Neuropathol Appl Neurobiol. 2009;35:515–27. doi:10.1111/j.1365-2990.2009.01015.x.

    Article  CAS  PubMed  Google Scholar 

  8. Donato SD, Mariotti C and Taroni F. Chapter 25 - Spinocerebellar ataxia type 1. In: H. S. Sankara and D. Alexandra, editors. Handb Clin Neurol. Elsevier; 2012. pp. 399-421.

  9. Ernst TM, Schlamann M, Timmann D. MRI aspects: conventional, SWI, DTI. In: Gruol DL, Koibuchi N, Manto M, Molinari J, Schmahmann D, Shen Y, editors. Essentials of cerebellum and cerebellar disorders: a primer for graduate students. Springer; in press.

  10. Burk K, Abele M, Fetter M, Dichgans J, Skalej M, Laccone F, et al. Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain J Neurol. 1996;119(Pt 5):1497–505.

    Article  Google Scholar 

  11. Klockgether T, Petersen D, Grodd W, Dichgans J. Early onset cerebellar ataxia with retained tendon reflexes. Clinical, electrophysiological and MRI observations in comparison with Friedreich's ataxia. Brain J Neurol. 1991;114(Pt 4):1559–73. doi:10.1093/brain/114.4.1559.

  12. Schulz JB, Borkert J, Wolf S, Schmitz-Hubsch T, Rakowicz M, Mariotti C, et al. Visualization, quantification and correlation of brain atrophy with clinical symptoms in spinocerebellar ataxia types 1, 3 and 6. NeuroImage. 2010;49:158–68. doi:10.1016/j.neuroimage.2009.07.027.

    Article  PubMed  Google Scholar 

  13. Wolf N. Ataxia in metabolic and white matter disorders. In: Boltshauser E, SchmahmannJ, editors. Cerebellar disorders in children Clinics in Developmental Medicine. London, Mac Keith Press; 2012. pp. 269-81.

  14. Schulz JB, Klockgether T, Petersen D, Jauch M, Muller-Schauenburg W, Spieker S, et al. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry. 1994;57:1047–56. doi:10.1136/jnnp.57.9.1047.

  15. Koeppen AH, Ramirez RL, Yu D, Collins SE, Qian J, Parsons PJ, et al. Friedreich's ataxia causes redistribution of iron, copper, and zinc in the dentate nucleus. Cerebellum (Lond Engl). 2012;11:845–60. doi:10.1007/s12311-012-0383-5.

    Article  CAS  Google Scholar 

  16. Reichenbach JR, Venkatesan R, Schillinger DJ, Kido DK, Haacke EM. Small vessels in the human brain: MR venography with deoxyhemoglobin as an intrinsic contrast agent. Radiology. 1997;204:272–7. doi:10.1148/radiology.204.1.9205259.

  17. Diedrichsen J, Maderwald S, Küper M, Thürling M, Rabe K, Gizewski ER, et al. Imaging the deep cerebellar nuclei: a probabilistic atlas and normalization procedure. NeuroImage. 2011;54:1786–94. doi:10.1016/j.neuroimage.2010.10.035.

    Article  CAS  PubMed  Google Scholar 

  18. Solbach K, Kraff O, Minnerop M, Beck A, Schols L, Gizewski ER, et al. Cerebellar pathology in Friedreich's ataxia: atrophied dentate nuclei with normal iron content. NeuroImage Clin. 2014;6:93–9. doi:10.1016/j.nicl.2014.08.018.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Stefanescu MR, Dohnalek M, Maderwald S, Thurling M, Minnerop M, Beck A, et al. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia. Brain J Neurol. 2015;138:1182–97. doi:10.1093/brain/awv064.

    Article  Google Scholar 

  20. Schweser F, Deistung A, Lehr BW, Reichenbach JR. Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: an approach to in vivo brain iron metabolism? NeuroImage. 2011;54:2789–807. doi:10.1016/j.neuroimage.2010.10.070.

    Article  PubMed  Google Scholar 

  21. Langkammer C, Schweser F, Krebs N, Deistung A, Goessler W, Scheurer E, et al. Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study. NeuroImage. 2012;62:1593–9. doi:10.1016/j.neuroimage.2012.05.049.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kuper M, Thurling M, Stefanescu R, Maderwald S, Roths J, Elles HG, et al. Evidence for a motor somatotopy in the cerebellar dentate nucleus—an FMRI study in humans. Hum Brain Mapp. 2012;33:2741–9. doi:10.1002/hbm.21400.

    Article  PubMed  Google Scholar 

  23. Lauritzen M, Mathiesen C, Schaefer K, Thomsen KJ. Neuronal inhibition and excitation, and the dichotomic control of brain hemodynamic and oxygen responses. NeuroImage. 2012;62:1040–50. doi:10.1016/j.neuroimage.2012.01.040.

    Article  PubMed  Google Scholar 

  24. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. NeuroImage. 2006;33:127–38. doi:10.1016/j.neuroimage.2006.05.056.

    Article  PubMed  Google Scholar 

  25. Schmahmann JD, Doyon J, McDonald D, Holmes C, Lavoie K, Hurwitz AS, et al. Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space. NeuroImage. 1999;10:233–60. doi:10.1006/nimg.1999.0459.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the German Research Foundation (DFG, RE1123/9-2, DE2516/1-1, TI239/17-1), an EU Marie Curie Initial Training Network (ITN) grant C7 (“Cerebellar-Cortical Control: Cells, Circuits, Computation, and Clinic”) and a seed grant awarded to A.D. by the Interdisciplinary Center for Clinical Research (IZKF) in Jena, Germany.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andreas Deistung.

Ethics declarations

Conflicts of Interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deistung, A., Stefanescu, M.R., Ernst, T.M. et al. Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias. Cerebellum 15, 21–25 (2016). https://doi.org/10.1007/s12311-015-0738-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-015-0738-9

Keywords

Navigation