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Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Medicine

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Published: July 28th, 2013

DOI:

10.3791/50427

1Department of Neurology, University of Ulm

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls.

DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.

In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging in the human brain

The white matter (WM) tracts in the central nervous system consist of densely packed axons in addition to various types of neuroglia and other small populations of cells. The axonal membrane as well as the well-aligned protein fibers within an axon restricts water diffusion perpendicular to the fiber orientation, leading to anisotropic water diffusion in brain WM 1. Myelin sheaths around the axons may also contribute to the anisotropy for both intra- and extracellular water 2.

The quantitative description of this anisotropy could be detect....

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Analysis Methods: Pre- and Postprocessing

The task of the following protocol is to analyze diffusion properties voxelwise within white matter tracts which could be - due to the voxelwise detection - either isotropic or anisotropic, resulting in prolate or oblate diffusion tensors for the respective voxels. The parameterization of the voxel tensors is used for either the calculation of FA-maps or the identification of fibertracts (Figure 1).

In order t.......

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1. QC and correction for corrupted gradient directions in application to data of patients with hyperkinetic disorders

As an example for the effect of the application of QC and subsequent volume exclusion (as a consequence from the correction for corrupted GD), Figure 8 shows differences in whole brain based spatial statistics with and without volume exclusion for group comparison of 29 premanifest Huntington's disease subjects vs. 30 age and gender matched controls. The scanning .......

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Inter-subject averaging of DTI data can be achieved with respect to diffusion amplitude (by use of FA information) and diffusion direction (based upon FT), respectively. Averaging of FA maps allows for the statistical comparison of subject groups by WBSS and TFAS. This methodological framework gives an introduction to DTI techniques with inter-subject averaging and group comparison. Stereotaxic normalization and comparison of FA maps at the group level allows for several possibilities to quantify differences between subj.......

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Parts of this work, i.e. the study on QC and correction for corrupted gradient directions in application to data of patients with hyperkinetic disorders, were supported by the European HD network (EHDN project 070). The MRI scans in this certain study were acquired as part of the London site TRACK-HD cohort.

....

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Name Company Catalog Number Comments
MR scanner Siemens 1.5 T Magnetom Symphony
analysis software TIFT - Tensor Imaging and Fiber Tracking

  1. Moseley, M. E., Cohen, Y., et al. Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology. 176, 439-445 (1990).
  2. Mori, S., van Zijl, P. C. M. Fiber tracking: principles and strategies - a technical review. NMR Biomed. 15, 468-480 (2002).
  3. Basser, P. J., Mattiello, J., LeBihan, D. MR Diffusion Tensor Spectroscopy and Imaging. Biophys J. 66, 259-267 (1994).
  4. Mattiello, J., Basser, J. P., Le Bihan, D. Analytical expression for the b-matrix in NMR diffusion imaging and spectroscopy. J. Magn. Reson. A. 108, 131-141 (1994).
  5. Pierpaoli, C., Basser, P. J. Toward a quantitative assessment of diffusion anisotropy. Magn. Reson. Med. 36, 893-906 (1996).
  6. Pajevic, S., Pierpaoli, C. Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain. Magn. Reson. Med. 42, 526-540 (1999).
  7. Le Bihan, D., Mangin, J. F., et al. Diffusion tensor imaging: concepts and applications. J. Magn. Reson. Imaging. 13, 534-546 (2001).
  8. Conturo, T. E., Lori, N. F., et al. Tracking neuronal fibre pathways in the living human brain. Proc. Natl. Acad. Sci. U.S.A. 96, 10422-10427 (1999).
  9. Lori, N. F., Akbudak, E. Diffusion tensor fibre tracking of human brain connectivity: aquisition methods, reliability analysis and biological results. NMR Biomed. 15, 494-515 (2002).
  10. Smith, S. M., Jenkinson, M., et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 31, 1487-1505 (2006).
  11. Agosta, F., Pagani, E., et al. Assessment of white matter tract damage in patients with amyotrophic lateral sclerosis: a diffusion tensor MR imaging tractography study. AJNR. Am. J. Neuroradiol. 31, 1457-1461 (2010).
  12. Talairach, J., Tournoux, P. . Coplanar stereotaxic atlas of the human brain. , (1988).
  13. Brett, M., Johnsrude, I. S., Owen, A. M. The problem of functional localization in the human brain. Nat. Rev. Neurosci. 3, 243-249 (2002).
  14. Collins, D. L., Neelin, P., Peters, T. M., Evans, A. C. Automatic 3-D intersubject registration of MR volumetric data in standardized Talairach space. J. Comput. Assist. Tomogr. 18, 192-205 (1994).
  15. Friston, K. J., Ashburner, J., Frith, C. D., Poline, J. -. B., Heather, J. D., Frackowiak, R. S. J. Spatial registration and normalization of images. Human Brain Mapp. 2, 165-189 (1995).
  16. Alexander, D. C., Pierpaoli, C., Basser, P. J., Gee, J. C. Spatial transformations of diffusion tensor magnetic resonance images. IEEE Trans. Med. Imaging. 20, 1131-1139 (2001).
  17. Müller, H. -. P., Unrath, A., Ludolph, A. C., Kassubek, J. Preservation of Diffusion Tensor Properties during Spatial Normalization by use of Tensor imaging and Fiber Tracking on a Normal Brain Database. Phys. Med. Biol. 52, N99-N109 (2007).
  18. Likitjaroen, Y., Meindl, T., et al. Longitudinal changes of fractional anisotropy in Alzheimer's disease patients treated with galantamine: a 12-month randomized, placebo-controlled, double-blinded study. Eur. Arch. Psychiatry Clin. Neurosci. 262, 341-350 (2012).
  19. Zhang, Y., Schuff, N. Progression of white matter degeneration in amyotrophic lateral sclerosis: A diffusion tensor imaging study. Amyotroph. Lateral Scler. 12, 421-429 (2011).
  20. Pierpaoli, C., Barnett, A. Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage. 13, 1174-1185 (2001).
  21. Agosta, F., Valsasina, P., et al. Sensorimotor functional connectivity changes in amyotrophic lateral sclerosis. Cereb Cortex. 21, 2291-2298 (2011).
  22. Müller, H. -. P., Unrath, A., Huppertz, H. J., Ludolph, A. C., Kassubek, J. Neuroanatomical patterns of cerebral white matter involvement in different motor neuron diseases as studied by diffusion tensor imaging analysis. Amyotroph Lateral Scler. 13, 254-264 (2012).
  23. Reich, D. S., Zackowski, K. M. Corticospinal tract abnormalities are associated with weakness in multiple sclerosis. Am. J. Neuroradiol. 29, 333-339 (2008).
  24. Abe, O., Yamada, H. Amyotrophic lateral sclerosis: Diffusion tensor tractography and voxel-based analysis. NMR Biomed. 17, 411-416 (2004).
  25. Sage, C. A., Peeters, R. R., Gorner, A., Robberecht, W., Sunaert, S. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage. 34, 486-499 (2007).
  26. Preti, M. G., Baglio, F., et al. Assessing corpus callosum changes in Alzheimer's disease: comparison between tract-based spatial statistics and atlas-based tractography. PLoS One. 7, e35856 (2012).
  27. Borroni, B., Brambati, S. M., et al. Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia. Arch. Neurol. 64, 246-251 (2007).
  28. Unrath, A., Müller, H. -. P., Riecker, A., Ludolph, A. C., Sperfeld, A. D., Kassubek, J. Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging. Hum Brain Mapp. 31, 1727-1740 (2010).
  29. Müller, H. -. P., Lulé, D., Unrath, A., Ludolph, A. C., Riecker, A., Kassubek, J. Complementary Image Analysis of Diffusion Tensor Imaging and 3-Dimensional T1-Weighted Imaging: White Matter Analysis in Amyotrophic Lateral Sclerosis. J. Neuroimaging. 21, 24-33 (2011).
  30. Müller, H. -. P., Unrath, A., Sperfeld, A. D., Ludolph, A. C., Riecker, A., Kassubek, J. Diffusion tensor imaging and tractwise fractional anisotropy statistics: quantitative analysis in white matter pathology. Biomed. Eng. Online. 6, 42 (2007).
  31. Müller, H. -. P., Unrath, A., Riecker, A., Pinkhardt, E. H., Ludolph, A. C., Kassubek, J. Inter-subject variability in the analysis of diffusion tensor imaging at the group level: fractional anisotropy mapping and fiber tracking techniques. Magn. Reson. Imaging. 27, 324-334 (2009).
  32. Müller, H. -. P., Glauche, V., et al. Stability of white matter changes related to Huntington's disease in the presence of imaging noise: a DTI study. PLoS Curr. 3, RRN1232 (2011).
  33. Müller, H. -. P., Süßmuth, S. D., Landwehrmeyer, G. B., Ludolph, A. C., Tabrizi, S. J., Klöppel, S., Kassubek, J. Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease. PLoS Curr. 3, RRN1292 (2011).
  34. Shen, Y., Larkman, D. J., Counsell, S., Pu, I. M., Edwards, D., Hajnal, J. V. Correction of High-Order Eddy Current Induced Geometric Distortion in Diffusion-Weighted Echo-Planar images. Magn. Reson. Med. 52, 1184-1189 (2004).
  35. Ashburner, J., Friston, K. J. Nonlinear Spatial Normalization Using Basis Functions. Human Brain Mapping. 7, 254-266 (1999).
  36. Jones, D. K., Symms, M. R., Cercignani, M., Howard, R. J. The effect of filter size on VBM analyses of DT-MRI data. Neuroimage. 26, 546-554 (2005).
  37. Kunimatsu, A., Aoki, S., et al. The optimal trackability threshold of fractional anisotropy for diffusion tensor tractography of the corticospinal tract. Magn. Reson. Med. Sci. 3, 11-17 (2004).
  38. Genovese, C. R., Lazar, N. A., Nichols, T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage. 15, 870-878 (2002).
  39. Cleaver, J. E. Defective repair replication of DNA in xeroderma pigmentosum. Nature. 218, 652-656 (1968).
  40. Anttinen, A., Koulu, L., et al. Neurological symptoms and natural course of xeroderma pigmentosum. Brain. 131, 1979-1989 (2008).
  41. Kassubek, J., Sperfeld, A. D. The cerebro-morphological fingerprint of a progeroid syndrome: white matter changes correlate with neurological symptoms in xeroderma pigmentosum. PLoS One. 7, e30926 (2012).
  42. Canu, E., Agosta, F. The topography of brain microstructural damage in amyotrophic lateral sclerosis assessed using diffusion tensor MR imaging. AJNR. Am. J. Neuroradiol. 32, 1307-1314 (2011).
  43. Verstraete, E., Veldink, J. H., Hendrikse, J., Schelhaas, H. J., van den Heuvel, M. P., van den Berg, L. H. Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry. 83, 383-388 (2012).
  44. Hofer, S., Frahm, J. Topography of the human corpus callosum revisited- comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage. 32, 989-994 (2006).
  45. Iwata, N. K., Kwan, J. Y., et al. White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis. Brain. 134, 2642-2655 (2011).
  46. Kassubek, J., Ludolph, A. C., Müller, H. -. P. Neuroimaging of motor neuron diseases. Ther. Adv. Neurol. Disord. 5, 119-127 (2012).
  47. Kassubek, J., Juengling, F. D. . Multimodality functional neuroimaging. In: C. Stippich (Ed.): Clinical functional MRI - Presurgical functional neuroimaging. , (2007).
  48. Stadlbauer, A., Buchfelder, M., Salomonowitz, E., Ganslandt, O. Fiber density mapping of gliomas: histopathologic evaluation of a diffusion-tensor imaging data processing method. Radiology. , 257-846 (2010).
  49. Stadlbauer, A., Hammen, T., et al. Differences in metabolism of fiber tract alterations in gliomas: a combined fiber density mapping and magnetic resonance spectroscopic imaging study. Neurosurgery. 71, 454-463 (2012).
  50. Staempfli, P., Jaermann, T., Crelier, G. R., Kollias, S., Valavanis, A., Boesiger, P. Resolving fiber crossing using advanced fast marching tractography based on diffusion tensor imaging. Neuroimage. 30, 110-120 (2006).
  51. Ehricke, H. H., Otto, K. M., Klose, U. Regularization of bending and crossing white matter fibers in MRI Q-ball fields Magn. Reson Imaging. 29, 916-926 (2011).
  52. Hirsch, J. G., Schwenk, S. M., Rossmanith, C., Hennerici, M. G., Gass, A. Deviations from the diffusion tensor model as revealed by contour plot visualization using high angular resolution diffusion-weighted imaging (HARDI). MAGMA. 16, 93-102 (2003).
  53. Lazar, M., Weinstein, D. M., et al. White matter tractography using diffusion tensor deflection. Human Brain Mapping. 18, 306-321 (2003).
  54. Reisert, M., Mader, I., Anastasopoulos, C., Weigel, M., Schnell, S., Kiselev, V. Global fiber reconstruction becomes practical. Neuroimage. 54, 955-962 (2011).
  55. Klein, A., Andersson, J. Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. Neuroimage. 46, 786-802 (2009).
  56. Bammer, R. Basic principles of diffusion-weighted imaging. Eur. J. Radiol. 45, 169-184 (2003).
  57. Mohammadi, S., Keller, S. S. The influence of spatial registration on detection of cerebral asymmetries using voxel-based statistics of fractional anisotropy images and TBSS. PLoS One. 7, e36851 (2012).
  58. Turner, M. R., Grosskreutz, , et al. Towards a neuroimaging biomarker for amyotrophic lateral sclerosis. Lancet Neurol. 10, 400-403 (2011).
  59. Müller, H. -. P., Kassubek, J., Enderle, J. D. Multimodal imaging in neurology - special focus on MRI applications and MEG. Synthesis Lectures in Biomedical Engineering. 16, (2008).
  60. Douaud, G., Filippini, N., Knight, S., Talbot, K., Turner, M. R. Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. Brain. 134, 3470-3479 (2011).
  61. Kolind, S. H., Laule, C., et al. Complementary information from multi-exponential T2 relaxation and diffusion tensor imaging reveals differences between multiple sclerosis lesions. Neuroimage. 40, 77-85 (2008).
  62. Verma, R., Zacharaki, E. I. Multiparametric tissue characterization of brain neoplasms and their recurrence using pattern classification of MR images. Acad. Radiol. 15, 966-977 (2008).

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