Brain Structure and Function

, Volume 219, Issue 5, pp 1627–1638 | Cite as

White matter organization in relation to upper limb motor control in healthy subjects: exploring the added value of diffusion kurtosis imaging

  • J. GooijersEmail author
  • A. Leemans
  • S. Van Cauter
  • S. Sunaert
  • S. P. Swinnen
  • K. Caeyenberghs
Original Article


Diffusion tensor imaging (DTI) characterizes white matter (WM) microstructure. In many brain regions, however, the assumption that the diffusion probability distribution is Gaussian may be invalid, even at low b values. Recently, diffusion kurtosis imaging (DKI) was suggested to more accurately estimate this distribution. We explored the added value of DKI in studying the relation between WM microstructure and upper limb coordination in healthy controls (N = 24). Performance on a complex bimanual tracking task was studied with respect to the conventional DTI measures (DKI or DTI derived) and kurtosis metrics of WM tracts/regions carrying efferent (motor) output from the brain, corpus callosum (CC) substructures and whole brain WM. For both estimation models, motor performance was associated with fractional anisotropy (FA) of the CC-genu, CC-body, the anterior limb of the internal capsule, and whole brain WM (r s range 0.42–0.63). Although DKI revealed higher mean, radial and axial diffusivity and lower FA than DTI (p < 0.001), the correlation coefficients were comparable. Finally, better motor performance was associated with increased mean and radial kurtosis and kurtosis anisotropy (r s range 0.43–0.55). In conclusion, DKI provided additional information, but did not show increased sensitivity to detect relations between WM microstructure and bimanual performance in healthy controls.


Bimanual motor control Diffusion tensor imaging Excess kurtosis Non-Gaussian diffusion 



This work was supported by a grant from the Research Programme of the Research Foundation—Flanders (Fonds Wetenschappelijk Onderzoek—FWO) (G.0482.010, G0483.10, G.A114.11, G0721.12), from the Research Fund of the Katholieke Universiteit Leuven, Belgium (OT/11/071), and Grant P7/11 from the Interuniversity Attraction Poles program of the Belgian federal government, awarded to S.P. Swinnen. J. Gooijers is funded by an aspirant fellowship of the Research Foundation—Flanders (FWO).

Conflict of interest

There are no conflicts of interest.

Supplementary material

429_2013_590_MOESM1_ESM.pdf (355 kb)
Supplementary material 1 (PDF 355 kb)
429_2013_590_MOESM2_ESM.pdf (345 kb)
Supplementary material 2 (PDF 344 kb)


  1. Basser PJ, Jones DK (2002) Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review. NMR Biomed 15:456–467PubMedCrossRefGoogle Scholar
  2. Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219PubMedCrossRefGoogle Scholar
  3. Basser PJ, Mattiello J, Lebihan D (1994) MR Diffusion tensor spectroscopy and imaging. Biophys J 66:259–267PubMedCentralPubMedCrossRefGoogle Scholar
  4. Bleyenheuft Y, Grandin CB, Cosnard G, Olivier E, Thonnard JL (2007) Corticospinal dysgenesis and upper-limb deficits in congenital hemiplegia: a diffusion tensor imaging study. Pediatrics 120:E1502–E1511PubMedCrossRefGoogle Scholar
  5. Bonzano L, Tacchino A, Roccatagliata L, Abbruzzese G, Mancardi GL, Bove M (2008) Callosal contributions to simultaneous bimanual finger movements. J Neurosci 28:3227–3233PubMedCrossRefGoogle Scholar
  6. Caeyenberghs K, Leemans A, Geurts M, Taymans T, Vander Linden C, Smits-Engelsman BCM, Sunaert S, Swinnen SP (2010a) Brain-behavior relationships in young traumatic brain injury patients: DTI metrics are highly correlated with postural control. Hum Brain Mapp 31:992–1002PubMedCrossRefGoogle Scholar
  7. Caeyenberghs K, Leemans A, Geurts M, Taymans T, Vander Linden C, Smits-Engelsman BCM, Sunaert S, Swinnen SP (2010b) Brain-behavior relationships in young traumatic brain injury patients: fractional anisotropy measures are highly correlated with dynamic visuomotor tracking performance. Neuropsychologia 48:1472–1482PubMedCrossRefGoogle Scholar
  8. Caeyenberghs K, Leemans A, Geurts M, Vander Linden C, Smits-Engelsman BCM, Sunaert S, Swinnen SP (2011) Correlations between white matter integrity and motor function in traumatic brain injury patients. Neurorehabil Neural Repair 25:492–502PubMedCrossRefGoogle Scholar
  9. Callaghan PT (1991) Principles of nuclear magnetic resonance microscopy. Oxford University Press, OxfordGoogle Scholar
  10. Cheung MM, Hui ES, Chan KC, Helpern JA, Qi LQ, Wu EX (2009) Does diffusion kurtosis imaging lead to better neural tissue characterization? A rodent brain maturation study. Neuroimage 45:386–392PubMedCrossRefGoogle Scholar
  11. Clark CA, Le Bihan D (2000) Water diffusion compartmentation and anisotropy at high b values in the human brain. Magn Reson Med 44:852–859PubMedCrossRefGoogle Scholar
  12. Dell’Acqua F, Scifo P, Rizzo G, Catani M, Simmons A, Scotti G, Fazio F (2010) A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution. Neuroimage 49:1446–1458PubMedCrossRefGoogle Scholar
  13. Falangola MF, Jensen JH, Babb JS, Hu C, Castellanos FX, Di Martino A, Ferris SH, Helpern JA (2008) Age-related non-gaussian diffusion patterns in the prefrontal brain. J Magn Reson Imaging 28:1345–1350PubMedCentralPubMedCrossRefGoogle Scholar
  14. Falangola MF, Jensen JH, Tabesh A, Hu C, Deardorff RL, Babb JS, Ferris S, Helpern JA (2013) Non-Gaussian diffusion MR assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease. Magn Reson Imaging 31:840–846Google Scholar
  15. Fieremans E, De Deene Y, Delputte S, Ozdemir MS, D’Asseler Y, Vlassenbroeck J, Deblaere K, Achten E, Lemahieu I (2008) Simulation and experimental verification of the diffusion in an anisotropic fiber phantom. J Magn Reson 190:189–199PubMedCrossRefGoogle Scholar
  16. Fieremans E, Jensen JH, Helpern JA (2011) White matter characterization with diffusional kurtosis imaging. Neuroimage 58:177–188PubMedCentralPubMedCrossRefGoogle Scholar
  17. Fling BW, Walsh CM, Bangert AS, Reuter-Lorenz PA, Welsh RC, Seidler RD (2011) Differential callosal contributions to bimanual control in young and older adults. J Cogn Neurosci 23:2171–2185PubMedCrossRefGoogle Scholar
  18. Gooijers J, Caeyenberghs K, Sisti HM, Geurts M, Heitger MH, Leemans A, Swinnen SP (2013) Diffusion tensor imaging metrics of the corpus callosum in relation to bimanual coordination: effect of task complexity and sensory feedback. Hum Brain Mapp 34:241–252PubMedCrossRefGoogle Scholar
  19. Grossman EJ, Ge YL, Jensen JH, Babb JS, Miles L, Reaume J, Silver JM, Grossman RI, Inglese M (2012) Thalamus and cognitive impairment in mild traumatic brain injury: a diffusional kurtosis imaging study. J Neurotrauma 29:2318–2327Google Scholar
  20. Helpern JA, Adisetiyo V, Falangola MF, Hu CX, Di Martino A, Williams K, Castellanos FX, Jensen JH (2011) Preliminary evidence of altered gray and white matter microstructural development in the frontal lobe of adolescents with attention-deficit hyperactivity disorder: a diffusional kurtosis imaging study. J Magn Reson Imaging 33:17–23PubMedCentralPubMedCrossRefGoogle Scholar
  21. Hui ES, Cheung MM, Qi LQ, Wu EX (2008) Towards better MR characterization of neural tissues using directional diffusion kurtosis analysis. Neuroimage 42:122–134PubMedCrossRefGoogle Scholar
  22. Jansen JFA, Stambuk HE, Koutcher JA, Shukla-Dave A (2010) Non-Gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: a feasibility study. AJNR 31:741–748PubMedCentralPubMedCrossRefGoogle Scholar
  23. Jensen JH, Helpern JA (2010) MRI quantification of non-Gaussian water diffusion by kurtosis analysis. NMR Biomed 23:698–710PubMedCentralPubMedCrossRefGoogle Scholar
  24. Jensen JH, Helpern JA, Ramani A, Lu HZ, Kaczynski K (2005) Diffusional kurtosis imaging: the quantification of non-Gaussian water diffusion by means of magnetic resonance imaging. Magn Reson Med 53:1432–1440PubMedCrossRefGoogle Scholar
  25. Jensen JH, Falangola MF, Hu CX, Tabesh A, Rapalino O, Lo C, Helpern JA (2011) Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction. NMR Biomed 24:452–457PubMedCentralPubMedCrossRefGoogle Scholar
  26. Jeurissen B, Leemans A, Tournier JD, Jones DK, Sijbers J (2012) Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp. doi: 10.1002/hbm.22099
  27. Johansen-Berg H, Della-Maggiore V, Behrens TEJ, Smith SM, Paus T (2007) Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills. Neuroimage 36:T16–T21PubMedCentralPubMedCrossRefGoogle Scholar
  28. Jones DK, Basser PJ (2004) “Squashing peanuts and smashing pumpkins”: how noise distorts diffusion-weighted MR data. Magn Reson Med 52:979–993PubMedCrossRefGoogle Scholar
  29. Jones DK, Leemans A (2011) Diffusion tensor imaging. Methods Mol Biol 711:127–144PubMedCrossRefGoogle Scholar
  30. Kärger J (1985) Nmr self-diffusion studies in heterogeneous systems. Adv Colloid Interface Sci 23:129–148CrossRefGoogle Scholar
  31. Kiselev VG, Il’yasov KA (2007) Is the “biexponential diffusion” bilexponential? Magn Reson Med 57:464–469PubMedCrossRefGoogle Scholar
  32. Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas ES, Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT (2000) Automated Talairach Atlas labels for functional brain mapping. Hum Brain Mapp 10:120–131PubMedCrossRefGoogle Scholar
  33. Lancaster JL, Tordesillas-Gutierrez D, Martinez M, Salinas F, Evans A, Zilles K, Mazziotta JC, Fox PT (2007) Bias between MNI and talairach coordinates analyzed using the ICBM-152 brain template. Hum Brain Mapp 28:1194–1205PubMedCrossRefGoogle Scholar
  34. Lazar M, Jensen JH, Xuan L, Helpern JA (2008) Estimation of the orientation distribution function from diffusional kurtosis imaging. Magn Reson Med 60:774–781PubMedCentralPubMedCrossRefGoogle Scholar
  35. Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, Chabriat H (2001) Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 13:534–546PubMedCrossRefGoogle Scholar
  36. Leemans A, Jones DK (2009) The B-matrix must be rotated when correcting for subject motion in DTI data. Magn Reson Med 61:1336–1349PubMedCrossRefGoogle Scholar
  37. Leemans A et al (2009) ExploreDTI: A graphical toolbox for processing, analyzing, and visualizing diffusion MR data. In: 17th annual meeting of Intl Soc Mag Reson Med, p 3537. Hawaii, USAGoogle Scholar
  38. Liu CL, Bammer R, Acar B, Moseley ME (2004) Characterizing non-Gaussian diffusion by using generalized diffusion tensors. Magn Reson Med 51:924–937PubMedCrossRefGoogle Scholar
  39. Lu HZ, Jensen JH, Ramani A, Helpern JA (2006) Three-dimensional characterization of non-Gaussian water diffusion in humans using diffusion kurtosis imaging. NMR Biomed 19:236–247PubMedCrossRefGoogle Scholar
  40. Maier SE, Mulkern RV (2008) Biexponential analysis of diffusion-related signal decay in normal human cortical and deep gray matter. Magn Reson Imaging 26:897–904PubMedCentralPubMedCrossRefGoogle Scholar
  41. Maier SE, Vajapeyam S, Mamata H, Westin CF, Jolesz FA, Mulkern RV (2004) Biexponential diffusion tensor analysis of human brain diffusion data. Magn Reson Med 51:321–330PubMedCrossRefGoogle Scholar
  42. Minati L, Aquino D, Rampoldi S, Papa S, Grisoli M, Bruzzone MG, Maccagnano E (2007) Biexponential and diffusional kurtosis imaging, and generalised diffusion-tensor imaging (GDTI) with rank-4 tensors: a study in a group of healthy subjects. Magn Reson Mater Phy 20:241–253CrossRefGoogle Scholar
  43. Mori S, Wakana S, Van Zijl PCM, Nagae-Poetscher LM (2005) MRI atlas of the human white matter. Elsevier, AmsterdamGoogle Scholar
  44. Muetzel RL, Collins PF, Mueller BA, Schissel AM, Lim KO, Luciana M (2008) The development of corpus callosum microstructure and associations with bimanual task performance in healthy adolescents. Neuroimage 39:1918–1925PubMedCentralPubMedCrossRefGoogle Scholar
  45. Mulkern RV, Haker SJ, Maier SE (2009) On high b diffusion imaging in the human brain: ruminations and experimental insights. Magn Reson Imaging 27:1151–1162PubMedCentralPubMedCrossRefGoogle Scholar
  46. Niendorf T, Dijkhuizen RM, Norris DG, Campagne MV, Nicolay K (1996) Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion-weighted imaging. Magn Reson Med 36:847–857PubMedCrossRefGoogle Scholar
  47. Oldfield RC (1971) Assessment and analysis of handedness—Edinburgh inventory. Neuropsychologia 9:97–113PubMedCrossRefGoogle Scholar
  48. Pfefferbaum A, Rosenbloom MJ, Adalsteinsson E, Sullivan EV (2007) Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain 130:48–64PubMedCrossRefGoogle Scholar
  49. Poot DHJ, den Dekker AJ, Achten E, Verhoye M, Sijbers J (2010) Optimal experimental design for diffusion kurtosis imaging. IEEE Trans Med Imaging 29:819–829PubMedCrossRefGoogle Scholar
  50. Preilowski B (1972) Possible contribution of anterior forebrain commissures to bilateral motor coordination. Neuropsychologia 10:267–277PubMedCrossRefGoogle Scholar
  51. Qiu MG, Darling WG, Morecraft RJ, Ni CC, Rajendra J, Butler AJ (2011) White matter integrity is a stronger predictor of motor function than BOLD response in patients with stroke. Neurorehabil Neural Repair 25:275–284PubMedCentralPubMedCrossRefGoogle Scholar
  52. Raab P, Hattingen E, Franz K, Zanella FE, Lanfermann H (2010) Cerebral gliomas: diffusional kurtosis imaging analysis of microstructural differences. Radiology 254:876–881PubMedCrossRefGoogle Scholar
  53. Raz E, Bester M, Sigmund EE, Tabesh A, Babb JS, Jaggi H, Helpern J, Mitnick RJ, Inglese M (2013) A better characterization of spinal cord damage in multiple sclerosis: a diffusional kurtosis imaging study. Am J Neuroradiol. doi: 10.3174/ajnr.A3512
  54. Rosenkrantz AB, Sigmund EE, Johnson G, Babb JS, Mussi TC, Melamed J, Taneja SS, Lee VS, Jensen JH (2012) Prostate cancer: feasibility and preliminary experience of a diffusional kurtosis model for detection and assessment of aggressiveness of peripheral zone cancer. Radiology 264:126–135PubMedCrossRefGoogle Scholar
  55. Schaechter JD, Fricker ZP, Perdue KL, Helmer KG, Vangel MG, Greve DN, Makris N (2009) Microstructural status of ipsilesional and contralesional corticospinal tract correlates with motor skill in chronic stroke patients. Hum Brain Mapp 30:3461–3474PubMedCentralPubMedCrossRefGoogle Scholar
  56. Schulte T, Sullivan EV, Muller-Oehring EM, Adalsteinsson E, Pfefferbaum A (2005) Corpus callosal microstructural integrity influences interhemispheric processing: a diffusion tensor imaging study. Cereb Cortex 15:1384–1392PubMedCrossRefGoogle Scholar
  57. Serrien DJ, Nirkko AC, Wiesendanger M (2001) Role of the corpus callosum in bimanual coordination: a comparison of patients with congenital and acquired callosal damage. Eur J Neurosci 14:1897–1905PubMedCrossRefGoogle Scholar
  58. Shelton FDAP, Reding MJ (2001) Effect of lesion location on upper limb motor recovery after stroke. Stroke 32:107–112PubMedCrossRefGoogle Scholar
  59. Sisti HM, Geurts M, Clerckx R, Gooijers J, Coxon JP, Heitger MH, Caeyenberghs K, Beets IAM, Serbruyns L, Swinnen SP (2011) Testing multiple coordination constraints with a novel bimanual visuomotor task. Plos One 6:e23619Google Scholar
  60. Sisti HM, Geurts M, Gooijers J, Heitger MH, Caeyenberghs K, Beets IAM, Serbruyns L, Leemans A, Swinnen SP (2012) Microstructural organization of corpus callosum projections to prefrontal cortex predicts bimanual motor learning. Learn Mem 19:351–357PubMedCrossRefGoogle Scholar
  61. Song F, Zhang F, Yin DZ, Hu YS, Fan MX, Ni HH, Nan XL, Cui X, Zhou CX, Huang CS, Zhao Q, Ma LH, Xu YM, Xia QJ (2012) Diffusion tensor imaging for predicting hand motor outcome in chronic stroke patients. J Int Med Res 40:126–133PubMedCrossRefGoogle Scholar
  62. Steiger JH (1980) Tests for comparing elements of a correlation matrix. Psychol Bull 87:245–251CrossRefGoogle Scholar
  63. Sullivan EV, Adalsteinsson E, Hedehus M, Ju C, Moseley M, Lim KO, Pfefferbaum A (2001) Equivalent disruption of regional white matter microstructure in ageing healthy men and women. NeuroReport 12:99–104PubMedCrossRefGoogle Scholar
  64. Szczepankiewicz F, Latt J, Wirestam R, Leemans A, Sundgren P, Van Westen D, Stahlberg F, Nilsson M (2013) Variability in diffusion kurtosis imaging: impact on study design, statistical power and interpretation. Neuroimage 76:145–154PubMedCrossRefGoogle Scholar
  65. Tournier JD, Calamante F, Connelly A (2007) Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. Neuroimage 35:1459–1472PubMedCrossRefGoogle Scholar
  66. Tournier JD, Mori S, Leemans A (2011) Diffusion tensor imaging and beyond. Magn Reson Med 65:1532–1556PubMedCentralPubMedCrossRefGoogle Scholar
  67. Trampel R, Jensen JH, Lee RF, Kamenetskiy I, McGuinness G, Johnson G (2006) Diffusional kurtosis imaging in the lung using hyperpolarized 3He. Magn Reson Med 56:733–737PubMedCrossRefGoogle Scholar
  68. Van Cauter S, Veraart J, Sijbers J, Peeters RR, Himmelreich U, De Keyzer F, Van Gool SW, Van Calenbergh F, De Vleeschouwer S, Van Hecke W, Sunaert S (2012) Gliomas: diffusion kurtosis mr imaging in grading. Radiology 263:492–501PubMedCrossRefGoogle Scholar
  69. Vanhoutte G, Pereson S, Delgado y Palacios R, Guns P, Asselbergh B, Veraart J, Sijbers J, Verhoye M, Van Broeckhoven C, Van der Linden A (2013) Diffusion kurtosis imaging to detect amyloidosis in an APP/PS1 mouse model for Alzheimer’s Disease. Magn Reson Med 69:1115–1121Google Scholar
  70. Veraart J, Poot DHJ, Van Hecke W, Blockx I, Van der Linden A, Verhoye M, Sijbers J (2011) More accurate estimation of diffusion tensor parameters using diffusion kurtosis imaging. Magn Reson Med 65:138–145PubMedCrossRefGoogle Scholar
  71. Veraart J, Rajan J, Peeters RR, Leemans A, Sunaert S, Sijbers J (2012) Comprehensive framework for accurate diffusion MRI parameter estimation. Magn Reson Med. doi: 10.1002/mrm.24529
  72. Vos SB, Jones DK, Jeurissen B, Viergever MA, Leemans A (2012) The influence of complex white matter architecture on the mean diffusivity in diffusion tensor MRI of the human brain. Neuroimage 59:2208–2216PubMedCrossRefGoogle Scholar
  73. Wang JJ, Lin WY, Lu CS, Weng YH, Ng SH, Wang CH, Liu HL, Hsieh RH, Wan YL, Wai YY (2011) Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology 261:210–217PubMedCrossRefGoogle Scholar
  74. Wedeen VJ, Hagmann P, Tseng WYI, Reese TG, Weisskoff RM (2005) Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging. Magn Reson Med 54:1377–1386PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • J. Gooijers
    • 1
    Email author
  • A. Leemans
    • 2
  • S. Van Cauter
    • 3
  • S. Sunaert
    • 3
  • S. P. Swinnen
    • 1
  • K. Caeyenberghs
    • 4
    • 1
  1. 1.Motor Control and Neuroplasticity Research Group, Department of Kinesiology, Group Biomedical SciencesKU LeuvenHeverleeBelgium
  2. 2.Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Department of RadiologyUniversity Hospital, KU LeuvenLeuvenBelgium
  4. 4.Department of Physical Therapy and Motor Rehabilitation, Faculty of Medicine and Health SciencesUniversity of GhentGhentBelgium

Personalised recommendations