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European Radiology

, 18:2691 | Cite as

Voxel-based morphometry and diffusion-tensor MR imaging of the brain in long-term survivors of childhood leukemia

  • L. PortoEmail author
  • C. Preibisch
  • E. Hattingen
  • M. Bartels
  • T. Lehrnbecher
  • R. Dewitz
  • F. Zanella
  • C. Good
  • H. Lanfermann
  • R. DuMesnil
  • M. Kieslich
Oncology

Abstract

The aims of this study were to detect morphological changes in neuroanatomical components in adult survivors of acute lymphoblastic leukemia (ALL). Voxel-based morphometry (VBM) can be used to detect subtle structural changes in brain morphology and via analysis of fractional anisotropy (FA), diffusion-tensor imaging (DTI) can non-invasively probe white matter (WM) integrity. We used VBM and DTI to examine 20 long-term survivors of ALL and 21 healthy matched controls. Ten ALL survivors received chemotherapy and irradiation; ten survivors received chemotherapy alone during childhood. Imaging was performed on a 3.0-T MRI. For VBM, group comparisons of segmented T1-weighted grey matter (GM) and WM images from controls and ALL survivors were performed separately for patients who received chemotherapy alone and who received chemotherapy and irradiation. For DTI, FA in WM was compared for the same groups. Survivors of childhood ALL who underwent cranial irradiation during childhood had smaller WM volumes and reduced GM concentration within the caudate nucleus and thalamus. The FA in WM was reduced in adult survivors of ALL but the effect was more severe after combined treatment with irradiation and chemotherapy. Our results indicate that DTI and VBM can reveal persistent long-term WM and caudate changes in children after ALL treatment, even without T2 changes in conventional imaging.

Keywords

Children Leukemia Central nervous system MRI Morphometry Diffusion images 

References

  1. 1.
    Precourt S, Robaey P, Lamothe I, Lassonde M, Sauerwein HC, Moghrabi A (2002) Verbal cognitive functioning and learning in girls treated for acute lymphoblastic leukemia by chemotherapy with or without cranial irradiation. Dev Neuropsychol 21:173–195PubMedCrossRefGoogle Scholar
  2. 2.
    Langer T, Martus P, Ottensmeier H, Hertzberg H, Beck JD, Meier W (2002) CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL: impairments of concentration, attention, and memory. Med Pediatr Oncol 38:320–328PubMedCrossRefGoogle Scholar
  3. 3.
    von der Weid N, Swiss Pediatric Oncology Group (SPOG) (2001) Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study. Swiss Med Wkly 131:180–187Google Scholar
  4. 4.
    Good CD, Johnsrude I, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14:685–700PubMedCrossRefGoogle Scholar
  5. 5.
    Le Bihan D, Mangin JF, Poupon C et al (2001) Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 13:534–546PubMedCrossRefGoogle Scholar
  6. 6.
    Neil J, Miller J, Mukherjee P et al (2002) Diffusion tensor imaging of normal and injured developing human brain—a technical review. NMR Biomed 15:543–552PubMedCrossRefGoogle Scholar
  7. 7.
    Suzuki Y, Matsuzawa H, Kwee IL et al (2003) Absolute value diffusion tensor analysis for human brain maturation. NMR Biomed 16:257–260PubMedCrossRefGoogle Scholar
  8. 8.
    Barnea-Goraly N, Menon V, Eckert M et al (2005) White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb Cortex 15:1848–1854PubMedCrossRefGoogle Scholar
  9. 9.
    Snook L, Paulson LA, Roy D et al (2005) Diffusion tensor imaging of neurodevelopment in children and young adults. Neuroimage 26:1164–1173PubMedCrossRefGoogle Scholar
  10. 10.
    Hermoye L, Saint-Martin C, Cosnard G et al (2006) Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood. Neuroimage 29:493–504PubMedCrossRefGoogle Scholar
  11. 11.
    Deichmann R, Schwarzbauer C, Turner R (2003) Optimisation of the 3D MDEFT sequence for anatomical brain imaging: technical implications at 1.5 and 3 T. Neuroimage 21:757–767CrossRefGoogle Scholar
  12. 12.
    Ashburner J, Friston KJ (2000) Voxel-based morphometry-the methods. Neuroimage 11:805–821PubMedCrossRefGoogle Scholar
  13. 13.
    Ashburner J, Friston KJ (2001) Why voxel-based morphometry should be used. Neuroimage 14:1238–1243PubMedCrossRefGoogle Scholar
  14. 14.
    Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289PubMedCrossRefGoogle Scholar
  15. 15.
    Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain: a 3-dimensional proportional system, an approach to cerebral imaging. Thieme, New YorkGoogle Scholar
  16. 16.
    Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas CS, Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT (2000) Automated Talairach atlas labels for functional brain mapping. Human Brain Mapping 10:120–131PubMedCrossRefGoogle Scholar
  17. 17.
    Jezzard P Balaban RS (1995) Correction for geometric distortion in echo planar images from B0 field variations. Magn Reson Med 34:65–73CrossRefGoogle Scholar
  18. 18.
    Cusack R, Brett M, Osswald K (2003) An evaluation of the use of magnetic field maps to undistort echo-planar images. Neuroimage 18:127–142PubMedCrossRefGoogle Scholar
  19. 19.
    Basser PJ, Mattiello J, LeBihan D (1994) Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 103(3):247–254PubMedCrossRefGoogle Scholar
  20. 20.
    Evans AC, Collins DL, Mills SR, Brown ED, Kelly RL, Peters TM (1993) 3D statistical neuroanatomical models from 305 MRI volumes. Proc IEEE Nucl Sci Symp Med Imaging Conf, MTP Press, London, pp 1813–1817Google Scholar
  21. 21.
    Reddick WE, White H, Glass JO et al (2003) Developmental model relating white matter volume with neurocognitive deficits in pediatric brain tumor survivors. Cancer 97:2512–2519PubMedCrossRefGoogle Scholar
  22. 22.
    Reddick WE, Glass JO, Palmer SL et al (2005) Atypical white matter volume development in children following craniospinal irradiation. Neuro Oncol 7:12–19PubMedCrossRefGoogle Scholar
  23. 23.
    Reddick WE, Glass JO, Helton KJ, Langston JW, Xiong X, Pui C-H (2005) Leukoencephalopathy prevalence in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 2615:1263–1269Google Scholar
  24. 24.
    Reddick WE, Glass JO, Helton KJ, Langston JW, Chin-Shang L, Pui C-H (2005) A quantitative MRI assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation. AJNR Am J Neuroradiol 26:2371–2377PubMedGoogle Scholar
  25. 25.
    Paakko E, Harila-Saari A, Vanionpaa L, Himanen S, Pyhtinen J, Lanning M (2000) White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings. Med Pediatr Oncol 35:456–461PubMedCrossRefGoogle Scholar
  26. 26.
    Chu WCW, Chik KW, Chan YL et al (2003) White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy 1. Radiology 229:659–669PubMedCrossRefGoogle Scholar
  27. 27.
    Espy KA, Moore IMK, Kaufmann PM, Kramer JH, Matthay K, Hutter JJ (2001) Chemotherapeutic CNS prophylaxis and neuropsychologic change in children with acute lymphoblastic leukemia: a prospective study. J Pediatr Psychol 26:1–9PubMedCrossRefGoogle Scholar
  28. 28.
    Reddick WE, Shan ZY, Glass JO, Helton S, Xiong X, Wu S, Bonner MJ, Howard SC, Christensen R, Khan RB, Pui CH, Mulhern RK (2006) Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer 106:941–949PubMedCrossRefGoogle Scholar
  29. 29.
    Alexander GE, Delong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–358PubMedCrossRefGoogle Scholar
  30. 30.
    Ochs JJ (1989) Neurotoxicity due to central nervous system therapy for childhood leukemia. Am J Pediatr Hematol Oncol 11:93–105PubMedCrossRefGoogle Scholar
  31. 31.
    Mennes M, Stiers P, Vandenbussche E et al (2005) Attention and information processing in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Pediatr Blood Cancer 44:479–486CrossRefGoogle Scholar
  32. 32.
    Rodgers J, Marckus R, Kearns P, Windebank K (2003) Attentional ability among survivors of leukaemia treated without cranial irradiation. Arch Dis Child 88:147–150PubMedCrossRefGoogle Scholar
  33. 33.
    Montour-Proulx I, Kuehn SM, Keene DL et al (2005) Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the Pediatric Oncology Group 9605 Protocol. J Child Neurol 20:129–133PubMedCrossRefGoogle Scholar
  34. 34.
    Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17:83–93PubMedCrossRefGoogle Scholar
  35. 35.
    Vymazal J, Brooks RA, Baumgarner C (1996) The relation between brain iron and NMR relaxation times: an in vitro study. Magn Reson Med 35:56–61PubMedCrossRefGoogle Scholar
  36. 36.
    Smith B (1975) Brain damage after intrathecal methotrexate. J Neurol Neurosurg Psychiatr 38:810–815PubMedCrossRefGoogle Scholar
  37. 37.
    Emsley JG, Mitchell BD, Kempermann G, Macklis JD (2005) Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog Neurobiol 75:321–341PubMedCrossRefGoogle Scholar
  38. 38.
    Magavi SS, Mitchell BD, Szentirmai O, Carter BS, Macklis JD (2005) Adult-born and preexisting olfactory granule neurons undergo distinct experience-dependent modifications of their olfactory responses in vivo. J Neurosci 25:10729–10739PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2008

Authors and Affiliations

  • L. Porto
    • 1
    Email author
  • C. Preibisch
    • 2
  • E. Hattingen
    • 1
  • M. Bartels
    • 3
  • T. Lehrnbecher
    • 4
  • R. Dewitz
    • 4
  • F. Zanella
    • 1
  • C. Good
    • 5
  • H. Lanfermann
    • 6
  • R. DuMesnil
    • 1
  • M. Kieslich
    • 3
  1. 1.Department of NeuroradiologyKlinikum Goethe UniversitätFrankfurtGermany
  2. 2.Brain Imaging CenterJohann Wolfgang Goethe UniversitätFrankfurtGermany
  3. 3.NeuropediatricsJohann Wolfgang Goethe UniversitätFrankfurtGermany
  4. 4.Pediatric Hematology/OncologyJohann Wolfgang Goethe UniversitätFrankfurtGermany
  5. 5.Brighton Sussex HospitalsBrightonUK
  6. 6.NeuroradiologyHannover Medical SchoolHannoverGermany

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