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Neuroradiology

, Volume 53, Issue 2, pp 141–148 | Cite as

Proton MR spectroscopic imaging of basal ganglia and thalamus in neurofibromatosis type 1: correlation with T2 hyperintensities

  • Charlotte Barbier
  • Camille Chabernaud
  • Laurent Barantin
  • Philippe Bertrand
  • Catherine Sembely
  • Dominique Sirinelli
  • Pierre CastelnauEmail author
  • Jean-Philippe Cottier
Paediatric Neuroradiology

Abstract

Introduction

Neurofibromatosis type 1 (NF1) is frequently associated with hyperintense lesions on T2-weighted images called “unidentified bright objects” (UBO). To better characterize the functional significance of UBO, we investigate the basal ganglia and thalamus using spectroscopic imaging in children with NF1 and compare the results to anomalies observed on T2-weighted images.

Methods

Magnetic resonance (MR) data of 25 children with NF1 were analyzed. On the basis of T2-weighted images analysis, two groups were identified: one with normal MR imaging (UBO− group; n = 10) and one with UBO (UBO+ group; n = 15). Within the UBO+ group, a subpopulation of patients (n = 5) only had lesions of the basal ganglia. We analyzed herein seven regions of interest (ROIs) for each side: caudate nucleus, capsulo-lenticular region, lateral and posterior thalamus, thalamus (lateral and posterior voxels combined), putamen, and striatum. For each ROI, a spectrum of the metabolites and their ratio was obtained.

Results

Patients with abnormalities on T2-weighted images had significantly lower NAA/Cr, NAA/Cho, and NAA/mI ratios in the lateral right thalamus compared with patients with normal T2. These abnormal spectroscopic findings were not observed in capsulo-lenticular regions that had UBO but in the thalamus region that was devoid of UBO.

Conclusion

Multivoxel spectroscopic imaging using short-time echo showed spectroscopic abnormalities in the right thalamus of NF1 patients harboring UBO, which were mainly located in the basal ganglia. This finding could reflect the anatomical and functional interactions of these regions.

Keywords

Neurofibromatosis MRI Spectroscopy Basal ganglia Thalamus 

Notes

Acknowledgments

The authors thank the CIC INSERM 202, Tours, 37000, France, which is responsible for the study monitoring. The authors are grateful to Marc Sitbon and Devika Jutagir (USA) for careful reading and correction of the manuscript. This work was supported by the PHRC grant from the Region Centre and CHU de Tours & a fellowship of the Association Neurofibromatoses et Recklinghausen (ANR), France, to C. Chabernaud.

Conflict of interest

We declare that we have no conflict of interest.

References

  1. 1.
    Pont MS, Elster AD (1992) Lesions of skin and brain: modern imaging of the neurocutaneous syndromes. AJR Am J Roentgenol 158:1193–1203PubMedGoogle Scholar
  2. 2.
    Caldemeyer KS, Mirowski GW (2001) Neurofibromatosis type 1. Part I. Clinical and central nervous system manifestations. J Am Acad Dermatol 44:1025–1026CrossRefPubMedGoogle Scholar
  3. 3.
    Metheny LJ, Cappione AJ, Skuse GR (1995) Genetic and epigenetic mechanisms in the pathogenesis of neurofibromatosis type I. J Neuropathol Exp Neurol 54:753–760CrossRefPubMedGoogle Scholar
  4. 4.
    Shen MH, Harper PS, Upadhyaya M (1996) Molecular genetics of neurofibromatosis type 1. J Med Genet 33:2–17CrossRefPubMedGoogle Scholar
  5. 5.
    Norfray JF, Darling C, Byrd S, Ross BD, Schwalm C, Miller R, Tomita T (1999) Short TE proton MRS and neurofibromatosis type 1 intracranial lesions. J Comput Assist Tomogr 23:994–1003CrossRefPubMedGoogle Scholar
  6. 6.
    Menor F, Marti-Bonmati L, Arana E, Poyatos C, Cortina H (1998) Neurofibromatosis type 1 in children: MR imaging and follow-up studies of central nervous system findings. Eur J Radiol 26:121–131CrossRefPubMedGoogle Scholar
  7. 7.
    Herron J, Darrah R, Quaghebeur G (2000) Intra-cranial manifestations of the neurocutaneous syndromes. Clin Radiol 55:82–98CrossRefPubMedGoogle Scholar
  8. 8.
    Payne JM, Moharir MD, Webster R, North KN (2010) Brain structure and function in neurofibromatosis type 1: current concepts and future directions. J Neurol Neurosurg Psychiatry 81:304–309CrossRefPubMedGoogle Scholar
  9. 9.
    Bennett MR, Rizvi TA, Karyala S, McKinnon RD, Ratner N (2003) Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants. J Neurosci 23:7207–1732PubMedGoogle Scholar
  10. 10.
    DiPaolo DP, Zimmerman RA, Rorke LB, Zackai EH, Bilaniuk LT, Yachnis AT (1995) Neurofibromatosis type 1: pathologic substrate of high-signal-intensity foci in the brain. Radiology 195:721–724PubMedGoogle Scholar
  11. 11.
    Daginakatte GC, Gianino SM, Zhao NW, Parsadanian AS, Gutmann DH (2008) Increased c-Jun-NH2-kinase signaling in neurofibromatosis-1 heterozygous microglia drives microglia activation and promotes optic glioma proliferation. Cancer Res 68:10358–10366CrossRefPubMedGoogle Scholar
  12. 12.
    Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL (2009) Neurofibromatosis type 1 revisited. Pediatrics 123:124–133CrossRefPubMedGoogle Scholar
  13. 13.
    Moore BD, Slopis JM, SChomer D, Jackson EF, Levy BM (1996) Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology 46:1660–1668PubMedGoogle Scholar
  14. 14.
    North K, Joy P, Yuille D, Cocks N, Mobbs E, Hutchins P, McHugh K, de Silva M (1994) Specific learning disability in children with neurofibromatosis type 1: significance of MRI abnormalities. Neurology 44:878–883PubMedGoogle Scholar
  15. 15.
    Denckla MB, Hofman K, Mazzocco MM, Melhem E, Reiss AL, Bryan RN, Harris EL, Lee J, Cox CS, Schuerholz LJ (1996) Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1. Am J Med Genet 67:98–102CrossRefPubMedGoogle Scholar
  16. 16.
    Goh WH, Khong PL, Leung CS, Wong VC (2004) T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function. J Child Neurol 19:853–858PubMedGoogle Scholar
  17. 17.
    Castillo M, Green C, Kwock L, Smith K, Wilson D, Schiro S, Greenwood R (1995) Proton MR spectroscopy in patients with neurofibromatosis type 1: evaluation of hamartomas and clinical correlation. AJNR Am J Neuroradiol 16:141–147PubMedGoogle Scholar
  18. 18.
    Itoh T, Magnaldi S, White RM, Denckla MB, Hofman K, Naidu S, Bryan RN (1994) Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities. AJNR Am J Neuroradiol 15:1513–1519PubMedGoogle Scholar
  19. 19.
    Gonen O, Wang ZJ, Viswanathan AK, Molloy PT, Zimmerman RA (1999) Three-dimensional multivoxel proton MR spectroscopy of the brain in children with neurofibromatosis type 1. AJNR Am J Neuroradiol 20:1333–1341PubMedGoogle Scholar
  20. 20.
    Sevick RJ, Barkovich AJ, Edwards MS, Koch T, Berg B, Lempert T (1992) Evolution of white matter lesions in neurofibromatosis type 1: MR findings. AJR Am J Roentgenol 159:171–175PubMedGoogle Scholar
  21. 21.
    Kim G, Mehta M, Kucharczyk W, Blaser S (1998) Spontaneous regression of a tectal mass in neurofibromatosis 1. AJNR Am J Neuroradiol 19:1137–1139PubMedGoogle Scholar
  22. 22.
    Wilkinson ID, Griffiths PD, Wales JK (2001) Proton magnetic resonance spectroscopy of brain lesions in children with neurofibromatosis type 1. Mag Reson Imaging 19:1081–1089CrossRefGoogle Scholar
  23. 23.
    Hyman SL, Gill DS, Shores EA, Steinberg A, North KN (2007) T2 hyperintensities in children with neurofibromatosis type 1 and their relationship to cognitive functioning. J Neurol Neurosurg Psychiatry 78:1088–1091CrossRefPubMedGoogle Scholar
  24. 24.
    Wang PY, Kaufmann WE, Koth CW, Denckla MB, Barker PB (2000) Thalamic involvement in neurofibromatosis type 1: evaluation with proton magnetic resonance spectroscopic imaging. Ann Neurol 47:477–484CrossRefPubMedGoogle Scholar
  25. 25.
    Jones AP, Gunawardena WJ, Coutinho CM (2001) 1H MR spectroscopy evidence for the varied nature of asymptomatic focal brain lesions in neurofibromatosis type 1. Neuroradiology 43:62–67CrossRefPubMedGoogle Scholar
  26. 26.
    National Institutes of Health Consensus Development Conference (1988) Neurofibromatosis: conference statement. Arch Neurol 45:575–578Google Scholar
  27. 27.
    Schrimsher GW, Billingsley RL, Slopis JM, Moore BD (2003) Visual-spatial performance deficits in children with neurofibromatosis type-1. Am J Med Genet 120A:326–330CrossRefPubMedGoogle Scholar
  28. 28.
    Sastre-Garriga J, Ingle GT, Chard DT, Ramió-Torrentà L, McLean MA, Miller DH, Thompson AJ (2005) Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 62:569–573CrossRefPubMedGoogle Scholar
  29. 29.
    Alkan A, Sarac K, Kutlu R, Yakinci C, Sigirci A, Aslan M, Ozcan H, Yologlu S (2003) Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1. Mag Reson Imaging 21:1049–1053CrossRefGoogle Scholar
  30. 30.
    Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ (2008) Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 135:549–560CrossRefPubMedGoogle Scholar
  31. 31.
    Chatham JC, Blackband SJ (2001) Nuclear magnetic resonance spectroscopy and imaging in animal research. ILAR J 42:189–208PubMedGoogle Scholar
  32. 32.
    Zhu Y, Harada T, Liu L, Lush ME, Guignard F, Harada C, Burns DK, Bajenaru ML, Gutmann DH, Parada LF (2005) Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation. Development 132:5577–5588CrossRefPubMedGoogle Scholar
  33. 33.
    Brown JA, Emnett RJ, White CR, Yuede C, Conyers S, O'Malley KL, Wozniak DF, Gutmann DH (2010) Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Hum Mol Genet 7. doi: 10.1093/hmg/ddq382
  34. 34.
    Gill DS, Hyman SL, Steinberg A, North KN (2006) Age-related findings on MRI in neurofibromatosis type 1. Pediatr Radiol 36:1048–1056CrossRefPubMedGoogle Scholar
  35. 35.
    Van der Werf YD, Witter MP, Uylings HB, Jolles J (2000) Neuropsychology of infarctions in the thalamus: a review. Neuropsychologia 38:613–627CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Charlotte Barbier
    • 1
  • Camille Chabernaud
    • 2
  • Laurent Barantin
    • 1
  • Philippe Bertrand
    • 3
  • Catherine Sembely
    • 4
  • Dominique Sirinelli
    • 4
  • Pierre Castelnau
    • 2
    • 5
    • 6
    Email author
  • Jean-Philippe Cottier
    • 1
    • 5
  1. 1.Department of NeuroradiologyCHRU & Tours UniversityToursFrance
  2. 2.Department of Pediatric NeurologyCHRU & Tours University and INSERM U930ToursFrance
  3. 3.Department of RadiologyCHRU & Tours UniversityToursFrance
  4. 4.Department of Pediatric RadiologyCHRU & Tours UniversityToursFrance
  5. 5.CHRU & Tours University and INSERM U930ToursFrance
  6. 6.Neurologie Pediatrique & INSERM U930, Hopital d’Enfants Gatien de ClochevilleTours cedex 09France

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