Skip main navigation
Close Drawer MenuOpen Drawer Menu
Search
Quick Search in Journals
Quick Search anywhere
Advanced Search
Menu
  • Information
    • Previous
    Next
    Pediatric Imaging

    White Matter and Cerebral Metabolite Changes in Children Undergoing Treatment for Acute Lymphoblastic Leukemia: Longitudinal Study with MR Imaging and 1H MR Spectroscopy

    Published Online:Dec 1 2003https://doi.org/10.1148/radiol.2293021550

    Abstract

    PURPOSE: To assess the development of white matter and cerebral metabolite changes during and after treatment in children with acute lymphoblastic leukemia.

    MATERIALS AND METHODS: Twenty-three children (10 boys, mean age of 6.3 years; 13 girls, mean age of 6.6 years) with acute lymphoblastic leukemia were examined prospectively with magnetic resonance (MR) imaging and MR spectroscopy at 0, 8, and 20 weeks and 1, 2, and 3 years after diagnosis. White matter changes were diagnosed on the basis of hyperintense abnormalities on T2-weighted MR images. Single-voxel hydrogen 1 MR spectroscopy results from the right frontoparietal region of 21 children who received intravenous high-dose methotrexate were analyzed for cerebral metabolite changes. Multilevel models were used to assess the change in metabolites from baseline levels at subsequent follow-up.

    RESULTS: At 20 weeks, MR spectroscopy showed a significant reduction (P < .05) of mean N-acetylaspartate to choline ratio and increase in mean choline to creatine ratio (P < .05) in the children given high-dose methotrexate. This decline in N-acetylaspartate to choline ratio subsequently reversed and increased, possibly because of normal age-related brain maturation. Seventeen of 21 (81%) children showed metabolite changes at MR spectroscopy, while five of 22 (23%) showed white matter changes at MR imaging at 20 weeks. One more child developed white matter changes at 32 weeks. The associated changes resolved or reduced with time.

    CONCLUSION: MR spectroscopy demonstrated metabolite changes in the brain after high-dose methotrexate treatment in the absence of structural white matter abnormalities at MR imaging. MR spectroscopy might thus be a more sensitive method of monitoring the effects of high-dose methotrexate in the brain.

    © RSNA, 2003

    References

    • 1 Schroeder H, Garwicz S, Kristinsson J, Siimes MA, Wesenberg F, Gustafsson G. Outcome after first relapse in children with acute lymphoblastic leukemia: a population-based study of 315 patients from the Nordic Society of Pediatric Hematology and Oncology. Med Pediatr Oncol 1995; 25:372-378. Crossref, Medline, Google Scholar
    • 2 Evans AE, Gilbert ES, Zandstra R. The increasing incidence of central nervous system leukemia in children: Children’s Cancer Study Group A. Cancer 1970; 26:404-409. Crossref, Medline, Google Scholar
    • 3 West RJ, Graham-Pole J, Hardisty RM, Pike MC. Factors in pathogenesis of central-nervous-system leukaemia. BMJ 1972; 3:311-314. Crossref, Medline, Google Scholar
    • 4 Nesbit ME, Jr, Sather HN, Robison LL, et al. Presymptomatic central nervous system therapy in previously untreated childhood acute lymphoblastic leukemia: comparison of 1800 rad and 2400 rad: a report for Children’s Cancer Study Group. Lancet 1981; 1:461-466. Medline, Google Scholar
    • 5 Eden OB, Lilleyman JS, Richards S, Shaw MP, Peto J. Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood). Br J Haematol 1991; 78:187-196. Crossref, Medline, Google Scholar
    • 6 Paakko E, Talvensaari K, Pyhtinen J, Lanning M. Late cranial MRI after cranial irradiation in survivors of childhood cancer. Neuroradiology 1994; 36:652-655. Crossref, Medline, Google Scholar
    • 7 Laitt RD, Chambers EJ, Goddard PR, Wakeley CJ, Duncan AW, Foreman NK. Magnetic resonance imaging and magnetic resonance angiography in long term survivors of acute lymphoblastic leukemia treated with cranial irradiation. Cancer 1995; 76:1846-1852. Crossref, Medline, Google Scholar
    • 8 Hill JM, Kornblith AB, Jones D, et al. A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation. Cancer 1998; 82:208-218. Crossref, Medline, Google Scholar
    • 9 Lien HH, Blomlie V, Saeter G, Solheim O, Fossa SD. Osteogenic sarcoma: MR signal abnormalities of the brain in asymptomatic patients treated with high-dose methotrexate. Radiology 1991; 179:547-550. Link, Google Scholar
    • 10 Allen JC, Rosen G, Mehta BM, Horten B. Leukoencephalopathy following high-dose iv methotrexate chemotherapy with leucovorin rescue. Cancer Treat Rep 1980; 64:1261-1273. Medline, Google Scholar
    • 11 Wilson DA, Nitschke R, Bowman ME, Chaffin MJ, Sexauer CL, Prince JR. Transient white matter changes on MR images in children undergoing chemotherapy for acute lymphocytic leukemia: correlation with neuropsychologic deficiencies. Radiology 1991; 180:205-209. Link, Google Scholar
    • 12 Paakko E, Vainionpaa L, Lanning M, Laitinen J, Pyhtinen J. White matter changes in children treated for acute lymphoblastic leukemia. Cancer 1992; 70:2728-2733. Crossref, Medline, Google Scholar
    • 13 Matsumoto K, Takahashi S, Sato A, et al. Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy: an MR analysis. Int J Radiat Oncol Biol Phys 1995; 32:913-918. Crossref, Medline, Google Scholar
    • 14 Chan YL, Roebuck DJ, Yuen MP, et al. Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis. Int J Radiat Oncol Biol Phys 2001; 50:759-763. Crossref, Medline, Google Scholar
    • 15 Bleyer WA. Leukoencepalopathy detectable by magnetic resonance imaging: much ado about nothing? Regarding Matsumoto et al, IJROBP 32:913–918;1995. Int J Radiat Oncol Biol Phys 1995; 32:1251-1252. Crossref, Medline, Google Scholar
    • 16 Kingma A, Mooyaart EL, Kamps WA, Nieuwenhuizen P, Wilmink JT. Magnetic resonance imaging of the brain and neuropsychological evaluation in children treated for acute lymphoblastic leukemia at a young age. Am J Pediatr Hematol Oncol 1993; 15:231-238. Crossref, Medline, Google Scholar
    • 17 Harila-Saari AH, Paakko EL, Vainionpaa LK, Pyhtinen J, Lanning BM. A longitudinal magnetic resonance imaging study of the brain in survivors of childhood acute lymphoblastic leukemia. Cancer 1998; 83:2608-2617. Crossref, Medline, Google Scholar
    • 18 Eden OB, Harrison G, Richards S, et al. Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980–1997: Medical Research Council Childhood Leukaemia Working Party. Leukemia 2000; 14:2307-2320. Crossref, Medline, Google Scholar
    • 19 Hann I, Vora A, Harrison G, et al. Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol. Br J Haematol 2001; 113:103-114. Crossref, Medline, Google Scholar
    • 20 Schrappe M, Reiter A, Zimmermann M, et al. Long-term results of four consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 1995: Berlin-Frankfurt-Munster. Leukemia 2000; 14:2205-2222. Crossref, Medline, Google Scholar
    • 21 Vanhamme L, van den Boogaart A, Van Huffel S. Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 1997; 129:35-43. Crossref, Medline, Google Scholar
    • 22 van den Boogaart A, Howe FA, Rodrigues LM, Stubbs M, Griffiths JR. In vivo 31P MRS: absolute concentrations, signal-to-noise and prior knowledge. NMR Biomed 1995; 8:87-93. Crossref, Medline, Google Scholar
    • 23 Goldstein H. Multilevel statistical models London, England: Edward Arnold, 1995. Google Scholar
    • 24 Ochs JJ, Parvey LS, Whitaker JN, et al. Serial cranial computed-tomography scans in children with leukemia given two different forms of central nervous system therapy. J Clin Oncol 1983; 1:793-798. Crossref, Medline, Google Scholar
    • 25 Paakko E, Harila-Saari A, Vanionpaa L, Himanen S, Pyhtinen J, Lanning M. White matter changes on MRI during treatment in children with acute lymphoblastoic leumemia: correlation with neuropsychological findings. Med Pediatr Oncol 2000; 35:456-461. Crossref, Medline, Google Scholar
    • 26 Jaffe N, Takaue Y, Anzai T, Robertson R. Transient neurologic disturbances induced by high-dose methotrexate treatment. Cancer 1985; 56:1356-1360. Crossref, Medline, Google Scholar
    • 27 Yim YS, Maboney DH, Jr, Oshman DG. Hemiparesis and ischemic changes of the white matter after intrathecal therapy for children with acute lymphocytic leukemia. Cancer 1991; 67:2058-2061. Crossref, Medline, Google Scholar
    • 28 Ebner F, Ranner G, Slavc I, et al. MR findings in methotrexate-induced CNS abnormalities. AJNR Am J Neuroradiol 1989; 10:959-964. Medline, Google Scholar
    • 29 Van der Knaap MS, va der Grond J, van Rijen PC, Faber JA, Valk J, Willemse K. Age-dependent changes in localized proton and phosphorus MR spectroscopy of the brain. Radiology 1990; 176:509-515. Link, Google Scholar
    • 30 Roser W, Hagberg G, Mader I, et al. Proton MRS of gadolinium-enhancing MS plaques and metabolic changes in normal-appearing white matter. Magn Reson Med 1995; 33:811-817. Crossref, Medline, Google Scholar
    • 31 Davies SE, Newcombe J, Williams SR, MacDonald WI, Clark JB. High resolution proton NMR spectroscopy of multiple sclerosis lesions. J Neurochem 1995; 64:742-748. Medline, Google Scholar
    • 32 Davie CA, Hawkins CP, Barker GJ, et al. Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 1994; 117:49-58. Crossref, Medline, Google Scholar
    • 33 Esteve F, Rubin C, Grand S, Kolodie H, Le Bas JF. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy. Int J Radiat Oncol Biol Phys 1998; 40:279-286. Crossref, Medline, Google Scholar
    • 34 Grossman RI, Lenkinski RE, Ramer KN, Gonzalez-Scarano F, Cohen JA. MR proton spectroscopy in multiple sclerosis. AJNR Am J Neuroradiol 1992; 13:1535-1543. Medline, Google Scholar
    • 35 Waldrop SM, Davis PC, Padgett CA, Shapiro MB, Morris R. Treatment of brain tumours in children is associated with abnormal MR spectroscopic ratios in brain tissue remote from the tumour site. AJNR Am J Neuroradiol 1998; 19:963-970. Medline, Google Scholar
    • 36 Kramer JH, Norman D, Brant-Zawadzki M, Ablin A, Moore IM. Absence of white matter changes on magnetic resonance imaging in children treated with CNS prophylaxis therapy for leukemia. Cancer 1988; 61:928-930. Crossref, Medline, Google Scholar
    • 37 Rajanayagam V, Grad J, Krivit W, et al. Proton MR spectroscopy of childhood adrenoleukodystrophy. AJNR Am J Neuroradiol 1996; 17:1013-1024. Medline, Google Scholar
    • 38 Hitosugi M, Ichijo M, Matsuoka Y, Takenaka N, Fujii H. Proton MR spectroscopy findings in herpes simplex encephalitis. Rinsho Shinkeigaku 1996; 36:839-843. Medline, Google Scholar
    • 39 Chan YL, Yeung DK, Leung SF, Cao G. Proton magnetic resonance spectroscopy of late delayed radiation-induced injury of the brain. J Magn Reson Imaging 1999; 10:130-137. Crossref, Medline, Google Scholar
    • 40 Gonen O, Murdoch JB, Stoyanova R, Goelman G. 3D multivoxel proton spectroscopy of human brain using a hybrid of 8th-order Hadamard encoding with 2D chemical shift imaging. Magn Reson Med 1998; 39:34-40. Crossref, Medline, Google Scholar

    Article History

    Published in print: Dec 2003