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Detection and characterization of neurotoxicity in cancer patients using proton MR spectroscopy

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Abstract

Objective

The study objective was to detect abnormalities and identify relationships between brain metabolic ratios determined by proton magnetic resonance spectroscopic imaging (1H-MRSI) and neuropsychological (NP) function in cancer patients at risk for neurotoxicity.

Methods

Thirty-two patients received 1H-MRSI using a multi-slice, multi-voxel technique on a 1.5T magnet. Cho/NAA, NAA/Cr, and Cho/Cr ratios were identified in seven pre-determined sites without tumor involvement. A battery of age-appropriate NP tests was administered within 7 days of imaging. Relationships were examined between test scores and metabolite ratios.

Conclusions

This study identifies relationships between brain metabolite ratios and cognitive functioning in cancer patients. 1H-MRSI may be useful in early detection of neurotoxic effects, but prospective longitudinal studies in a homogeneous population are recommended to determine the prognostic value.

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References

  1. Anderson NE (2003) Late complications in childhood central nervous system tumour survivors. Curr Opin Neurol 16(6):677–683, DOI 10.1097/00019052-200312000-00006

    Article  PubMed  Google Scholar 

  2. Aydin K, Bakir B, Tatli B, Terzibasioglu E, Ozmen M (2005) Proton MR spectroscopy in three children with Tay-Sachs disease. Pediatr Radiol 35(11):1081–1085, DOI 10.1007/s00247-005-1542-3

    Article  PubMed  Google Scholar 

  3. Bleyer WA, Fallavollita J, Robison L, Balsom W, Meadows A, Heyn R, Sitars A, Ortega J, Miller D, Constine L et al (1990) Influence of age, sex, and concurrent intrathecal methotrexate therapy on intellectual function after cranial irradiation during childhood: a report from the Children’s Cancer Study Group. Pediatr Hematol Oncol 7(4):329–338

    Article  PubMed  CAS  Google Scholar 

  4. Brown MS, Stemmer SM, Simon JH, Stears JC, Jones RB, Cagnoni PJ, Sheeder JL (1998) White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy. AJNR American J Neuroadiol 19(2):217–221

    CAS  Google Scholar 

  5. Chen CY, Zimmerman RA, Faro S, Bilaniuk LT, Chou TY, Molloy PT (1996) Childhood leukemia: central nervous system abnormalities during and after treatment. AJNR Am J Neuroradiol 17(2):295–310

    PubMed  CAS  Google Scholar 

  6. Chu W, Chick K, Chan Y, Yeung D, Roebuck D, Howard R, Li C, Metreweli C (2003) White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR Imaging and 1H-MR Spectroscopy. Radiology 229:659–669, DOI 10.1148/radiol.2293021550

    Article  PubMed  Google Scholar 

  7. Cecil KM, Lenkinski RE (1998) Proton MR spectroscopy in inflammatory and infectious brain disorders. Neuroimaging Clin N Am 8(4):863–880

    PubMed  CAS  Google Scholar 

  8. Davidson A, Payne G, Leach MO, McVicar D, Britton JM, Watson M, Tait DM (2000) Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer. Med Pediatr Oncol 35(1):28–34

    Article  PubMed  CAS  Google Scholar 

  9. Davidson A, Tait DM, Payne GS, Hopewell JW, Leach MO, Watson M, MacVicar AD, Britoon JA, Ashley S (2000) Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer. Br J Radiol 73(868):421–424

    PubMed  CAS  Google Scholar 

  10. Delis DC, Kramer J, Kaplan E, Ober BA (1994) California Verbal Learning Test, Children’s Version. Psychological Corporation, San Antonio, TX

    Google Scholar 

  11. Delis D, Kramer J, Kaplan E, Ober BA (2000) California Verbal Learning Test, 2nd edn. Psychological Corporation, San Antonio, TX

    Google Scholar 

  12. Duyn JH, Gillen J, Sobering G, van Zijl PC, Moonen CT (1993) Multisection proton MR spectroscopic imaging of the brain. Radiology 188(1):277–282

    PubMed  CAS  Google Scholar 

  13. Eiser C, Tillmann V (2001) Learning difficulties in children treated for acute lymphoblastic leukaemia (ALL). Pediatr Rehabil 4(3):105–118, DOI 10.1080/13638490110064806

    Article  PubMed  CAS  Google Scholar 

  14. Fayed N, Modrego PJ, Castillo J, Davilla J (2007) Evidence of brain dysfunction in attention deficit-hyperactivity disorder: A controlled study with proton magnetic resonance spectroscopy. Acad Radiol 14(9):1029–1035, DOI 10.1016/j.acra.2007.05.017

    Article  PubMed  Google Scholar 

  15. Garcia-Perez A, Sierrasesumaga L, Narbona-Garcia J, Calvo-Manuel F, Aguirre-Ventallo M (1994) Neuropsychological evaluation of children with intracranial tumors: impact of treatment modalities. Med Pediatr Oncol 23(2):116–123

    Article  PubMed  CAS  Google Scholar 

  16. Hanefeld F, Brockmann K, Dechent P (2005) MR spectroscopy in pediatric white matter disease. In: Gillard J, Waldman A, Barker P (eds) Clinical MR neuroimaging: Diffusion, perfusion, and spectroscopy. Cambridge University Press, Cambridge, U.K., pp 755–778

    Google Scholar 

  17. Hunter JV, Thornton RJ, Wang ZJ, Levin HS, Roberson G, Brooks WM, Swank PR (2005) Late proton MR spectroscopy in children after traumatic brain injury: correlation with cognitive outcomes. AJNR Am J Neuroradiol 26(3):482–488

    PubMed  Google Scholar 

  18. Iuvone L, Mariotti P, Colosimo C, Guzzetta F, Ruggiero A, Riccardi R (2002) Long-term cognitive outcome, brain computed tomography scan, and magnetic resonance imaging in children cured for acute lymphoblastic leukemia. American Cancer Society 95(12):2562–2570

    Google Scholar 

  19. Lu D, Pavlakis SG, Frank Y, Bakshi S, Pahwa S, Gould RJ, Sison C, Hsu C, Lesser M, Hoberman M, Barnett T, Hyman RA (1996) Proton MR spectroscopy of the basal ganglia in healthy children and children with AIDS. Radiology 199:423–428

    PubMed  CAS  Google Scholar 

  20. McCarthy D (1972) McCarthy Scales of Children’s Abilities. Psychological Corporation, San Antonio, TX

    Google Scholar 

  21. Magalhaes A, Godfrey W, Shen Y, Hu J, Smith W (2005) Proton magnetic resonance spectroscopy of brain tumors correlated with pathology. Acad Radiol 12(1):51–57

    Article  PubMed  Google Scholar 

  22. Miller BL (1991) A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 4(2):47–52, DOI 10.1016/j.acra.2004.10.057

    Article  PubMed  CAS  Google Scholar 

  23. Mulhern RK, Palmer SL, Reddick WE, Glass JO, Kun LE, Taylor J, Langson J, Gajjar A (2001) Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. J Clin Oncol 19(2):472–429

    PubMed  CAS  Google Scholar 

  24. Nakayama M, Tavora DG, Alvim TC, Araujo AC, Gama RL (2006) MRI and 1H-MRS findings of three patients with Sjogren-Larsson syndrome. Arq Neuropsiquiatr 64(2B):398–401, DOI 10.1590/S0004-282X2006000300009

    PubMed  Google Scholar 

  25. Nathan PC, Whitcomb T, Wolters PL, Steinberg SM, Balis FM, Brouwers P, Hunsberger S, Feusner J, Sather H, Miser J, Odom LF, Poplack D, Reaman G, Bleyer WA (2006) Very high-dose methotrexate (33.6 g/m2) as CNS preventive therapy for childhood acute lymphoblastic leukemia: results of National Cancer Institute/Children’s Cancer Group trials CCG-191P, CCG-134P, and CCG-144P. Leuk Lymphoma 47(12):2488–2504

    Article  PubMed  CAS  Google Scholar 

  26. Packer RJ, Sutton LN, Atkins TE, Radcliffe J, Bunin GR, D’Angio G, Siegel KR, Schut L (1989) A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70(5):707–713

    PubMed  CAS  Google Scholar 

  27. Psychological Corporation (1999) Wechsler Abbreviated Scale of Intelligence. Harcourt Brace, San Antonio, TX

    Google Scholar 

  28. Reddick W, Shan Z, Glass J, 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. Am Cancer Soc 106(4):941–949

    Google Scholar 

  29. Reimers TS, Ehrenfels S, Mortensen EL, Schmiegelow M, Sonderkaer S, Cartensen H, Schmiegelow K, Muller J (2003) Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors. Med Pediatr Oncol 40(1):26–34

    Article  PubMed  Google Scholar 

  30. Reitan R, Davidson L (1974) Clinical Neuropsychology: Current Status and Applications. Wiley, New York

    Google Scholar 

  31. Shih MT, Singh AK, Wang AM, Patel S (2004) Brain lesions with elevated lactic acid peaks on magnetic resonance spectroscopy. Curr Probl Diagn Radiol 33(2):85–95, DOI 10.1016/j.cpradiol.2003.11.002

    Article  PubMed  Google Scholar 

  32. Smith JK, Castillo M, Kwock L (2003) MR spectroscopy of brain tumors. Magn Reson Imaging Clin N Am 11(3):415–429, v–vi DOI 10.1016/S1064-9689(03)00061-8

    Article  PubMed  Google Scholar 

  33. Tedeschi G, Bonavita S (2005) MR spectroscopy in demyelination and inflammation. In: Gillard J, Waldman A, Barker P (eds) Clinical MR Neuroimaging: Diffusion, Perfusion, and Spectroscopy. Cambridge University Press, Cambridge, U.K., pp 429–443

    Google Scholar 

  34. Tzika AA, Ball WS Jr., Vigneron DB, Dunn RS, Nelson SJ, Kirks DR (1993) Childhood adrenoleukodystrophy: assessment with proton MR spectroscopy. Radiology 189(2):467–480

    PubMed  CAS  Google Scholar 

  35. Urenjak J, Williams SR, Gadian DG, Noble M (1992) Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. J Neurochem 59(1):55–61

    Article  PubMed  CAS  Google Scholar 

  36. Waldman AD, Rai GS (2003) The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer’s disease and vascular dementia: a proton magnetic resonance spectroscopy study. Neuroradiology 45(8):507–512, DOI 10.1007/s00234-003-1040-y

    Article  PubMed  CAS  Google Scholar 

  37. Warren K, Hill R, Black J, Aikin A, Wolters P, Shimoda K, Balis F (2004) Evaluating Neurotoxicity in Cancer Patients. Neuro-Oncology 6(4):435, (abstract)

    Google Scholar 

  38. Wilkinson GS (1993) Wide Range Achievement Test Administration Manual, 3rd edn. Wide Range, Wilmington

    Google Scholar 

  39. Wechsler D (1997) Wechsler Adult Intelligence Scale, 3rd edn. Psychological Corporation, San Antonio, TX

    Google Scholar 

  40. Wechsler D (1991) Wechsler Intelligence Scale for Children, 3rd edn. Psychological Corporation, San Antonio, TX

    Google Scholar 

  41. Wechsler D (1989) Wechsler Preschool and Primary Scale of Intelligence—Revised. Psychological Corporation, San Antonio, TX

    Google Scholar 

  42. Willemsen MA, Van Der Graaf M, Van Der Knaap MS, Heerschap A, Van Domburg PH, Gabreels FJ, Rotteveel JJ (2004) MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol 25(4):649–657

    PubMed  Google Scholar 

  43. Yeo RA, Brooks WM, Jung RE (2006) NAA and higher cognitive function in humans. Adv Exp Med Biol 576:215–226

    Article  PubMed  CAS  Google Scholar 

  44. Zaroff CM, Neudorfer O, Morrison C, Pastores GM, Rubin H, Kolodny EH (2004) Neuropsychological assessment of patients with late onset GM2 gangliosidosis. Neurology 62(12):2283–2286

    PubMed  CAS  Google Scholar 

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Acknowledgments

Statistical analysis performed by Dr. Paul Albert, Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD. This research was supported in part by the National Cancer Institute contracts #N01-SC-71102, #N01-SC-07006, and #HHSN261200477004C with the Medical Illness Counseling Center and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The views expressed do not necessarily represent the views of the National Institutes of Health or the United States Government.

Disclosure

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD, USA

    Emilie A. Steffen-Smith, Pamela L. Wolters & Katherine E. Warren

  2. Medical Illness Counseling Center, Chevy Chase, MD, USA

    Pamela L. Wolters

  3. Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Paul S. Albert

  4. Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Eva H. Baker

  5. Children’s National Medical Center, Washington, DC, USA

    Kim C. Shimoda

  6. National Institute of Mental Health, CBDB, National Institutes of Health, Bethesda, MD, USA

    Alan S. Barnett

  7. Pediatric Oncology Branch, National Cancer Institute, Building 10/Room 1-3940, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Katherine E. Warren

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  1. Emilie A. Steffen-Smith
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Correspondence to Katherine E. Warren.

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Steffen-Smith, E.A., Wolters, P.L., Albert, P.S. et al. Detection and characterization of neurotoxicity in cancer patients using proton MR spectroscopy. Childs Nerv Syst 24, 807–813 (2008). https://doi.org/10.1007/s00381-007-0576-2

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  • DOI: https://doi.org/10.1007/s00381-007-0576-2

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