White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy.

Abstract

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