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White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia:
Winnie C W Chu1, Ki-Wai Chik, Yu-Leung Chan
1Department of Diagnostic Radiology and Organ Imaging, Medical Physics Div, Chinese Univ of Hong Kong, Prince of Wales Hosp, 30-32 Ngan Shing St, Shatin, Hong Kong SAR, China. winnie@med.cuhk.edu.hk
Insights
Magnetic resonance spectroscopy detects early brain metabolite changes in children with acute lymphoblastic leukemia treated with high-dose methotrexate, even before white matter abnormalities appear on MRI.
Area of Science:
- Pediatric Oncology
- Neuroimaging
- Biochemistry
Background:
- Acute lymphoblastic leukemia (ALL) treatment in children often involves high-dose methotrexate.
- Potential neurotoxicity of chemotherapy necessitates monitoring brain changes.
- Understanding long-term effects on developing brains is crucial.
Purpose of the Study:
- To evaluate white matter and cerebral metabolite alterations during and after chemotherapy in pediatric ALL patients.
- To compare the sensitivity of MR imaging and MR spectroscopy in detecting treatment-related brain changes.
Main Methods:
- Prospective study of 23 children with ALL undergoing MR imaging and MR spectroscopy.
- Assessments conducted at multiple time points from diagnosis up to 3 years post-treatment.
- Analysis of white matter hyperintensities and specific cerebral metabolites (NAA, choline, creatine) in the frontoparietal region.
Main Results:
- High-dose methotrexate led to significant changes in N-acetylaspartate to choline and choline to creatine ratios at 20 weeks.
- MR spectroscopy detected metabolite alterations in 81% of children, while MR imaging showed white matter changes in only 23% at 20 weeks.
- These metabolite changes showed a trend towards reversal over time, potentially influenced by age-related brain maturation.
Conclusions:
- MR spectroscopy is a more sensitive tool than MR imaging for detecting early brain effects of high-dose methotrexate in children with ALL.
- Metabolite changes observed via MR spectroscopy may precede visible structural white matter abnormalities.
- This suggests MR spectroscopy can aid in monitoring neurotoxicity during ALL treatment.
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.