Reduced brain microstructural asymmetry in patients with childhood leukemia treated with chemotherapy compared with healthy controls

Microstructural asymmetry of the brain can provide more direct causal explanations of functional lateralization than can macrostructural asymmetry. We performed a cross-sectional diffusion imaging study of 314 patients treated for childhood acute lymphoblastic leukemia (ALL) at a single institution and 92 healthy controls. An asymmetry index based on diffusion metrics was computed to quantify brain microstructural asymmetry. The effects of age and the asymmetry metrics of the two cohorts were examined with t-tests and linear models. We discovered two new types of microstructural asymmetry. Myelin-related asymmetry in controls was prominent in the back brain (89% right), whereas axon-related asymmetry occurred in the front brain (67% left) and back brain (88% right). These asymmetries indicate that white matter is more mature and more myelinated in the left back brain, potentially explaining the leftward lateralization of language and visual functions. The asymmetries increase throughout childhood and adolescence (P = 0.04) but were significantly less in patients treated for ALL (P<0.01), especially in younger patients. Our results indicate that atypical brain development may appear long before patients treated with chemotherapy become symptomatic.