Quantitative MRI assessments of white matter in children treated for acute lymphoblastic leukemia

摘要

The purpose of this study was to use objective quantitative MR imaging methods to prospectively assess changes in thernphysiological structure of white matter during the temporal evolution of leukoencephalopathy (LE) in children treated forrnacute lymphoblastic leukemia. The longitudinal incidence, extent (proportion of white matter affect), and intensityrn(elevation of T1 and T2 relaxation rates) of LE was evaluated for 44 children. A combined imaging set consisting of T1,rnT2, PD, and FLAIR MR images and white matter, gray matter and CSF a priori maps from a spatially normalized atlasrnwere analyzed with a neural network segmentation based on a Kohonen Self-Organizing Map (SOM). Quantitative T1rnand T2 relaxation maps were generated using a nonlinear parametric optimization procedure to fit the correspondingrnmulti-exponential models. A Cox proportional regression was performed to estimate the effect of intravenousrnmethotrexate (IV-MTX) exposure on the development of LE followed by a generalized linear model to predict thernprobability of LE in new patients. Additional T-tests of independent samples were performed to assess differences inrnquantitative measures of extent and intensity at four different points in therapy. Higher doses and more courses of IVMTXrnplaced patients at a higher risk of developing LE and were associated with more intense changes affecting more ofrnthe white matter volume; many of the changes resolved after completion of therapy. The impact of these changes onrnneurocognitive functioning and quality of life in survivors remains to be determined.