Reliably detecting subtle therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its nearly identical MR properties and location with unmyelinated white matter. T1, T2, PD, and FLAIR images were collected for 44 children aged 1.7-18.7 (median 5.9) years near the start of therapy for ALL. The ICBM atlas and corresponding apriori maps were spatially normalized to each patient and resliced using SPM99 software. A combined imaging set consisting of MR images and WM, GM and CSF apriori maps were then analyzed with a Kohonen Self-Organizing Map. Vectors from hyperintense regions were compared to normal appearing genu vectors from the same patient. Analysis of the distributions of the differences, calculated on T2 and FLAIR images, revealed two distinct groups. The first large group, assumed normal unmyelinated white matter, consisted of 37 patients with changes in FLAIR ranging from 80 to 147 (mean 117∓17) and T2 ranging from 92 to 217 (mean 144∓28). The second group, assumed leukoencephalopathy, consisted of seven patients with changes in FLAIR ranging from 154 to 196 (mean 171∓19) and T2 ranging from 190 to 287 (mean 216∓33). A threshold was established for both FLAIR (change > 150) and T2 (change > 180).