Diffusion tensor MR imaging of treatment-induced white matter injury in childhood cancer survivors: clinical and translational studies.

Abstract

Diffusion tensor MR imaging (DTI) is based on the diffusion of water molecules in the brain, and advantageous for evaluating white matter pathology as the diffusion process in white matter is highly directional (anisotropic) due to axonal fibers running in parallel. We evaluated its novel role as a marker for treatment-induced neurotoxicity in childhood cancer (medulloblastoma and acute lymphoblastic leukemia) survivors, and then performed translational studies using an animal model of radiation-induced white matter injury to elucidate the histological correlates of the diffusion tensor indices. We found DTI indices to be associated with known neurotoxicity risk factors, and neurocognitive scores in children. In translational studies, the longitudinal changes of DTI indices reflected the histopathological changes of myelination, axonal damage, astrogliosis and necrosis. Hence, our results support the use of DTI to probe white matter microstructure, and as a biomarker to monitor radiation-induced white matter damage.