Multimodal imaging with magnetization transfer and diffusion tensor imaging reveals evidence of myelin damage in children and youth treated for a brain tumor

Abstract

Abstract Background The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI. Methods Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial–spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI— fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls. Results MTR was decreased across multiple white matter tracts in patients when compared to healthy children, P < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, P < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, Ps < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, Ps < .01, but not healthy control children. Conclusions Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.