Diffusion tensor imaging–based analysis of baseline neurocognitive function and post-treatment white matter changes in pediatric patients with craniopharyngioma treated with surgery and proton therapy

Abstract Purpose To determine the pre-irradiation baseline association of white matter integrity with neurocognitive function and to assess post-treatment changes in pediatric patients with craniopharyngioma treated with proton therapy. Methods and Materials Ninety children and adolescents (aged 2-20 years) with craniopharyngioma were treated with proton therapy [54 Gy(RBE)] in a prospective therapeutic trial. Neurocognitive performance at the postoperative baseline before proton therapy and diffusion tensor imaging (DTI) data acquired at baseline and at annual follow-up were analyzed. Tract-based spatial statistics (TBSS) and structural connectomics were employed to derive global and local white matter features from DTI. Baseline DTI features were compared for patients with average and below-average neurocognitive performance. Longitudinal DTI data were analyzed to determine the proton dose effect on white matter structures in relation to the irradiated brain volume and baseline age. Results Before proton therapy, patients with below-average working memory, processing speed, verbal fluency, verbal learning, and/or fine motor dexterity exhibited more globally degraded white matter structures when compared to their counterparts with average performance, as indicated by lower mean fractional anisotropy, decreased global efficiency, or higher modularity. Surgery, obstructive hydrocephalus, and preoperative hypothalamic involvement appeared to be related to this degradation. In local analyses, TBSS revealed left-lateralized associations with verbal and motor functions, which supported surgical approaches to midline tumors via the right hemisphere. The mean fractional anisotropy of the brain and the global efficiency derived from DTI increased over the 5 years after proton therapy. The rate of increase was lower with larger irradiated brain volumes and in older children. Conclusions Below-average baseline neurocognitive performance in patients with craniopharyngioma before proton therapy appeared to be related to structural degradation of white matter tracts. Post-therapy longitudinal DTI showed improving trends in global integrity and efficiency measures, particularly in children in whom a smaller brain volume was irradiated.