The Association of Radiation Dose with Hippocampal Volume Changes in Pediatric Patients as Quantified by Automated Software

Although hippocampal (HC) dose is associated with volume loss and cognitive function in adults, evaluation of radiation-induced changes to the HC in children is complicated by continued growth of the pediatric brain. In addition, labor intensive manual quantification of HC volumes has limited ability to follow changes over time. NeuroQuant (NQ), an FDA-approved software used for the quantification of HC volumes in adult dementia, provides an automated volumetric analysis based on MRI of brain sub-structures as well as comparison to normative data. Here we report novel use of this software for rapid automated measurement of HC volume changes in pediatric patients undergoing cranial radiation. Specifically, this study aimed to assess changes in HC volumes after cranial radiation and correlation of these changes with radiation dosimetry. Pediatric patients treated with proton beam radiotherapy in 2015 and 2016 at our institution with baseline and post-RT T1-non contrast MRI images available were processed with NQ brain atrophy report (Coretech labs). Patient, tumor and treatment factors including HC dose-volume (DVH) data (mean, D40%) were correlated with volume changes through Pearson’s correlation coefficients and ordinary least squares regression (OLS) modeling. Pediatric patients (n = 13) with a median age of 12 yrs (range 4-17) at time of treatment were identified for analysis. The most common diagnoses were astrocytoma (31%) and medulloblastoma (23%). 5 patients (38%) underwent craniospinal irradiation (CSI). Median time to post-treatment MRI was 15.7 months (range 8-24). The mean individual HC volume preRT was 4.27 cc. Median HC volume for patients receiving CSI decreased by 0.12 cc. Mean and ipsilateral D40% correlated with decreases in ipsilateral HC volume as measured using NQ (c=0.31, p=0.122, c=0.35 p=0.083, respectively). When controlling for DVH volume on the contralateral side, D40% significantly correlated with ipsilateral NQ volume change pre to post RT (p = 0.002), with an average decrease of 0.011 cc for every 1Gy increase in D40%. Sensitivity analysis excluding patients receiving CSI confirmed D40% was significantly correlated with HC volume change (p=.005). The contralateral HC volume remained stable to slightly larger (mean 0.063 cc increase) for focal RT patients. Although continued growth and development of pediatric brains make it difficult to quantify changes after RT, we demonstrate the potential utility of NQ to identify dose-depended HC volume changes. Furthermore, we found that HC volume decreased over time and significantly correlated with dose parameters, namely an average decrease in 0.011 cc for every 1Gy increase in D40%. Further validation in a larger cohort including correlation with neurocognitive changes is underway.