Radiation Dose-Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

Abstract

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy.

Methods and materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05.

Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=-0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean -6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01).

Conclusions: The hippocampus demonstrates radiation dose-dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.

Conflict of interest statement

notification The other authors have no conflicts of interest.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1. Two illustrative cases

Pre-radiotherapy (pre-RT) MRI on left, with color overlay showing automated segmentation of hippocampus in yellow. The text under each hippocampus on the segmented post-RT MRI (right) gives the corresponding percent change in hippocampal volume compared to pre-RT baseline and the mean hippocampus RT dose.

Figure 2

Hippocampal volume change at one year after radiation therapy (RT) compared with mean RT dose to the hippocampus. Each data point represents one hippocampus (left or right). Volume change is reported as percent change relative to pre-RT baseline.