Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline

Abstract

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT).

Methods and materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits.

Results: In both structures, longitudinal diffusivity (λ(‖)) decreased and perpendicular diffusivity (λ(⊥)) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum λ(⊥) at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in λ(⊥) at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum λ(‖) (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum λ(‖) changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results.

Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

Conflict of interest statement

Conflicts of Interest Notification

The authors declare that no actual or potential conflicts of interest exist.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1

Example of volume locations from patient 10. Left: Axial pre-RT T1- weighted image. Right: Axial pre-RT FA image (white is high anisotropy). Volumes outlined in black. Medial to lateral: Parahippocampal cingulum bundle, hippocampal gray matter, temporal lobe white matter.

Figure 2

A: Changes in mean λ|| over time. B: Changes in mean λ⊥ over time. Solid lines correspond to cingula, dashed lines to temporal lobe. Error bars are ± standard error. *Significant change from pre-RT values.

Figure 2

A: Changes in mean λ|| over time. B: Changes in mean λ⊥ over time. Solid lines correspond to cingula, dashed lines to temporal lobe. Error bars are ± standard error. *Significant change from pre-RT values.

Figure 3

Linear regression plot of percent change in cingula λ|| at 6 weeks to percent change in cingula λ|| at 30 weeks. Each dot represents one patient’s cingula. R = 0.698, p < 0.05.

Figure 4

Linear regression plots of percent change in cingulum λ⊥ to dose at 3 weeks after starting RT. Each dot represents right or left cingulum in one patient. R = 0.493, p < 0.05.

Figure 5

Box plot showing range of percent change in cingula λ⊥ at 3 weeks and 6 weeks in patients with %V12 greater than and less than 50% of cingula volume. Open box is %V12 > 50% (n = 6), shaded box is %V12 < 50% (n = 4). Box represents 25th to 75th percentile, band is median and whiskers are full range of values. Difference at 3 weeks, p < 0.03, at 6 weeks, p < 0.01.

Figure 6

Linear regression plot of percent change in cingula λ|| at 30 weeks to HVLT Total Recall Z-score drop. Each dot represents one patient’s cingula. R = 0.730, p < 0.02.