Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy

Abstract

Purpose and objectives: Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy.

Methods and materials: We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests.

Results: Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002).

Conclusions: Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.

Figure 1

(A) Cortical regions from the Desikan-Killiany atlas available in the FreeSurfer neuroimaging software suite. Regions are displayed on the FreeSurfer average brain for illustration, but statistical analyses were carried out using the corresponding regions delineated in the native MRI space of each patient. Average radiation dose and average cortical thickness change were calculated for each region. (B) Cortical regions with significant radiation dose-dependent cortical atrophy in linear mixed-effects model. FreeSurfer average brain surface shown in gray (light gray for gyrus, dark gray for sulcus). Regions statistically significant after correction for multiple comparisons are colored. Only the left hemisphere is shown for convenience, but statistical tests included bilateral observations.

Figure 2

Cortical thickness change vs. radiation dose for four regions of interest. Thickness change is the mean change from pre-radiation baseline to approximately one year after start of radiation therapy. Radiation dose is the mean dose to that region of cortex. Stated (two-sided) p-values are for the hypothesis that thickness decreases with increasing radiation dose. Regression slopes (±SE): entorhinal −7.1 ± 2.7 μm/Gy; inferior parietal −2.0 ± 0.8 μm/Gy; pericalcarine −0.2 ± 0.9 μm/Gy; paracentral 0.3 ± 0.8 μm/Gy.