Cerebral cortex regions selectively vulnerable to radiation dose-dependent atrophy

Abstract Purpose /Objectives: Neurologic deficits after brain radiotherapy (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 cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. Materials/Methods We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. Study patients had high-resolution, volumetric MRI (T1-weighted; T2 FLAIR) prior to and one year after RT. Semi-automated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region pre-RT and at one year. 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, two 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 two-tailed tests. Results Cortical atrophy was significantly associated with radiation dose in the entorhinal ( p =0.01) and inferior parietal ROIs ( p =0.02). In 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 ≤0.002). 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 develop deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.