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.

Effects of long-term and brain-wide colonization of peripheral bone marrow-derived myeloid cells in the CNS

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“…Rather, these new data indicate a cellular response that involves different brain regions at different degrees and rates of changes along the varying post-radiation time points. This differential post-radiation timing is likely due to the intrinsic radiosensitivity to γ-rays in each speci c cerebral region (based, for example, on their intrinsic genetically-determined metabolic rate) as well as possibly related to the total radiation dose administered [39][40][41] . These differential radiosensitivity-related aspects across different brain regions as well as their possible controlled modulation could lead to precise and effective neuroanatomical-based brain radiation protocols selectively tuned for a speci c region of the brain, or a group of disease-related neuroanatomical regions, in the context of a speci c brain disease and local brain tissue vulnerability.…”

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“…This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Cerebral irradiation may cause decline in cognitive function, as described in cohorts of patients receiving radiotherapy for intracranial tumours [10][11][12][13][14][15][16][17][18] and whole brain irradiation [19][20][21]. Different domains of cognitive functions are potentially affected, namely processing speed, attention, working memory, learning and memory, verbal fluency and executive function.…”