Seibert Tyler M, Karunamuni Roshan, Kaifi Samar, Burkeen Jeffrey, Connor Michael, Krishnan Anitha Priya, White Nathan S, Farid Nikdokht, Bartsch Hauke, Murzin Vyacheslav, Nguyen Tanya T, Moiseenko Vitali, Brewer James B, McDonald Carrie R, Dale Anders M, Hattangadi-Gluth Jona A
Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
Department of Radiology, University of California, San Diego, La Jolla, California.
Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):910-918. doi: 10.1016/j.ijrobp.2017.01.005. Epub 2017 Jan 6.
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.
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.
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).
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.
脑部放射治疗（RT）后的神经功能缺损通常涉及高阶认知功能的下降，如注意力和记忆力，而非感觉缺陷或瘫痪。我们试图确定对认知至关重要的皮质区域是否对辐射剂量依赖性萎缩具有选择性易损性。
我们测量了54例接受分次局部脑部放疗的原发性脑肿瘤患者的皮质厚度变化。研究患者在放疗前和放疗后1年接受了高分辨率容积磁共振成像（T1加权；T2液体衰减反转恢复序列，FLAIR）。使用半自动软件对每位患者的大脑皮质解剖区域进行分割。在放疗前和放疗后1年测量每个区域的皮质厚度。测试了两个高阶皮质感兴趣区域（ROI），以确定辐射剂量与皮质变薄之间的关联：内嗅区（记忆）和顶下叶（注意力/记忆）。为作比较，还测试了两个初级皮质ROI：距状裂周围区（视觉）和中央旁小叶（体感/运动）。使用线性混合效应分析测试所有其他皮质区域是否存在显著的辐射剂量依赖性厚度变化。使用双侧检验将统计学显著性设定为α = 0.05。
内嗅区（P = 0.01）和顶下叶ROI（P = 0.02）的皮质萎缩与辐射剂量显著相关。相比之下，在初级皮质ROI（距状裂周围区和中央旁小叶）中未发现显著的辐射剂量依赖性效应。在全皮质分析中，9个区域显示出显著的辐射剂量依赖性萎缩，包括负责记忆、注意力和执行功能的区域（P≤0.002）。
对高阶认知重要的大脑皮质区域可能最易受到辐射相关萎缩的影响。这与临床观察结果一致，即脑部放疗患者在记忆、执行功能和注意力方面存在缺陷。在前瞻性试验中，有必要对区域皮质萎缩与特定领域认知功能进行相关性研究。
