乳腺癌患者化疗早期大脑皮层表面形态学改变和癌症相关疲劳变化的关系:基于表面形态测量方法

Surface-based morphological study on the relationship between cortical surface morphological changes and cancer-related fatigue changes in early chemotherapy for breast cancer

目的研究乳腺癌患者化疗早期大脑皮层表面形态改变及其与癌症相关疲劳(cancer-related fatigue,CRF)变化的关系。材料与方法选取25例首诊女性乳腺癌患者,分别在手术后化疗前(化疗开始前一周内)、化疗期间(化疗第二个周期结束后两周内)进行简易疲乏量表(Brief Fatigue Inventory,BFI)、汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)和汉密尔顿焦虑量表(Hamilton Anxiety Scale,HAMA)等神经心理学测试和颅脑磁共振3D-T1加权数据采集。同期招募年龄匹配的健康女性作为对照组,并在匹配的时间间隔内使用同样的评估方式进行临床资料和磁共振数据收集。基于表面的形态学方法(surface-based morphometry,SBM),采用统计参数映射分析12(statistical parametric mapping,SPM 12)软件包中的计算解剖工具箱12(computational anatomy toolbox,CAT 12)对所有受试者进行大脑皮层表面形态学分析,采用SPSS 26.0分析乳腺癌患者化疗期间皮层表面形态改变的脑区与CRF纵向变化之间的相关性。结果与化疗前相比,乳腺癌患者在化疗早期的CRF、抑郁、焦虑测量评分差异有统计学意义(P<0.05);化疗期间乳腺癌患者皮层表面形态的皮层厚度、沟深、分形维数、皮质褶皱指数参数值较化疗前发生了改变,差异有统计学意义(P<0.05):顶叶(双侧楔前叶、右侧缘上回、右侧中央后回)、枕叶(双侧楔叶)的皮层厚度减少,顶叶(双侧顶下小叶、右侧缘上回及顶上小叶)、颞叶(右侧梭状回、颞上回及颞下回)、枕叶(双侧枕外侧回、右侧楔叶、右侧距状旁回)的沟深减少,左侧枕叶(枕外侧回)、右侧额叶(额上回、前中额叶及额下回)、右侧顶叶(缘上回及顶下小叶)的分形维数减少,左侧枕叶(枕外侧回及楔叶)、右侧顶叶(缘上回、顶上小叶及顶下小叶)、右侧颞叶(颞中回、颞下回及颞上回后部)的皮层褶皱指数增大;与化疗前相比,化疗早期右前中额叶分形维数的改变与CRF的纵向变化呈负相关(r=-0.628,P=0.001)。结论乳腺癌患者的皮层表面形态在化疗早期即可发生改变,并与CRF的变化相关。

Objective:To study the early changes in cortical surface morphology in breast cancer patients in the early stage of chemotherapy and its relationship with cancer-related fatigue(CRF).Materials and Methods:Twenty-five first-diagnosed female breast cancer patients were taken for neuropsychological tests such as Brief Fatigue Inventory(BFI),Hamilton Depression Scale(HAMD),and Hamilton Anxiety Scale(HAMA)and cranial magnetic resonance 3D-T1-weighted data acquisition before(within one week before the start of chemotherapy)and during(within two weeks of the end of the second cycle of chemotherapy)postoperative chemotherapy,respectively.Age-matched healthy women were recruited as a control group during the same period,and clinical information and magnetic resonance data were collected using the same assessed approach during the matched time intervals.Surface-based morphometry(SBM)was used to analyze the surface morphology of the cerebral cortex of all subjects using the computational anatomy toolbox 12(CAT 12)in the statistical parametric mapping 12(SPM 12)software,and SPSS 26.0 was used to analyze the correlation between brain areas with altered surface morphology of the cortex and longitudinal changes in CRF during chemotherapy in breast cancer patients.Results:Compared with the pre-chemotherapy period,the differences in CRF,depression,and anxiety measurement scores of breast cancer patients in the early stage of chemotherapy were statistically significant(P<0.05).The values of cortical thickness,sulcal depth,fractal dimension,and gyrification index parameter of cortical surface morphology of breast cancer patients during chemotherapy changed compared with that of the pre-chemotherapy period.The differences were statistically significant(P<0.05):there was a reduction in cortical thickness in the parietal lobes(bilateral precuneus,right supramarginal,right postcentral)and occipital lobes(bilateral cuneus),a reduction in sulcus depth in the parietal lobes(bilateral inferiorparietal,right supramarginal and superiorparietal),the temporal lobes(right fusiform,superiortemporal and inferiortemporal),the occipital lobes(bilateral lateraloccipital,right cuneus,right pericalcarine),and a reduction in the number of fractal dimensions in the right frontal lobes(superiorfrontal,rostralmiddlefrontal and parsorbitalis),the right parietal lobes(supramarginal and inferiorparietal),and the left occipital lobes(lateraloccipital);The brain regions with increased parameter values were increased gyrification index in the left occipital lobe(lateraloccipital and cuneus),right parietal lobe(supramarginal,superiorparietal,and inferiorparietal),and right temporal lobe(middletemporal,inferiortemporal,and bankssts).Changes in the fractal dimension of the right rostralmiddlefrontal in the early phase of chemotherapy were negatively correlated with longitudinal changes in CRF compared with the pre-chemotherapy phase(r=-0.628,P=0.001).Conclusions:Cortical surface morphology in breast cancer patients can undergo early changes during chemotherapy and associated with changes in CRF.