海马规避放疗中海马损伤的微观影像证据及其对认知的影响

Microimaging evidences of hippocampal injury in radiotherapy avoiding hippocampus and its effects on cognition

目的明确海马规避放疗中海马损伤的影像证据及其与认知的关系。方法本研究采用前瞻性设计。2017年1月至2019年12月在江苏大学附属医院和东南大学附属中大医院随访收集183例接受调强适形放疗(IMRT)的鼻咽癌患者(IMRT放疗组),另收集匹配的30名健康对照组(HC组)。所有受试者均采用蒙特利尔认知评估中文版(MoCA-B)行基线及放疗后6个月的认知评估,并将鼻咽癌放疗患者分为认知损伤组和认知未损伤组。所有受试者行头颅MR扫描,并以T1WI作为纹理特征分析用序列。基于蒙特利尔神经研究所(Montreal Neurological Institute,MNI)脑模板提取个体标准化海马ROI。基于C++和Delphi开发的影像组学计算纹理特征,并运用组内相关系数(ICC)、平均方向、机器学习(随机森林)和自相关矩阵进行特征降维。采用单因素方差分析和广义线性模型进行组间差异性特征比较。运用Pearson相关分析对重要纹理特征与临床资料的关系进行评估。以logistic回归计算纹理特征对认知损伤的预测能力。结果排除19例失访受试者,本研究最终纳入鼻咽癌患者164例作为IMRT组。受试者海马ROI的纹理特征被成功提取并降维。HC组、认知损伤组(56例)及认知未损伤组(108例)间呈现5个差异性特征:方差(Variance)、熵(Entropy)、灰度不均匀性(GlevNonU)、游程不均匀性(RLNonUni)和对比度(Contrast),且后3个呈现IMRT放疗组内差异有统计学意义(GlevNonU,P=0.011;RLNonUni,P<0.001;Contrast,P<0.001)。另外,海马受照剂量与Variance呈正相关(r=0.448,P<0.05),与Entropy呈负相关(r=-0.461,P<0.05)。GlevNonU、RLNonUni及Contrast与MoCA-B评分均呈正相关(r=0.503,P<0.05;r=0.587,P<0.05;r=0.531,P<0.05)。GlevNonU和Contrast是海马规避放疗认知损伤的独立预测因子(OR=0.731,95%CI 0.610~0.857;OR=0.651,95%CI 0.496~0.853)。结论纹理分析结果可作为海马规避放疗中海马损伤的微观影像学证据,且其亦可有效预测认知损伤的发生。

Objective To clarify the evidences of hippocampal injury after radiotherapy avoiding hippocampus and explore its relationships with cognition.Methods A prospective design was adopted in this study.A total of 183 patients with nasopharyngeal carcinoma treated by intensity modulated radiation therapy(IMRT group)and 30 matched healthy control(HC group)were collected in the Affiliated Hospital of Jiangsu University and Southeast University Affiliated Zhongda Hospital from January 2017 to December 2019.All subjects were assessed by Montreal Cognitive Assessment(MoCA-B)at baseline and 6 months after radiotherapy,then the patients with nasopharyngeal carcinoma were divided into cognitive impairment group and non-cognitive impairment group.Subjects were scanned with Siemens 3.0 T MR,and T1WI was used as analysis sequence.The individual standardized hippocampus ROIs were extracted based on Montreal Neurological Institute(MNI)brain template.All texture features were calculated using the Radiomics developed by C++and Delphi,and the intra group correlation coefficients(ICC),average direction,machine learning(random forest)and autocorrelation matrix were used for reducing the features dimension.One-way ANOVA and generalized linear models were used to compare the differences among different groups.Pearson correlations analyses were used to evaluate the relationships between important texture features and clinical data.Logistic regressions were used to calculate the abilities of texture features to predict cognitive impairment.Results After 9 patients who lost follow-up were excluded,a total of 164 patients with nasopharyngeal carcinoma were included as IMRT group.Texture features of ROIs were extracted and dimensionally reduced successfully.Five differences features(Variance,Entropy,GlevNonU,RLNonUni and Contrast)were found among HC group,cognitive impairment group and non-cognitive impairment group,and the last three further showed significant differences within IMRT group(GlevNonU,P=0.011;RLNonUni,P<0.001;Contrast,P<0.001).Hippocampal doses were positively correlated with Variance(r=0.448,P<0.05),and negatively correlated with Entropy(r=-0.461,P<0.05).There was a positive correlation between MoCA-B scores with GlevNonU,RLNonUniand Contrast(r=0.503,P<0.05;r=0.587,P<0.05;r=0.531,P<0.05).GlevNonU and Contrast were independent predictors of cognitive impairment in hippocampal avoidance of radiotherapy(OR=0.731,95%CI 0.610-0.857;OR=0.651,95%CI 0.496-0.853).Conclusion Results of texture analysis could be used as micro imaging evidences of hippocampal injury in radiotherapy avoiding hippocampus,and could also effectively predict the occurrences of cognitive impairment.