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中国生物医学工程学报  2021, Vol. 40 Issue (5): 521-530    DOI: 10.3969/j.issn.0258-8021.2021.05.02
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脑功能连接模型在机器学习中分类鲁棒性研究——以静息态功能磁共振定位癫痫发作侧为例
杨泽坤1,2, 葛曼玲1,2, 付晓璇1,2, 陈盛华1,2*, 张夫一1,2, 郭志彤1,2, 张志强3*
1(河北工业大学省部共建电工装备可靠性与智能化国家重点实验室,天津 300130)
2(河北工业大学河北省电磁场与电器可靠性重点实验室,天津 300130)
3(南京大学医学院附属金陵医院/东部战区总医院医学影像科,南京 210002)
A Study on the Robustness of Brain Functional Connectivity Model in Machine Learning Classification ——Taking the Resting-State Functional Magnetic Resonance Imaging to Localize Paroxysmal Side in TLE as Example
Yang Zekun1,2, Ge Manling1,2, Fu Xiaoxuan1,2 , Chen Shenghua1,2* , Zhang Fuyi1,2 , Guo Zhitong1,2, Zhang Zhiqiang3*
1(State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China)
2(Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300130, China)
3(Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine/ General Hospital of Eastern Theater, Nanjing 210002, China)
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摘要 机器学习能促进静息态功能磁共振成像(rfMRI)在癫痫中应用,尽管Pearson相关性的传统功能连接(FC)模型作为成像算法有较多报道,但其分类鲁棒性却少有研究。提出特异于健康人的癫痫患者FC指数模型,与FC在有监督机器学习分类敏感性和稳定性上进行比较, 以期为提取癫痫患者功能影像学标记提供新算法。搜集20名结构像标记为海马阳性的内侧颞叶癫痫患者(各10名纳入左侧、右侧2组)和142名来自连接组学且与患者相同年龄段健康人的rfMRI数据;以健康人群为参照,构建个体患者FC特异性指数模型,为每个脑区功能打分;通过ROC敏感性分析曲线和曲线下面积(AUC)提取指数模型,对发作侧敏感脑区获得功能影像标记;以其指数作为特征向量,分别输入至概率神经网络和支持向量机,对患者发作侧分类;10次随机交叉验证分析稳定性,再分别对敏感脑区之间和患者之间的特征向量做线性相关性分析,以探求影响稳定性的内在原因。最后,用FC代替指数模型做同上处理,并比较两种功能连接模型的分类稳定性。结果显示,以FC为特征向量的AUC为0.76,而特异性指数的特征向量AUC为0.84,指数模型的分类敏感性高于FC。另外,FC的分类精度在25%~100%之间强烈波动,方差高达25.99%,且特征向量平均相关系数为0.67,相关性较强;而指数模型则在75%~100%之间较小波动,方差低至7.10%,且特征向量平均相关系数为0.28,相关性较小。在机器学习癫痫定侧中,静息态功能连接特异性指数模型表现出较强的分类鲁棒性,远优于传统模型,特征向量相关性较大可能是影响后者稳定性的主要原因。
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杨泽坤
葛曼玲
付晓璇
陈盛华
张夫一
郭志彤
张志强
关键词 功能连接特异性Pearson相关性静息态功能磁共振成像有监督机器学习癫痫发作侧定位    
Abstract:Currently, machine learning has promoted the application of resting-state functional magnetic resonance imaging (rfMRI) in epilepsy, where the functional connectivity model of Pearson correlation (FC) has been widely applied as a traditional imaging algorithm. However, the classification stability of functional connectivity model is rarely studied in the machine learning. To address this issue, a FC-based index model specific to the healthy people was proposed in this work, the classification stability was studied by a random cross validation in the supervised machine learning models, and compared to the results of FC, aiming to provide a new algorithm in extracting FC features input into machine learning. The rfMRI data of a total of twenty patients of medial temporal lobe epilepsy with a positive indicator of hippocampus on structure MRI (equally involved in a group of left side and a group of right side), and a total of 142 healthy people from a connectome including Southwest Adult Lifespan Dataset (SALD) in the same age group were collected. A rfMRI FC-based index model was built up, specific to the healthy people, referred as FC-based specificity index model. Thus, every FC of each brain area in an individual patient could be scored, and the brain areas sensitive to paroxysmal side could be extracted by the ROC curve. The sensitivity analysis curve was taken as the functional bio-markers, whose indexes were assigned as the feature vectors to input into the supervised machine learning models such as probabilistic neural network (PNN) and support vector machine (SVM) to classify paroxysmal side. Additionally, the classification stability was validated by a random cross validation (10 times), and the linear correlation of feature vectors between sensitive brain areas and between patients were estimated to evaluate their interdependence, aiming to find out the underlying cause to affect the classification stability. Finally, the same procedures as above were fulfilled by the FC model instead of FC-based specificity index model, and the classification stability was compared. The AUC of the feature vector of FC was 0.76, and the feature vector of specificity index was 0.84. The classification sensitivity of the FC-based specificity index model was higher than that of FC. In addition, the classification accuracy of FC fluctuated strongly between 25%~100%, the variance was as high as 25.99%, and the average correlation coefficient of the feature vector was 0.67, which had a strong correlation; while the accuracy of the exponential model was stable at 75%~100%. The variance was as low as 7.10%, and the average correlation coefficient of the feature vector was 0.28, which was relatively small. When paroxysmal side of medial temporal lobe epilepsy was subjected to the resting-state functional magnetic resonance imaging in the machine learning, the proposed FC-based specificity index model performed robustly, much better than the traditional FC model such as Pearson correlation, and the larger correlation between the feature vectors formed by the traditional FC model might be the main cause that led to the low classification stability.
Key wordsfunctional connectivity specificity    Pearson correlation    resting-state fMRI    supervised machine learning    localization of paroxysmal side in epilepsy
收稿日期: 2020-11-20     
PACS:  R318  
基金资助:河北省研究生创新项目(CXZZSS2021034);国家自然科学基金(81871345);河北省省级科技计划项目(E2019202019)
通讯作者: *E-mail: chenshenghua@hebut.edu.cn; zhangzq2001@126.com   
引用本文:   
杨泽坤, 葛曼玲, 付晓璇, 陈盛华, 张夫一, 郭志彤, 张志强. 脑功能连接模型在机器学习中分类鲁棒性研究——以静息态功能磁共振定位癫痫发作侧为例[J]. 中国生物医学工程学报, 2021, 40(5): 521-530.
Yang Zekun, Ge Manling, Fu Xiaoxuan, Chen Shenghua, Zhang Fuyi, Guo Zhitong, Zhang Zhiqiang. A Study on the Robustness of Brain Functional Connectivity Model in Machine Learning Classification ——Taking the Resting-State Functional Magnetic Resonance Imaging to Localize Paroxysmal Side in TLE as Example. Chinese Journal of Biomedical Engineering, 2021, 40(5): 521-530.
链接本文:  
http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021.2021.05.02     或     http://cjbme.csbme.org/CN/Y2021/V40/I5/521
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