Statistical inversion for medical X-ray tomography with few radiographs II Application to d
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分类号:B845.4单位代码:10346密级:学号:2012110046硕士学位论文中文论文题目:麻醉状态下脑活动的无尺度属性:一项探索性的功能磁共振研究英文论文题目:Global Reduction of Scale-free Brain Activityand Its Dissociation from Temporal Variabilityin Anesthesia: An Exploratory fMRI Study申请人姓名:张剑锋指导教师:翁旭初合作导师:Georg Northoff专业名称:心理学研究方向:临床认知神经科学所在学院:教育学院麻醉状态下脑活动的无尺度属性:一项探索性的功能磁共振研究论文作者签名:指导教师签名:论文评阅人1:评阅人2:评阅人3:评阅人4:评阅人5:答辩委员会主席:委员1:委员2:委员3:委员4:委员5:答辩日期:杭州师范大学研究生学位论文独创性声明本人声明所呈交的学位论文是本人在导师指导下进行的研究工作及取得的研究成果。
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Value analysis of DCE-MRI-AI in predicting the curative effect of neoadjuvant chemotherapy for breast cancer/Gong Junfeng, Wang Yongjie, Ding Yu, Xue Zhou, Shen GaoyaoDepartment of Medical Imaging, Chongming Branch of Shanghai Xinhua Hospital, Shanghai 202150, China Corresponding author: [Abstract] Objective: T o investigate the value of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) based on artificial intelligence (AI) technique in predicting the curative effect of neoadjuvant chemotherapy for breast cancer . Methods: A total of 89 patients with breast cancer received neoadjuvant chemotherapy in Chongming Branch of Shanghai Xinhua Hospital from January 2018 to December 2020 were collected, and they were divided into an effectiveness group (36 cases) and an ineffectiveness group (53 cases) according to the treatment effect. DCE-MRI examinations were performed before neoadjuvant chemotherapy and after the end of the fourth course of treatment, and a time-signal intensity curves were drawn. V olume transfer constant (K trans ), rate parameter (K ep ) and extravascular space volume ratio (V e ) were measured. The original DCE-MRI image was expanded, and the region of interest containing the lesion was extracted, and the deep convolutional neural network was used to carry out convolutional operation, and the classification model was obtained through training set. The receiver operating characteristic (ROC) curve was drawn, and the model with the highest value of area under curve (AUC) of validation set was selected as the terminal model to evaluate the model performance of the test set. Results: After chemotherapy, the results of DCE-MRI showed that K trans (0.67±0.15) and K ep (1.22±0.24) in the effectiveness group were significantly lower than those in the ineffectiveness group, while ΔK trans (1.51±0.18) and ΔK ep (2.31±0.26) were significantly higher than those in the ineffectiveness group, and the differences were statistically significant (t =23.072, 20.016, P <0.05). The AUC values of ΔK trans , ΔK ep and ΔV e in predicting the curative effect of neoadjuvant chemotherapy for breast cancer were respectively 0.814, 0.839 and 0.432. The sensitivity , specificity and AUC value of the combined detection of them were respectively 89.93%, 83.48% and 0.845, which predictive value was higher than that of single detection. The DCE-MRI-AI model has higher predictive efficiency for the curative effect of neoadjuvant chemotherapy for breast cancer, and the AUC values of training set, verification set and test set of that were respectively 0.897, 0.869 and 0.859. In the training set and verification set, there was statistical difference between DCE-MRI-AI model and DCE-MRI model in predicting efficiency for the curative effect of neoadjuvant chemotherapy for breast cancer (Z training set =2.435, Z verification set =2.147, P <0.05). Conclusion: The application of AI technique in DCE-MRI is helpful to improve the predictive efficiency for neoadjuvant chemotherapy for breast cancer , and provide reliable data for the treatment and prognostic assessment, which has clinical application value.[Key words] Breast cancer; Neoadjuvant chemotherapy; Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); Artificial intelligence (AI); Convolutional neural network: Evaluation of curative effectFund program: Chongming District, Shanghai Sustainable Development of Science and T echnology Innovation Action Plan (CKY2021-10)[摘要] 目的:探讨基于人工智能(AI)技术动态对比增强磁共振成像(DCE-MRI)预测乳腺癌新辅助化疗疗效的价值。
Advances in Clinical Medicine 临床医学进展, 2023, 13(10), 15864-15869Published Online October 2023 in Hans. https:///journal/acmhttps:///10.12677/acm.2023.13102217CBCT X射线图像引导技术在直肠癌IMRT放疗中的应用刘平1,2,李玉锋2,陈成成3,赵涛4*1青岛大学医学部基础医学院,山东青岛2日照市人民医院放疗科,山东日照3日照市人民医院放射科,山东日照4日照市人民医院中心实验室,山东日照收稿日期:2023年9月11日;录用日期:2023年10月5日;发布日期:2023年10月12日摘要目的:探讨锥体束计算机断层扫描(CBCT) X射线图像引导技术在直肠癌调强放疗(IMRT)中的作用。
方法:回顾性分析2022年1月至2023年6月于日照市人民医院放疗科行IMRT放疗的15例直肠癌患者的临床资料。
病人治疗摆位完成后采用CBCT X射线图像引导获得扫描图像,与数字重建放射影像(DRR)进行匹配,得到3个方向的平移摆位误差和3个方向的旋转摆位误差,并进行统计分析,最后得出锥体束计算机断层扫描(CBCT) X射线图像引导技术在直肠癌调强放疗(IMRT)中的作用。
结果:15例患者的位置验证均采用CBCT扫描,共获取375组X射线图像,分别与治疗计划DRR进行图像配准然后得出每次治疗的摆位误差。
平移方向上Y (头、脚)方向的平移摆位误差最大,摆位误差为(2.245 ± 0.709) cm;X (左、右)方向次之,摆位误差为(0.623 ± 0.203) cm;Z (胸、背)方向最小,摆位误差为(0.492 ± 0.163) cm。
旋转方向上RTN (左、右)方向的旋转摆位误差最大,摆位误差为(4.333 ± 1.121)˚;ROLL (胸、背)方向次之,摆位误差为(3.94 ±0.809)˚;PITCH (头、脚)方向最小,摆位误差为(2.94 ± 1.195)˚。
第42卷㊀第5期2023年㊀10月北京生物医学工程BeijingBiomedicalEngineeringVol 42㊀No 5October㊀2023㊃论㊀著㊃基于动态Hurst指数的人脑老化复杂度分析倪黄晶1,2㊀李新林1㊀秦姣龙3摘㊀要㊀目的研究健康成人在不同年龄段的功能特点可以更好地理解人脑的老化过程,Hurst指数可以测量静息态功能磁共振成像时间序列的复杂度㊂既往对大脑复杂度随年龄变化的研究,还存在样本量小㊁未考虑复杂度的动态变化等局限性㊂因而有必要在大样本被试上通过刻画复杂度的动态变化特性,来研究人脑随年龄变化的规律㊂方法选择19 80岁的458名健康成人静息态功能磁共振成像数据,划分为青年组(n=213)㊁中年组(n=142)和老年组(n=103),通过滑窗法来计算动态Hurst指数,并进一步提取其平均值㊁标准差和变异系数特征来描述人脑的动态复杂度水平和波动程度,最后通过统计分析来评判不同年龄组被试的复杂度差异㊂结果在平均值特征上,双侧颞上回㊁双侧岛回㊁右侧扣带回和双侧腹中侧枕叶皮层的复杂度随年龄增长而降低,而双侧眶回和左侧楔前叶的复杂度则随年龄的增长而呈现出倒U形变化;在标准差和变异系数特征上,老年组在右侧楔前叶的动态复杂度显著大于青年组和中年组㊂结论人脑老化过程中全脑复杂度动态变化模式并不一致,且在不同的年龄段上,局部脑区存在不同的组间统计显著差异模式㊂该结果可以为研究者理解正常老化的功能机制提供帮助㊂关键词㊀动态Hurst指数;脑老化;静息态功能磁共振成像;时间序列;复杂度DOI:10 3969/j.issn.1002-3208 2023 05 001.中图分类号㊀R318 04㊀㊀文献标志码㊀A㊀㊀文章编号㊀1002-3208(2023)05-0441-07本文著录格式㊀倪黄晶,李新林,秦姣龙.基于动态Hurst指数的人脑老化复杂度分析[J].北京生物医学工程,2023,42(5):441-447.NIHuangjing,LIXinlin,QINJiaolong.ComplexityanalysisofhumanbrainagingusingdynamicHurstexponent[J].BeijingBiomedicalEngineering,2023,42(5):441-447.ComplexityanalysisofhumanbrainagingusingdynamicHurstexponentNIHuangjing1,2,LIXinlin1,QINJiaolong31㊀SchoolofGeographicandBiologicInformation,NanjingUniversityofPostsandTelecommunications,Nanjing㊀210003;2㊀SmartHealthBigDataAnalysisandLocationServicesEngineeringLabofJiangsuProvince,Nanjing㊀210003;3㊀SchoolofComputerScienceandEngineering,NanjingUniversityofScienceandTechnology,Nanjing㊀210094Correspondingauthor:QINJiaolong(E⁃mail:jiaolongq@njust edu cn)ʌAbstractɔ㊀ObjectiveItcanbetterhelptounderstandtheagingprocessofhumanbrainbystudyingthefunctionalcharacteristicsofhealthyadultsatdifferentages.Hurstexponentcanmeasurethecomplexityofresting⁃statefunctionalmagneticresonanceimaging(rs⁃fMRI)timeseries.Previousstudiesonthechangeofbraincomplexitywithagestillhavesomelimitations,suchassmallsamplesizeandignoringthedynamicchangeofcomplexity.Therefore,itisnecessarytostudythechangingcharacteristicsoftheagingbrainbymeasuringthedynamicchangesofcomplexityinalargesamplesize.MethodsByusingthers⁃fMRIdatafrom458healthyadultsaged19to80,wefirstlydividedthesubjectsintotheyounggroup(n=213),themiddle⁃agedgroup(n=142)andtheelderlygroup(n=103).ThedynamicHurstexponentwasthencalculatedbytheslidingwindowmethod,anditsmeanvalue,standarddeviationandcoefficientofvariationwerefurtherextractedtodescribethelevelofdynamiccomplexityandfluctuationdegreeofthehumanbrain.Finally,thecomplexitydifferencesofgroupswithdifferentageswereanalyzedbystatisticalanalysis.ResultsForthemeanvalue,thecomplexityofbilateralsuperiortemporalgyrus,bilateralinsulargyrus,rightcingulategyrusandbilateralventralmiddleoccipitalcortexcoulddecreasewithage,whilethecomplexityofbilateralorbitalgyrusandleftprecuneusshowedaninvertedU⁃shapedchangewithage.Forthestandarddeviationandcoefficientofvariation,thedynamiccomplexityoftherightprecuneusintheelderlygroupwassignificantlyhigherthanthatintheyounggroupandmiddle⁃agedgroup.ConclusionsDuringthenormalagingofthehumanbrain,thedynamicchangepatternsofcomplexityinthewholebrainarenotconsistent,andtherearedifferentstatisticallysignificantdifferencepatternsamongdifferentagegroupsincertainlocalbrainregions.Ourresultscanhelptoimprovetheunderstandingofthefunctionalmechanismofbrainaging.ʌKeywordsɔ㊀dynamicHurstexponent;brainaging;restingstatefunctionalmagneticresonanceimaging;timeseries;complexity基金项目:江苏省自然科学基金青年项目(BK20190736)㊁国家自然科学基金青年项目(81701346,61603198)㊁南京邮电大学引进人才科研启动基金项目(NY218138)资助作者单位:1㊀南京邮电大学地理与生物信息学院(南京㊀210003)2㊀江苏省智慧健康大数据分析与位置服务工程实验室(南京㊀210003)3㊀南京理工大学计算机科学与工程学院(南京㊀210094)通信作者:秦姣龙㊂E⁃mail:jiaolongq@njust edu cn0㊀引言随着老年人口的日益增加,越来越多的研究开始关注健康生命周期中与年龄相关的认知变化规律[1]㊂人脑是一个极其复杂的动态系统,其结构和功能十分复杂,随着年龄的增长,脑组织的细胞㊁形态及功能都会发生一定的变化,可能会影响人的协调能力㊁语言能力㊁情绪控制能力㊁认知能力等机体功能[2]㊂深入理解正常老化过程中脑功能的变化规律,具有极为重要的意义㊂静息态功能磁共振成像(resting⁃statefunctionalmagneticresonanceimaging,rs⁃fMRI)技术通过非侵入性地测量人脑血氧水平依赖信号从而间接获取脑神经活动的相关信息,已成为研究人脑功能变化规律的重要手段㊂既往研究表明,随着年龄的增长,人脑复杂度也会随之降低[3]㊂在先前的研究中,常用样本熵㊁模糊近似熵和多尺度熵等来进行人脑功能复杂度的分析㊂例如,Sokunbi等[4]基于正常人脑rs⁃fMRI信号的复杂度分析,发现全脑模糊近似熵均值与年龄呈显著负相关,且额叶㊁顶叶㊁边缘叶㊁颞叶和小脑顶叶的模糊近似熵也与年龄呈显著负相关㊂Yang等[3]使用多尺度熵比较了年轻人和老年人rs⁃fMRI信号的复杂度,发现老年组rs⁃fMRI信号的多尺度熵在左侧嗅皮质㊁右侧后扣带回㊁右侧海马㊁右侧海马旁回㊁左侧枕上回左侧尾状核和左侧丘脑区域比年轻组显著降低㊂Cieri等[5]认为在正常条件下大脑系统的复杂度随外部环境的复杂性的增加而增加㊂这些研究表明,人脑老化过程中伴随着复杂度的改变,通过测量复杂度特性,可以较好地揭示出人脑的正常老化特征㊂然而由于熵值分析对于数据长度有要求,这使得熵值分析在只有数百个时间点的rs⁃fMRI信号动态变化分析中受到局限㊂Hurst指数可用于测定时间序列中的长短程相关性,它对于时间序列长度的要求相对宽松,且具有可解释性强㊁适用性广的优点㊂当前,其在健康老化和脑疾病研究[6-7]中已得到良好的应用,如轻度认知障碍[8]㊁精神分裂症[9]㊁自闭症[10]㊁焦虑症[11]以及抑郁症[12]等㊂然而上述研究所用的样本量普遍为30 120,相对小的样本量会使所得结果更容易受到个体差异的影响㊂更重要的是,上述研究大多基于序列中的所有时间点进行静态复杂度分析,而忽视了fMRI信号内在的动态变化特性㊂最近的研究表明,rs⁃fMRI信号具有动态变化特性[13]㊂因而,通过分析大样本被试脑内复杂度的动态变化特性,有助于更深入地刻画人脑随年龄变化的内在规律㊂鉴于此,本研究基于滑窗法来计算动态Hurst指数,以研究不同年龄被试rs⁃fMRI信号复杂度的㊃244㊃北京生物医学工程㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀第42卷动态变化情况㊂通过进一步提取其平均值㊁标准差和变异系数特征来分析不同脑区rs⁃fMRI信号动态复杂度的水平和波动程度的差异㊂最后通过对比不同年龄组被试间的统计差异,来探究人脑老化过程中全脑的复杂度动态变化模式,以此推进对正常脑老化功能机制的理解㊂1㊀材料和方法1 1㊀实验数据本研究采用的数据集是来自西南大学的成人功能磁共振成像数据集[14]㊂该数据集包含494名健康成年人(187名男性㊁307名女性)的T1加权图像数据和rs⁃fMRI数据,被试年龄为19 80岁㊂在数据预处理中,共有36名被试(8名男性和28名女性)因头动幅度较大而被排除㊂最终,共有458人(179名男性和279名女性)参与本研究㊂该数据集得到了西南大学脑成像中心研究伦理委员会的批准,数据收集也获得了所有参与者的书面知情同意㊂实验中,要求被试静躺㊁闭眼㊁不进行特定思考且不能入睡㊂其中,rs⁃fMRI扫描参数如下:repetitiontime=2000ms;echotime=30ms;flipangle=90ʎ;fieldofview=220mmˑ220mm;thickness=3mm;slicegap=1mm;voxelsize=3 4mmˑ3 4mmˑ4mm;timepoints=242㊂T1结构像扫描参数如下:repetitiontime=1900ms;echotime=2 52ms;inversiontime=900ms;FA=90ʎ;resolutionmatrix=256ˑ256;slice=176;thickness=1 0mm;voxelsize=1mmˑ1mmˑ1mm㊂随后,本研究将所有被试分为青年组㊁中年组和老年组,各组被试的年龄跨度和性别分布情况如表1所示㊂表1㊀本研究所用被试的人口学信息Table1㊀Demographicinformationofsubjectsusedinthisstudy年龄组年龄跨度总人数男性女性青年组19 4421385128中年组45 591424795老年组60 8010347561 2㊀数据预处理和时间序列提取本研究采用DPABI工具箱[15-16]进行rs⁃fMRI数据的预处理㊂预处理步骤主要包括:(1)去除前10个时间点;(2)层间时基校正;(3)头动校正,排除掉平均帧间位移超过0 2的被试;(4)去除协变量(包括线性漂移㊁白质和脑脊液信号);(5)使用Friston24模型回归头动的影响;(6)空间标准化;(7)使用4mm的高斯平滑核进行空间平滑㊂随后,基于脑网络组图谱[17],提取了所有被试的全脑时间序列㊂1 3㊀动态Hurst指数的计算本研究采用重标极差分析法[18]计算Hurst指数,其算法原理如下:(1)给定一个长度为L的时间序列X=(x1,x2, ,xL),将其分割为若干等长的离散序列㊂Xmk=(x(k-1)m+1,x(k-1)m+2, ,xkm)(1)㊀㊀式中:m=1,2,3, ,M为每个区间离散序列的长度;M为分割后离散序列的最大长度;k=1,2,3, ,int(L/m)㊂(2)计算每个区间内的极差和标准差㊂极差计算公式为:Rk,m=max mi(x(k-1)m+i-xk)-min mi(x(k-1)m+i-xk)(2)标准差计算公式为:Sk,m=1m mi(x(k-1)m+i-xk)2(3)㊀㊀式中:xk为每个区间的平均值㊂(3)计算重标极差均值RSæèçöø÷m=1int(L/m) int(L/m)k=1Rk,mSk,m(4)㊀㊀(4)变化不同的m,计算出对应的重标极差值RSæèçöø÷m对lnm,lnRSæèçöø÷mæèçöø÷进行最小二乘拟合出的直线斜率即为时间序列X的Hurst指数H㊂H的范围在0 1之间,H>0 5表示时间序列的持续长程记忆,H<0 5表示反相关时间序列,H=0 5则表示随机白噪声时间序列[11]㊂为了探究时间序列复杂度的动态变化特性,本研究进一步采用滑动时间窗将时间序列分割为若干个窗口,并在每个滑动窗内采用上述重标极差分析算法计算Hurst指数㊂在滑动时间窗使用中,需要㊃344㊃第5期㊀㊀㊀㊀㊀㊀倪黄晶,等:基于动态Hurst指数的人脑老化复杂度分析预设窗长和滑动步长㊂依据文献[19]的建议,当时间序列长度超过64个点时,Hurst指数的计算结果是可靠的,因此本研究设置窗口长度为64个时间点㊁滑动步长为1个时间点㊂据此,每个被试每个脑区的时间序列共包括169(即232-64+1)个滑动窗㊂1 4㊀基于动态Hurst指数波动序列的统计分析在获取的动态Hurst波动序列基础上,本研究进一步计算了每条波动序列的平均值㊁标准差和变异系数,来衡量动态序列的波动特性,并基于这些动态指标来进行组间统计比较㊂具体说来,本研究使用DPABI工具箱内置的统计分析功能模块[20],对青年组㊁中年组和老年组三组受试者的动态Hurst波动序列指标进行单因素方差分析,并将性别因素作为协变量,使用基于无阈值聚类增强(threshold⁃freeclusterenhancement,TFCE)的置换检验方法[21]进行多重比较校正㊂置换检验次数设为1000,校正后的阈值设为0 05㊂在得到具有显著差异的脑区后,接着进行事后检验分析,以探究两两之间具有显著差异的群组㊂2㊀实验结果2 1㊀基于动态Hurst波动序列平均值的统计结果基于动态Hurst指数的平均值对三组受试者做单因素方差分析,并使用TFCE方法进行多重比较校正(P<0 05),结果显示青年组㊁中年组和老年组三组之间在双侧眶回㊁双侧颞上回㊁左侧楔前叶㊁双侧岛回㊁右侧扣带回㊁双侧腹中侧枕叶皮质有显著差异,如图1所示㊂在事后检验分析中,基于上述有显著差异的脑区,本研究进一步对青年组㊁中年组和老年组的动态Hurst指数平均值两两之间进行双样本t检验,并使用基于TFCE的置换检验方法进行多重比较校正,结果如图2所示㊂从图2中可以发现,青年组和中年组动态Hurst指数平均值有显著差异的脑区主要位于双侧眶回㊁双侧颞上回㊁左侧楔前叶和右侧扣带回,其中在双侧颞上回和右侧扣带回区域,青年组的动态Hurst指数平均值显著大于中年组,而在双侧眶回和左侧楔前叶区域,青年组的动态Hurst指数平均值显著小于中年组㊂中年组和老年组动态Hurst指数平均值有显著差异的脑区主要位于双侧颞上回和右侧岛回,且在这些区域中,中年组的动态Hurst指数平均图1㊀青年㊁中年㊁老年三组被试之间动态Hurst指数平均值有显著差异的脑区分布图Figure1㊀Brainareadistributionmapwithsignificantdifferencesamongtheyoung,middle⁃agedandelderlygroupsusingthemeanvalueofdynamicHurst值均大于老年组㊂此外,青年组和老年组动态Hurst指数平均值存在显著差异的脑区位于双侧颞上回㊁左侧楔前叶㊁双侧岛回㊁右侧扣带回和双侧腹中侧枕叶皮质㊂其中在双侧颞上回㊁双侧岛回㊁右侧扣带回和双侧腹中侧枕叶皮质区域,青年组的动态Hurst指数平均值均显著大于老年组;而只有在左侧楔前叶区域,青年组的动态Hurst指数平均值则显著小于老年组㊂2 2㊀基于动态Hurst波动序列标准差的统计结果基于动态Hurst指数的标准差对3组受试者进行单因素方差分析,并使用基于TFCE的置换检验方法进行多重比较校正后,发现青年组㊁中年组和老年组之间存在显著差异的脑区为右侧楔前叶(F=8 24,TFCE校正P=0 0266),其脑区分布如图3所示㊂事后检验分析结果显示,青年组和中年组之间无显著差异,而中年组和老年组在右侧楔前叶存在显著差异(t=-3 84,TFCE校正P=0 002),青年组和老年组也在该区域存在显著差异(t=-3 35,TFCE校正P=0 001)㊂2 3㊀基于动态Hurst波动序列变异系数的统计结果基于动态Hurst指数的变异系数对3组受试者做单因素方差分析,使用基于TFCE的置换检验方法进行多重比较校正,结果显示青年组㊁中年组和老年组3组之间存在显著差异的脑区位于右侧楔前叶㊃444㊃北京生物医学工程㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀第42卷青年组㊁中年组和老年组的动态Hurst指数平均值分别以绿色㊁蓝色和黄色柱状图表示,柱状图顶端的误差棒表示各群组上动态Hurst指数平均值的标准误㊂事后检验分析中,青年组与中年组之间存在显著差异的脑区在该图顶端使用绿色跨度线囊括,而中年组和老年组之间㊁青年组和老年组之间均以蓝色和黄色跨度线囊括㊂P<0 05以 ∗ 表示,P<0 01以 ∗∗ 表示,P<0 001以 ∗∗∗ 表示㊂此外,横坐标中具有显著差异的脑区分别属于不同的脑回区域,该图中以不同颜色的底纹加以区分,并在相应的颜色底纹上标注了所属的脑回名称图2㊀基于动态Hurst指数平均值的事后检验分析Figure2㊀Post⁃hocanalysisresultsonthemeanvalueofdynamicHurst图3㊀青年㊁中年㊁老年三组之间动态Hurst指数标准差有显著差异的脑区Figure3㊀Brainareadistributionmapwithsignificantdifferencesamongtheyoung,middle⁃agedandelderlygroupsusingthestandarddeviationofdynamicHurst(F=9 60,TFCE校正P=0 0094),其脑区分布如图4所示㊂此外,事后检验分析结果显示,在右侧楔前叶区域,存在显著差异的组别分别为中年组和老年组(t=-4 02,TFCE校正后P=0 0002),以及青年组和老年组(t=-3 49,TFCE校正后P=0 001)㊂3㊀讨论本研究基于年龄在19 80岁之间的458名健康受试者全脑动态Hurst指数的平均值㊁标准差和变异系数特征,分析不同年龄段人脑的动态复杂度水平和波动程度的群组差异,发现人脑老化过程中全脑各区域复杂度的动态变化模式并不一致,且在局部脑区上存在不同的组间统计显著差异模式㊂基于动态Hurst指数平均值的结果表明,人脑双侧颞上回㊁双侧岛回㊁右侧扣带回和双侧腹中侧枕叶皮质的复杂度随年龄增长而降低,双侧眶回和左侧楔前叶的复杂度随年龄的增长而呈现倒U形的变化㊂通过对动态Hurst指数标准差和变异系数的统计比较,发现老年组的右侧楔前叶的动态复杂度的变异程度显著大于青年组和中年组㊂动态Hurst指数的平均值可用于表征rs⁃fMRI㊃544㊃第5期㊀㊀㊀㊀㊀㊀倪黄晶,等:基于动态Hurst指数的人脑老化复杂度分析图4㊀青年㊁中年㊁老年三组之间动态Hurst指数变异系数有显著差异的脑区Figure4㊀Brainareadistributionmapwithsignificantdifferencesamongtheyoung,middle⁃agedandelderlygroupsusingthecoefficientofvariationofdynamicHurst信号的动态复杂度水平,其所得结果与Dong等[6]的研究结果基本一致,这说明动态Hurst指数可用于描述rs⁃fMRI信号的复杂度㊂随着年龄的增长,人脑各脑区的动态复杂度水平有增加或降低的趋势,这可能会导致个体随着年龄变化的认知水平和情绪控制等能力发生变化㊂在所探测出的具有显著群组差异的脑区中,颞上回的亚区数量最多㊂既往研究表明,颞上回是人脑听觉网络的重要区域,在语言的解释和产生[22]㊁从语音输入中提取有意义的语言特征等功能方面有重要作用[23]㊂既往研究[24-25]表明,老年人的语言理解能力基本能够保持,而听觉能力会有所下降,而大脑语言理解功能会增强进而补偿听觉的下降,这与本研究中观察到颞上回亚区的复杂度随年龄增加而出现线性下降或倒U形下降的现象相一致㊂此外,枕叶皮质主要负责视觉处理功能[26],本研究中发现腹中侧枕叶皮质的亚区呈线性下降的趋势,这与先前研究中报道的老年人群体的视觉功能会由于年龄增长而出现衰退的现象[27]相吻合㊂此外,岛回作为警醒网络的核心脑区,在运动㊁情感和认知功能之间的相互作用等方面起着重要作用[28]㊂青年㊁中年和老年3组被试在岛回亚区上随年龄增长而表现出线性下降的趋势,这可能与人脑老化过程中的认知功能衰退有关㊂变异系数是概率分布离散程度的归一化度量,是衡量数据中各观测值变异程度的统计量,其数值为标准差与平均值之比㊂本研究对动态Hurst指数的标准差和变异系数进行了组间统计比较,结果显示老年组的右侧楔前叶的动态Hurst指数的标准差和变异系数均显著大于青年组和中年组,而青年组和中年组之间无显著差异,据此可以推测在此脑区青年时期到中年时期没有明显的衰老,而中年时期到老年时期出现了显著的衰老,老年时期右侧楔前叶的动态波动离散程度显著变大㊂考虑到楔前叶与许多高水平的认知功能有关[29-31],并且该脑区所属的默认网络也被认为是脑老化过程中受破坏最严重的网络[32],因此该结果也提示了楔前叶区域在人脑老化研究中需要被重点关注㊂此外,本研究也存在如下局限性㊂首先,本研究使用的数据为横向静息态功能磁共振成像数据集,不同受试者之间的个体差异可能会影响最终的统计结果㊂考虑到对于同一被试在整个生命周期中的多次纵向数据采集的现实性不强,在未来的研究中采用Thompson等[33]研究者提出的被试多队列纵向设计也许是解决该问题的一个折中方案㊂其次,本研究只研究了大脑功能随年龄的变化情况,在未来的研究中可以整合脑结构信息,以对人脑的老化规律有一个更全面清晰的理解㊂4㊀结论本研究对458名19 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Mechanical Properties and Hemocompatibility of Nano-multilayered Ti/TiN Coated NiTiAHoy for Cardiac Occluder ApplicationAnlia ng Shao1,2渤,Yi Z ho u3‘41,Xiaoting Liu n,Yan Chen g3’矿,Tingfei X i1五3’4)★’JianxiaXu2’1)Wenzho u Me di cal College,Wenzhou 325035,Chi na2)Center of Medic al Devices,National Institu te f or Food an d Drug Control,Beijing100050,C hin a3)Biomedical e n g in e e r i n g r es e a r ch center,She nzhen inst ituti on of Pek ing U niversity,Shenzhen5 1 8057,China4)Center fo r Bio med ica l Materials and T i s s u e E ng ine eri ng,A ca dem y f or Advanced I nt e rd is c ip li n ar y St u d ie s,P e k i n gUniversity,Beijing 1 00871,C h i n a C orr esp on din g authors:chengyan@:pku.edu.cn;xitingfei@tom.com删films have been fabricated on NiTi alloy by multi—arc IAbstractl1-layer,5-laye r a nd9-la yer Tion p lat in g technique in our prese nt wo rk.T he sur fa ce m orph olog y an d phase structure of TiN/Ti filmwereterms of hemolysis rate,platelet adhesion,investigated by SEM,AFM an d XRD.H em oco mp ati bi lit y inpartial thromboplastin time(PTT),active partial thromboplastin time(APTT)and fibrinog en conce ntra tio n have been studied.The results show that th e su rf ace roughness for the c oa tin gs are hi gher th an that of th e NiTi substrate attributed to ion pl ati ng technique,and increase with the layer number.Na no hardn ess a n d elastic mod ulus valu es for th e TiffiN coating is mu ch hi gher th an t he NiTi alloy.The hemocompatibility t e st s indicate that the multi—layered Ti/TiN coating exhibits better hemolysis property,and have the comparable thrombus performance as th e substrate.Keywords:nano·multilayer;TiN/Ti;nanoindentation;hemocompatibility;NiTiTi/TiN纳米多层修饰的NiTi合金心脏封堵器的力学性能和血液相容性邵安良1Ⅲ’,周艺Ⅷ,刘晓婷”,成艳&咖,奚廷斐1·≈3’咖,许建霞21)温州医学院,浙江省温州市瓯海区茶山高教园区,3250352)医疗器械检测中心,中国食品药品检定研究院,北京市崇文区天坛西里2号,1000503)生物医学工程研究中心,北京大学深圳研究院,广东省深圳市南山区深圳市高新区南区高新南七道深港产学研基地大楼W320A,5180574)生物医用材料与组织工程中心,北京大学前言交叉学科研究院,北京市海淀区成府路205号,100871【摘要】在我们目前工作中,以NiTi为基体,通过多弧离子镀工艺制备出1层,5层,9层的TiN/Ti286薄膜。
·论 著·心房颤动患者口服华法林相关脑出血危险因素分析王 晶 王真奎 王 勋 施 倩 孙 伟 代大伟 张黎明【摘要】 目的 分析心房颤动(AF)患者口服华法林相关脑出血危险因素及预后情况,从而减低华法林相关脑出血(WAICH)的发生率与死亡率。
方法 本研究通过哈尔滨医科大学附属第一医院电子病历系统查找从2015年1月至2017年12 月在神经内科、外科住院AF患者WAICH患者20例和AF口服华法林无颅内出血患者30例为调查对象。
记录患者基本信息、既往史、危险因素、实验室检查、出院转归等方面进行整理。
同样方法搜集无出血组资料。
对上述资料进行SAS9.4软件统计学分析。
结果 经分析,出血组与无出血组在高血压病、缺血卒中史、出血史、治疗时间≤1年、血浆凝血酶原时间(PT)为30.36±22.53、活化部分凝血活酶时间(APTT)为43.88±17.75、国际标准化比值(INR)2.93±1.80、INR异变率、合并使用抗血小板药物、HAS-BLED评分为3.30±0.73有统计学差异(P<0.05),将上述单因素有意义的变量放入多因素Logistic模型中,采用逐步回归,结果表明PT,APTT,治疗时间长短是独立因素。
结论 高血压病、缺血卒中史、出血史、PT升高、APTT升高、INR增高、有INR异变率、治疗时间≤1年、合并应用抗血小板药物患者、HAS-BLED评分高是非瓣膜房颤(NVAF)患者口服华法林相关脑出血的危险因素;PT增高,APTT增高,治疗时间≤1年为NVAF口服华法林致WAICH的独立危险因素。
【关键词】 心房颤动; 华法林; 颅内出血; 出血危险因素中图分类号:R743.32 文献标识码:A 文章编号::1006-351X(2019)12-0768-05Analysis of oral warfarin -associated intracerebral hemorrhage in patients with nonvalvular atrial fibrillation. Wang Jing, Wang Zhenkui, Wang Xun,Shi Qian, Sun Wei, Dai Dawei,Zhang Liming. Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Heilongjiang 150000, China.Corresponding author: Zhang Liming, Email:zfxooo1@【Abstract】Objective To analyze the risk factors and prognosis of warfarin-related cerebral hemorrhagein patients with atrial fibrillation (AF), thereby reducing the incidence and mortality of warfarin-related cerebralhemorrhage (WAICH). Methods This study was conducted through the electronic medical record system ofthe First Affiliated Hospital of Harbin Medical University. From January 2015 to December 2017, 20 patients withWAICH in neurology and surgical hospitalized AF patients and 30 patients with AF oral warfarin without intracranialhemorrhage were investigated object. Record basic information, past history, risk factors, laboratory tests, and dischargeof patients. The same method was used to collect no bleeding group data. The above data were statistically analyzedby SAS 9.4 software. Results After analysis, the bleeding group and the non-bleeding group in the history ofhypertension, ischemic stroke, bleeding history, treatment time≤1 year, plasma prothrombin time (PT) was 30.36 ±22.53, activated partial thromboplastin time (APTT) 43.88±17.75, international normalized ratio (INR) 2.93±1.80,INR rate, combined use of antiplatelet drugs, HAS-BLED score of 3.30±0.73 were statistically significant (P<0.05).The variables were put into the multivariate Logistic model and stepwise regression was used. The results showed thatPT, APTT, the length of treatment was an independent factor. Conclusions Hypertension, history of ischemic stroke,history of hemorrhage, elevated PT, elevated APTT, increased INR, INR rate, treatment time ≤ 1 year, combinedantiplatelet drugs, high HAS-BLED scores are non-valvular atrial fibrillation(NVAF) patients risk factors for oralWAICH. PT increased, APTT increased, and treatment time ≤ 1 year was an independent risk factor for WAICH作者单位:150000 黑龙江,哈尔滨医科大学附属第一医院神经内科通信作者:张黎明, Email:zfxooo1@caused by oral administration of warfarin in NVAF.【Key words】 Atrial fibrillation; Warfarin ; Intracranial hemorrhage; Hemorrhage risk factors随着人口的老龄化日益严重,心房颤动(atrial fibrillation,AF)患者数量也随之增加,使应用口服抗凝血剂(oral anticoagulant therapy,OAT)人数增加。
doi:10.3969/j.issn.l000484X.2020.23.004细粒棘球蚴感染小鼠M-MDSC对Treg和Th17细胞增殖的调控①徐小丹王二强刘坪孟娟娟桂显伟武杰侯隽王仙吴向未陈雪玲(石河子大学医学院免疫学教研室,石河子832002)中图分类号R383.3文献标志码A文章编号1000-484X(2020)23-2832-05[摘要]目的:分析细粒棘球呦感染小鼠单核型髓源性抑制细胞(M-MDSC)分别对Th17和Treg细胞增殖的调控。
方法:C57BL/6小鼠随机分为对照组和感染组。
感染组小鼠肝脏注射活原头节5000只感染,对照组注射等体积PBS,于感染后的第30.90天无菌条件下取其脾细胞,流式细胞术检测MDSCs表达水平。
采用磁珠分选技术分离出感染30.90d小鼠脾脏中的M-MDSC,Ficoll分离液分离出naive小鼠脾脏中淋巴细胞,将M-MDSC与淋巴细胞以1:1比例共培养,4d后流式检测Th17和Treg细胞增殖情况。
结果:细粒棘球呦组小鼠(30、90d)脾脏中MDSC的表达率较对照组升高(P<0.01)。
与naive组相比,感染第30天时M-MDSC促进Th17增殖(P<0.05),但对Treg作用不明显,而感染第90天时,M-MDSC能够抑制Th17表达同时促进Treg表达。
结论:细粒棘球呦感染小鼠M-MDSC可能通过调节Th17和Treg的增殖参与宿主的免疫逃逸反应。
[关键词]细粒棘球呦;单核细胞型髓源性抑制细胞;Thl7;TregM-MDSC manipulate proliferation of Treg and Th17cells in mice infected Echinococcus granulosusXU Xiao-Dan,WANG Er-Qiang,LIU Ping,MENG Juan-Juan,GUI Xian-Wei,WU Jie,HOU Jun,WANG Xian,WU Xiang-Wei,CHEN Xue-Ling.Department of Immunology of Medical School,Shihezi University,Shihezi832002,China [Abstract]Objective:To investigate the proliferation of Th17and Treg cells manipulated by mononuclear myeloid derived suppressor cell(M-MDSC)in mice infected with Echinococcus granulosus.Methods:C57BL/6mice were divided into control group and infected group.Infected group was infected with E.granulosus through injected5000protoscoleces in live,while control group injected isopykinc PBS,spleen cells were collected under aseptic conditions at30d,90d after infection.Percentage of MDSCs were detected by FCM,and isolated magnetic bead separation technology was used to isolate M-MDSC.Splenic lymphocytes of naive mice were isolated by beled lymphocytes and sorted M-MDSCs were cocultivated at the ratio of1:1,after4days,evaluated the proliferation of Th17and Treg cells was by FCM.Results:Frequency of MDSCs in spleen was much higher in E.granulosus infected group than those in control group with statistic significances(P<0.01).Compared with naive group at post-infection30d,M-MDSC promoted proliferation of Th17(P<0.05),change of proliferation of Treg were not significant,while at90d post-infection M-MDSC promoted Treg proliferation and suppressed Th17proliferation(P<0.05).Conclusion:In the rats of E.granulosus infection,M-MDSC could regulate proliferation of Th17and Treg cells,indicated it may involve in host immune escape response.[Key words]Echinococcus granulosus;M-MDSC;Th17;Treg包虫病或称棘球蚴病(hydatid disease)是由细粒棘球呦绦虫的幼虫寄生于中间宿主引起的一种严重影响人畜健康的寄生虫疾病,主要分布于牧区,以细粒棘球呦引起的囊性包虫病为多见[1]o棘球呦感染早期无明显症状,但随着包囊体积增大,在感染①本文受国家自然科学基金(No.81760371.81760570.81602810)资助。
Statistical inversion for medical X-ray tomography with few radiographs I:General theoryS Siltanen1,V Kolehmainen2,S J¨a rvenp¨a¨a4,J P Kaipio2,PKoistinen4,M Lassas4,J Pirttil¨a5and E Somersalo31Instrumentarium Corp.Imaging Division,P.O.Box20,FIN-04301Tuusula,Finland2Department of Applied Physics,University of Kuopio,P.O.Box1627,FIN-70211Kuopio,Finland3Institute of Mathematics,P.O.Box1100,FIN-02015Helsinki University ofTechnology,Finland4Rolf Nevanlinna Institute,P.O.Box4,FIN-00014University of Helsinki,Finland5Invers Ltd.,T¨a htel¨a ntie54A,FIN-99600Sodankyl¨a,FinlandE-mail:Ville.Kolehmainen@uku.fiAbstract.In X-ray tomography,the structure of a three dimensional body isreconstructed from a collection of projection images of the body.Medical CT imagingdoes this using an extensive set of projections from all around the body.However,in many practical imaging situations only a small number of truncated projections isavailable from a limited angle of view.Three dimensional imaging using such datais complicated for two reasons:(i)Typically,sparse projection data does not containsufficient information to completely describe the3-D body,and(ii)Traditional CTreconstruction algorithms,such asfiltered backprojection,do not work well whenapplied to few irregularly spaced projections.Concerning(i),existing results about theinformation content of sparse projection data are reviewed and discussed.Concerning(ii),it is shown how Bayesian inversion methods can be used to incorporate a prioriinformation into the reconstruction method,leading to improved image quality overtraditional methods.Based on the discussion,a low-dose three-dimensional X-rayimaging modality is described.Submitted to:Phys.Med.Biol.1.IntroductionThree-dimensional X-ray imaging is based on acquiring several projection images of a body from different directions.If projection images are available from all around a two dimensional slice of the body,the classical work of Radon[72]shows that the inner structure of the slice can be determined.This result was reinvented by Cormack and Hounsfield and commercialized in the1970’s as Computerized Tomography(CT) imaging technology which is widely used in medicine today[11,12,82].We consider clinical imaging situations where three dimensional information is helpful but a complete CT-type projection data is not available.For instance,in mammography the breast is compressed against afixed detector and it is possible to move the X-ray source keeping the breast immobilized.However,the detector-beam angle should be relatively small and if the detector plane cannot be rotated,the projections can be obtained only from a relatively narrow aperture.The resulting reconstruction problem‡is an example of limited-angle tomography.Another type of situation occurs in extraoral dental imaging where some teeth are imaged with X-rays passing through other teeth and skull.The region of interest is surrounded by uninteresting tissue which is not attempted to be imaged.This situation is called local tomography.Apart from geometric restrictions,keeping the number of radiographs as small as possible to minimize radiation dose to the patient leads to sparse distribution of projection directions.We call the above type of data sparse projection data as opposed to traditional CT data.Three-dimensional medical X-ray imaging using sparse projection data can be viewed as an imaging modality of its own,made feasible by the digital revolution in X-ray imaging technology.It is suited for situations in which the sought-for diagnostic information can not be retrieved from any single projection image and a CT scan is not feasible due to low resolution,high radiation dose or cost of equipment.By its information content,this kind of imaging is obviously superior to studying a single radiograph.However,it differs significantly from CT imaging since sparse projection data does not contain enough information to completely describe a3-D body.Instead, only certain features of the body can be reliably reconstructed.What these features are depends both on data and available a priori information.It is well-known that traditional CT reconstruction algorithms do not produce satisfactory reconstructions when applied to sparse projection data,see Ranggayyan, Dhawan and Gordon[75],Natterer[64],Hanson[36],and references therein.In this paper we present and review results suggesting that statistical inversion methods can be succesfully used for reconstruction.The statistical inversion approach has the following benefits:•Any collection of projection data can be used for tomographic reconstruction.In particular,cone beam geometry and truncated projections are not more complicated to work with than parallel beam geometry and full projections.•Application-dependent a priori information on the target can be used in a natural and systematic way to recast the classically ill-posed problem in a well-posed stochastic form.With a well constructed prior model one can obtain improved image quality over traditional methods.Part I of this paper is a review paper.It brings together results from physics, mathematics and medical imaging in a way that is not usually considered in thefield ‡For historical reasons,we use occasionally the term reconstruction to mean any procedure to acquire information on the inner structures from X-ray measurements,although this term is quite inprecise,in particular from the point of view of statistical inference.of CT imaging.The rest of this part is organized as follows.In section2,we give a review of the mathematical results on the information content of sparse projection data.In section3,we discuss the theory of statistical inversion,the prior models and the computation of posterior statistics on rather general level.The likelihood model for the collection of projection data is also discussed.In section4,we describe a three dimensional X-ray imaging modality based on sparse projection data and give a review of statistical inversion approaches to X-ray tomography.In section5,we give conclusions. In part II of this paper we apply the general results to practical problems in dental radiology using experimental data.rmation content of sparse projection dataGeometrical arrangements of the X-ray source and digital sensor vary according to the diagnostic task and equipment.We illustrate here the types of tomographic data resulting from different imaging situations.For clarity we present two-dimensional examples,but similar situations can be considered in3-D as well.We separate two cases according to whether the whole object is fully visible in each projection or not,see Figure1.The case on the right in Figure1is called local tomography.Figure 1.Illustration of cone beam measurement geometry for transmissiontomography.Left:Global tomography.Right:Local tomography.The region ofinterest in denoted by ROI.In traditional CT imaging,projections are taken from all around the object.We sample the angular variable more sparsely in order to lower the radiation dose and due to geometrical limitations,see Figure2.In each of these four cases shown in Figure2, we might additionally have the local tomography situation.The types of data described above cover a large range of specific imaging tasks.The choice of data collection dictates what kind of features and details we can hope to reconstruct reliably from the data without a priori information on the body.filtered back-projection that do not use a priori information on the tissue.Careful analysis of collections of X-ray source locations in3-D space giving complete enough projection data for stable recovery has been given by Orlov[68],Tuy[92]and Finch [23].By the term stable it is meant here that the reconstruction from such data can be expected to represent the3-D object reliably.This situation falls outside the scope of this paper.The information content of sparse projection data depends on the type of sparsity. We discuss the effect of limited-angle and local tomography settings and the effect of reducing the number of radiographs.2.1.Limited-angle tomographyPerfect reconstruction from(an infinite set of)limited angle tomographic data is possible in principle,as discussed by Smith,Solmon and Wagner[85]and Natterer[64].However, the reconstruction problem is extremely ill-posed,or sensitive to measurement noise,as shown by Davison[14],Louis[58],Finch[23]and Tam and Perez-Mendez[88].Thus,a high quality reconstruction is not possible in practice without a priori information on the target.What features of the target can be reliably reconstructed using only the limited-angle data?A precise answer to this question is given by Quinto[71].One simple consequence of his results is that a sharp discontinuity,or jump along a curve,is reliably recoverable if and only if some X-ray in some of the projections is tangent to the curve.Otherwise the curve cannot be reconstructed by any algorithm from the projection data alone.We give examples of parts of boundary and cracks that are visible or indetectable in the reconstruction,see Figure3.In the recent work,Noo et al[66]give conditions for two dimensional cone beam projections that are needed to reconstruct a region of interest(ROI)within the object. Their result states that a ROI can be recovered accurately if i)the object is fully visible2.2.Local tomographyIn local tomography the region of interest is surrounded by tissue that is not reconstructed.This is often the consequence of small detector size forcing truncation of projections,or intentional minimization of radiation dose outside the region of interest. Local tomography was introduced by Smith and Keinert[83]and Vainberg,Kazak and Kurczaev[93].In this problem class the goal is to reconstruct the region of interest using only X-rays passing through it.It turns out that the actual attenuation function cannot be reconstructed but,instead,another function preserving sharp features can be recovered.This so-called lambda tomography was refined by Faridani,Finch,Ritman and Smith[20,21].In the above works on local tomography the3-D body is imaged from full view angle. The combination of local and limited-angle tomography is considered by Kuchment, Lancaster and Mogilevskaya[50]and Katsevich[45].The numerical examples in[50] are very illuminating.See also the book by Ramm and Katsevich[74],especially the images on pages254–257.The results are similar to limited-angle global tomography: Certain parts of singularity curves in the region of interest can be stably reconstructed. The parts are exactly those that have some measured X-rays as tangents.2.3.Few radiographsMost of the above results on reconstructable features from limited data assume that the data is available from a curve or other continuum of X-ray source positions.In practice data sets arefinite,and the number and directions of radiographs have an effect to the information content of the data set.As noted by Smith,Solmon and Wagner[85,Thm 4.2],afinite number of projections tells nothing at all about the volume since an almost arbitrary function can be added to the attenuation coefficient without changing the rmation content of projections has been studied further by Logan andShepp[57],Gr¨u nbaum[31],Hamaker and Solmon[32],Kazantsev[46],and Saksman, Nygr´e n and Markkanen[79].The analysis in the above references implies that problems caused by incomplete information content of afinite data set can be removed or greatly reduced by using a priori knowledge on the3-D body to exclude erroneous(oscillatory) features from the reconstruction.2.4.ConclusionThe discussion in this section suggests that high-quality tomographic reconstruction from sparse projection data is not possible without the use of a priori information. Note also that the above theoretical results concerning the reconstructable features in limited-angle and local tomography do not imply that any given practical tomographic algorithm is able to recover those features.In this paper we discuss how statistical inversion facilitates a systematic and natural way of incorporating a priori knowledge in tomographic reconstruction from sparse projection data,leading to improved reconstruction quality over traditional reconstruction methods.3.Statistical inversionThe following review papers provide more detailed analysis of several issues in statistical inversion approach than is given in this paper:Hanson[36],Tamminen[89],Mosegaard and Sambridge[62],Evans and Stark[19]and Kaipio et al[43].See also the work of Lehtinen[53,54,41].3.1.Basic definitionsThe success in solving ill-posed inverse problems depends heavily on how well one is able to make use of a priori information on the target.Particularly useful is information that is complementary to that extracted from the measurement.Such additional prior information is usually available:The practitioner has often a relatively good overall idea of what a typical target of the measurement should look like.The actual measurement is needed for additional specific information to distinguish from the general.From the computational point of view,this prior information may be rather qualitative in nature and work has to be done to translate it in a computationally useful quantitative form. The statistical inversion approach is a systematic andflexible way of incorporating in the inversion process extra infomation of the target of interest.The main idea in statistical inversion approach is to consider the inverse problem as a problem of Bayesian inference.All variables are redefined to be random variables.The randomness reflects our uncertainty of their actual values and the degree of uncertainty is coded in the probability distributions of these random variables.To keep the discussion tractable we consider linear measurement models with additive Gaussian errors:m=Ax+ ,(1)where the variables m∈R N,x∈R M and ∈R N are vector valued random variables§and A is the deterministic system matrix modelling the measurement.See section3.2 for an interpretation of tomographic X-ray measurements in the form of(1).When is Gaussian with zero mean and covariance matrixΓnoise,denoted ∼N(0,Γnoise),we havep noise( )∼exp −12 TΓ−1noise .(2) Let us mention that the statistical formulation does not depend on the Gaussian approximation.For an exposition of how to handle Poisson distributed observation models in inverse problems,see e.g.[96].Further,observe that if the noiseless model would be badly known,we could also model A by a random matrix.We assume here that the image vector x and the noise are independent.In terms of probability densities,this implies that their joint probability density is of the form p(x, )=p pr(x)p noise( ).(3) Here,p noise is the probability distribution of the noise that can be approximated,for example,by analyzing X-ray images from well-known phantom targets.The probability density p pr is called the prior density of the image.It is designed to contain all possible information that we have of the target prior to the measurement.It is crucial,in contrast to classical regularization methods,that the choice of the prior distribution should not be based on the data m.The proper design of the prior is an essential part of the statistical inversion procedure.The rule of thumb is that typical image vectors(say, of some existing library)should have high prior probability(density)while atypical or impossible ones should have low or negligible probability.Prior models are discussed in more detail in Section3.3.Having the joint probability of x and ,we may write the conditional probability of m,given x and formally asp(m|x, )=δ(m−Ax− ).(4)Here,δis the Dirac delta,i.e.,if x and were given,m would be completely determined. The joint probability distribution of x and m is then obtained asp(x,m)= R N p(m|x, )p(x, )d =p pr(x)p noise(m−Ax)(5) by straightforward substitution.Finally,the conditional probability distribution of x given the measurement m,or posterior density of x is given by the well-known Bayes’formulap(x|m)=p(x,m)p(m)=p pr(x)p(m|x)p(m),(6)§For notational convenience,we use the same lowercase notation for both,the random vector and its values.where p(m)is the marginal density of m and plays the role of a normalization constant. The density p(m|x)is called the likelihood density and is in this casep(m|x)=p noise(m−Ax).(7)It turns out that the density p(m)is in non-Gaussian posterior cases actually difficult to determine.Fortunately,it also turns out that the most important estimation methods that are based on the posterior distribution do not necessitate the determination of p(m).Thus the posterior density is usually considered in the non-normalized formp(x|m)∝p pr(x)p noise(m−Ax)(8)that is,the product of the prior and likelihood densities.In the framework of Bayesian inversion theory,the posterior distribution(6) represents the complete solution of the inverse problem,since it expresses our beliefs about the distribution of x based on all prior information and the measurement.Because the posterior distribution is a probability density in a large-dimensional space,we must have efficient tools to explore it.To produce an image of the target based on the posterior,several alternatives exist.The most common ones are the maximum a posteriori estimate(MAP)and conditional mean estimate(CM).They are defined by the formulasp(x MAP|m)=max p(x|m),(9) andx CM= R M xp(x|m)d x.(10) Observe that the MAP estimate is not necessarily unique,while the CM estimate is unique,provided that the integral converges.Finding the MAP estimate is an optimization problem whilefinding the CM estimate is a problem of integration.In addition to computing point estimates,the statistical inversion approach strongly suggests the computation of interval and uncertainty estimates as well as the marginal posterior densities of the variables themselves.An example of an interval estimate is the confidence interval,defined for a given0<τ<1as[a k,b k]⊂R where the endpoints a k and b k are determined byb k a k p k(x k)d x k=τ,p k(a k)=p k(b k),(11) where p k is the marginal posterior densityp k(x k)= R M−1p(x|m)d x1···d x k−1d x k+1···d x M.(12) Note that the confidence interval is not always well-defined.The most common uncertainty estimate is the posterior covarianceΓx|m= R M(x−x CM)(x−x CM)T p(x|m)d x(13)for In the with the aid of in Section3.6and a practical illustration of their significance is given in part II of this paper.3.2.Likelihood distribution for X-ray imagingIn this section,we discuss in more detail the likelihood model we use for X-ray imaging in this paper.In X-ray imaging,an almost pointlike X-ray source is placed on one side of an object under imaging.Radiation passes through the object and is detected on the other side, see ually the radiation is detected with X-rayfilm or a digital sensor that can be thought of as2-D arrays of almost pointlike detectors.The domain under imaging is modelled by a bounded subsetΩ⊂R3(orΩ⊂R2in 2D problems)together with a nonnegative attenuation coefficient x:Ω→[0,∞).The value x(s)gives the relative intensity loss of the X-ray travelling at s∈Ωwithin a small distance d s:d II=−x(s)d s.The X-ray has initial intensity I0when enteringΩand a smaller intensity I1when exitingΩ.We writeL x(s)d s=− 10I (s)d s I(s)=log I0−log I1,(14)where I0is known by calibration and I1from the corresponding point value in a projection image.Thus the measured data is the integral of x(s)along the line L.The discretization of the attenuation model involves dividing the domainΩinto a lattice of M disjoint3D-voxelsΩi(or2D-pixels),see Figure4,and measuring the length of the X-ray inside each voxel(or pixel).Assuming that the attenuation x is constant within each voxel(or pixel)Ωi,the attenuation map can be approximated in the formx≈Mi=1x iχi,(15)whereχi is the characteristic function of voxel(or pixel)Ωi in the lattice.Within the discretization(15),the attenuation map is identified by the coefficient vector x=(x1,x2,...,x M)T∈R ing the approximation(15),the line integrals through the domain can be approximated by weighted sum of voxel(or pixel)values,that is,L j x(s)d s≈M i=1x i|Ωi∩L j|,(16)where the subindex j denotes the measurement index.Arranging the set of projection data into a vector m=(m1,m2,...,m N)T∈R N,we get the equationm=Ax,(17) where matrix A implements the approximation(16)for the set of projection data.We note that the model(17)can be implemented for any data collection geometry.In the above model,we neglect scattering phenomena and effects of non-monochromatic radiation,such as beam hardening.See[80,1]for the former and[87] for the latter.The model(17)is assumed here to represent the noiseless observations.In practice, however,the measurement is corrupted by(at least)two noise types:•The detector is a photon counter,implying that the attenuated signal at each detector is a count n j∈N with expectationλj∈N,1≤j≤N.•The photon count of each detector is amplified electronically,causing electronic noise.The amplification noise of the counting process can reasonably be assumed to be multiplicative.Bearing in mind that the projection data(17)involves a logarithm of the count data,a reasonable model for the electronic noise is additive noise.A feasible model for the count vector n is to assume that each count n j is independent of the remaining ones and that n j has Poisson distribution with expectationλj.Therefore,we may writep(n|x)=Nj=1p Poisson(n j,λj)(18)=Nj=11n j!λn j j exp(−λj),λj=λ0I0exp −(Ax)j ,whereλ0is the probability that a photon is absorbed to the detector.However,in X-ray imaging a relatively large number of photons is usually detected at each detector pixel. In such case,the value of the likelihood density(18)can be well approximated with the value of a Gaussian approximation for the attenuation data of form(14)[7,78].A detailed discussion on this approximation is given in Appendix A.An approximation for the distribution of the electronic noise can be determined,for example,by careful analysis of the measurement electronics.However,this falls outside the scope of this paper.In this study we assume Gaussian distributions for the logarithms of both noise variables.Thus,the overall model for noise becomes the sum of two additive Gaussian random variables.The distribution of this new variable is convolution of two Gaussian distributions,which is again a Gaussian distribution.Therefore,we approximate the statistics of the overall measurement noise by ∼N(0,Γnoise),i.e.,the measurement noise is assumed to be normally distributed with zero mean and covariance matrixΓnoise that is assumed to be invertible.The likelihood distribution is thenp(m|x)=exp(−12(m−Ax)TΓ−1noise(m−Ax)).3.3.Prior modelsThe most crucial task in statistical inversion is the determination of a feasible prior. In particular,the translation of qualitative prior information into the language of probability densities is often a challenging problem.The general goal in designing priors is to assign a distribution p pr(x)with the following property.If E is a collection of expectable images and U is a collection of unexpectable images,we should havep pr(x) p pr(x )when x∈E,x ∈U.Thus,the prior probability distribution should be concentrated on expectable images and give them a clearly higher prior probability to occur than to those we do not expect to see.In many cases it turns out that certain expectable features can be formulated in the form of probability densities relatively easily while others may be very tricky if not impossible.A typical example of an easy task is when the image is expected to be smooth.In this case,one can use what is later called a smoothness prior.However,if we expect that in addition,the image contains infrequently occurring small anomalies that we would like to locate,the problem becomes more complicated.Indeed,using a smoothess prior we are very likely to fail detecting the anomaly since its occurrence probability with respect to that prior is extremely low.In the following we discuss briefly some of the methods for constructing prior models. The emphasis is onfinding a qualitative description of these prior models.In the following,it must be understood that when one talks about an image it is assumed that the pixel values(i.e.,values of the X-ray attenuation coefficient)are non-negative.This requirement means that the prior is proportional to the cut-offfunction,p pr(x)∝p+(x)=Mk=1θ(x k),(19)whereθis the Heaviside function.This cut-offfunction is not written out explicitly in the sequel.3.3.1.Generic Gaussian priors.The most widely used prior models are the Gaussian white noise and smoothness priors.Gaussian densities infinite dimensional spaces are generally of the formp pr(x)∝exp −12(x−x∗)TΓ−1pr(x−x∗) (20) where x∗is the mean vector andΓpr is the covariance matrix.The simplest one is undoubtedly the Gaussian white noise prior,p pr(x)∝exp −12σ2 x−x∗ 22 ,(21) i.e.,the covariance is assumed to be diagonal matrixΓpr=σ2I.This prior is by far the most commonly used implicit choice for prior model in the Tikhonov regularization approach for inverse problems(cf.formula(27)).The notion“white noise”is naturally related to the diagonal covariance structure which means that all image pixels are assumed to be uncorrelated.The standard deviation of each pixel around the assumed mean value x∗is given byσ.No structure of the image is assumed a priori.The smoothness priors in2D and3D are typically functions of associated directional derivatives.Perhaps the most commonly used smoothness prior for a2D pixel image in an equilateral P×P=M square mesh is given byp pr(x)∝exp −α k∈M ∈N k|x k−x |2 ,(22)whereαis a scaling parameter,M is the set of non-boundary pixels in the lattice (i.e.,M={Ωi|∂Ωi∩∂Ω=∅})and N k is the index set of four nearest pixels for the (non-boundary)pixel k(i.e.,N k={k−1,k+1,k−P,k+P}).The realization of the smoothness prior for higher orders and for non-regular meshes such as arbitrary triangular meshes may turn out to be more tedious.It also depends on the basis in which x is represented,see[42]for an example in which x is represented in piecewise linear rather than piecewise constant basis.A particular class of smoothness priors are anisotropic priors.These priors can be viewed as structural priors as they reflect structural information on the target. Therefore,we discuss them separately below.3.3.2.Impulse noise priors It is easy to generate prior densities based on pixelpresentation of the images.It is a less obvious task to describe what sort of qualitativeproperties they represent as an image.An important class of priors are the impulsenoise priors.In some applications,we expect to see a low-contrast image with fewoutstanding pixels as outliers.Such images appear e.g.in astronomy,where the sky isa nearly black object with bright stars.We mention here three of such priors.Theseare the L1–priorp pr(x)∝exp −αM k=1|x k| =exp(−α x 1),(23)the maximum entropy priorp pr(x)∝exp M k=1x k log x k x0 ,(24) and the Cauchy distribution prior,p pr(x)∝Mk=111+λx k.(25)In all of these priors,the pixels are uncorrelated.The performance of the maximum entropy prior and the L1–prior in recovering nearly black objects has been studied in the article[18].3.3.3.Reparametrized priors.In many cases the pixelwise parametrization of the image does not allow easily the coding of the prior information in form of a prior density. An illustrative example is that we know that the target contains a possibly unknown number of subregions in which the material parameters are constant.We may also know that the boundaries of these subregions are smooth.In this case it is then possible to parametrize the unknown variable for example with the aid of the material parameters inside all subdomains as well as the coefficients of the truncated Fourier series of the boundary curves.For an example in relation with optical tomography,see[47,48,49], and in relation to X-ray imaging,see[33,34,60,59].Also in the case of veryfine meshes it may turn out that the covariance matrix becomes almost singular.It is then advisable to consider lower dimensional(subspace) representations of the variable.In addition to making the overall estimation problem smaller dimensional,this may also increase the overall computational stability of the problem,since one often has to work also with the inverse of the covariance matrix. 3.3.4.Sample-based priors.In some cases one has access to a more or less representative ensemble of samples/images of the actual variable.One might for example have an ensemble of thoracical topographies of organs based on more extensive measurements(e.g.,anatomical atlases),or an ensemble of full angle reconstructions of teeth.In such cases,it is feasible to assume that the ensemble is distributed according to the prior.The problem is tofind a prior that would produce ensembles similar to the one at hand if samples were randomly drawn from the prior.This problem is recognized as a kernel estimation problem.As a general reference on kernel estimation methods we give[90].A particularly simple and computationally light special case is when the prior distribution underlying the ensemble can be approximated by a Gaussian distribution. One can then use the ensemble average as the prior mean and a low rank approximation for the inverse of the covariance matrix.In some cases it may also be possible to construct the ensemble artificially,see[94,95]for examples of this approach.。