Value of CT Texture Analysis for Volumetric Changes of Abdominal Aortic Aneurysm after Endovascular Repair
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摘要:目的 探讨CT纹理分析对腹主动脉瘤腔内修补术(endovascular aneurysm repair, EVAR)后瘤体体积变化的评价意义。方法 回顾性收集2014年7月至2019年6月于北京协和医院放射科行腹盆部增强CT血管造影(computed tomography angiography, CTA)随访的EVAR术后患者的临床及影像学资料, 患者于术后第3、12个月分别接受两次腹盆部CTA检查, 以传统测量方法为分组依据, 根据动脉瘤体积变化情况将患者分为动脉瘤体积增大组和体积未增大组。采用分割软件, 手动勾勒所有动脉瘤术后第1次随访时轴位最大截面, 提取动脉瘤支架外血栓部分的纹理特征, 同时采用灰度共生矩阵(grey level co-occurrence matrix, GLCM)、灰度游程矩阵(grey level run length matrix, GLRLM)和灰度差分矩阵(grey level difference matrix, GLDM)3种方法, 分析其与动脉瘤体积增大的关系。结果 共70例符合纳入和排除标准的患者入选本研究, 其中29例(41.4%, 29/70)EVAR术后腹主动脉瘤体积增大, 41例(58.6%, 41/70)瘤体未增大。GLCM、GLRLM和GLDM 3种方法预测动脉瘤体积增大的曲线下面积分别为0.892、0.888和0.800, GLCM的预测效能最佳, 灵敏度和特异度分别为86.2%和85.4%, GLDM的曲线下面积最小, 灵敏度和特异度分别为86.2%和68.3%。结论 CT纹理分析能有效预测EVAR术后动脉瘤的体积变化。Abstract:Objective The aim of this study was to investigate the value of CT texture analysis for volumetric changes of abdominal aortic aneurysm (AAA) after endovascular aneurysm repair (EVAR).Methods Clinical and imaging data of patients with AAA undergoing CT angiography (CTA) at the 3rd and 12th months after EVAR in the Department of Radiology, Peking Union Medical College Hospital between July 2014 and June 2019 were retrospectively collected. Using the traditional measurement as the grouping basis, patients were divided into increased and no-increased groups according to the volume changes during the follow-up. Segmentation software was used to manually outline the maximum axial sections of all aneurysms and extract the texture features of the thrombus. The grey level co-occurrence matrix (GLCM), the grey level run length matrix(GLRLM), and the grey level difference matrix(GLDM) were calculated to analyzed their relationship with the enlargement of the aneurysm volume.Results A total of 70 patients meeting the inclusive and exclusive criteria were enrolled in this study, 29 cases (41.4%, 29/70) in the increased group and 41 (58.6%, 41/70) in the non-increased group. The areas under the ROC curve of GLCM, GLRLM, and GLDM for the diagnosis of increased volumes were 0.892, 0.888, and 0.800, respectively. The best prediction efficiency was shown in GLCM with the sensitivity and specificity of 86.2% and 85.4% respectively. GLDM had the worst pridiction efficiency with a sensitivity of 86.2% and a specificity of 68.3%.Conclusion CT texture analysis might predict the volumetric change of AAA after EVAR.
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Keywords:
- texture analysis /
- abdominal aortic aneurysm /
- volume /
- endovascular aneurysm repair
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原发性干燥综合征(primary Sjögren's syndrome, pSS)是一种慢性炎症性自身免疫性疾病, 可以造成多种器官和系统的损害, 病理上主要表现为受累组织炎症细胞浸润和次级生发中心的形成[1]。干燥综合征患者常有高γ球蛋白血症及多种自身抗体存在, 表明B细胞在干燥综合征患者为活化状态, 尤其是记忆性B细胞及浆细胞参与产生免疫球蛋白抗体的形成[2-3]。现已证实, 系统性红斑狼疮、类风湿关节炎、重症肌无力、系统性硬化症及干燥综合征等多种自身免疫性疾病常伴有血浆B细胞激活因子(Bcell activation factor, BAFF)水平的升高[4-5], 且其增高程度与自身抗体, 如抗双链DNA抗体(antidouble strand DNA antibody, 抗ds DNA抗体)、抗核抗体(antinuclear antibody, ANA)及类风湿因子(rheumatoid factor, RF)的效价高度相关[6], 尤其是干燥综合征患者血浆BAFF升高与高免疫球蛋白相关[7]。
对象和方法
对象
该研究与干燥综合征国际合作临床联盟(Sjögren's International Collaborative Clinical Alliance, SICCA)合作, 病例均来自SICCA确诊的干燥综合征患者, 诊断依据为2002干燥综合征国际分类(诊断)标准。pSS患者41例, 均为女性, 平均年龄(48. 7 ±9. 1)岁; 患者一级亲属7名, 均为女性, 平均年龄(50. 1±5. 0)岁; 健康自愿献血者27名, 为北京协和医院职工, 均为女性, 平均年龄(47. 0 ±3. 8)岁。
41例pSS患者中有口干症状34例, 有眼干症状25例; 有任意一侧腮腺肿大20例, 有任意一眼Schirmer试验结果≤5 mm25例, 双眼Schirmer试验结果均> 5 mm16例。血清IgG(19. 30 ± 5. 49) g /L, IgM(15. 58 ±0. 89) g /L, IgA(3. 14 ±1. 34) g /L, C3 (1. 18 ±0. 17) g /L, C4 (0. 27 ±0. 09) g /L。灶性指数(focus score) 2. 8 ±2, 眼科角结膜评分(oculars core) 8. 3 ±2. 6。
单克隆抗体及其他试剂
所用单克隆抗体及试剂包括FITC标记抗人CD19、PEcy5标记抗人CD27、PE标记抗人CD268 (BAFF-R), 以上抗体及试剂均购自美国eBioscience公司(San Diego, CA, USA)。人BAFFELI SA试剂盒来自Bender公司。所有实验均使用相同的IgG同型抗体作为对照。
方法
采集pSS患者、其一级亲属和正常对照者的空腹抗凝静脉血9 ml, 用淋巴细胞分离液对静脉血进行密度梯度离心, 制备外周血单个核细胞(peripheral blood mononuclear cells, PBMC)。
用含2%胎牛血清的磷酸盐缓冲液洗涤PBMC后, 进行荧光标记抗体的表面染色。在每1×106个/ml细胞中加入FITC-anti-CD19 (20 μl), PEcy5-anti-CD27 (20 μl), PE-anti-CD268 (BAFF-R) (10 μl), 4℃避光孵育30 min, 洗涤后用FACSAria型流式细胞仪(美国Becton —Dickinson公司)检测记忆性B细胞。
用Bender公司人BAFF ELISA试剂盒测定血浆BAFF水平。
统计学处理
所有数据均采用SPSS16. 0软件分析处理, 正态分布的计量资料用均数±标准差表示。经正态性和方差齐性检验, 正态分布数据, 方差齐的样品, 采用t检验进行平行组间比较, 采用配对t检验进行患者及其一级亲属的组间比较, 采用线性或曲线回归进行相关性分析。
结果
记忆性B细胞数目
pSS患者(n= 41)外周血CD 19 +CD 27 +B细胞为11. 10% ±5. 10%, 较正常对照者(n=27)的9. 24% ± 6. 99%显著增高, 两组比较差异有显著统计学意义(P=0. 0002)。
pSS患者(n=7)与其一级亲属(n=7)比较, CD19 +CD27+B细胞增高, 分别为16. 26 ±8. 30和8. 75 ±3. 82, 但两者比较差异均无显著统计学意义(P=0. 088)。
记忆性B细胞与临床资料的相关性
CD19 +CD27+B细胞和IgG、IgA、IgM、补体C3、补体C4、5-min未刺激唾液量、灶性指数(focus score)、眼科角结膜评分(ocular score)的相关性分析结果表明:CD19 +CD27 +B细胞与IgG、IgA、IgM、补体C3、补体C4均无相关关系(表 1); 与5-min未刺激唾液量呈正相关, r=0. 345, P= 0. 027 (表 1, 图 1); 与眼科角结膜评分呈负相关关系, r=-0. 321, P=0. 041 (表 1, 图 2)。
表 1 CD19 +CD27 +B细胞与临床资料的相关性依据口干、眼干症状、腮腺肿大及Schirmer试验结果对pSS患者进行分组, 分组后比较CD19 + CD27 +B细胞表达水平, 结果眼干组与无眼干组比较、口干组与无口干组比较、腮腺肿大组与无腮腺肿大组比较、双眼Schirmer试验任意一只眼≤5 mm组与双眼Schirmer试验均>5 mm组比较, 差异均无统计学意义(分别P=0. 883、P=0. 860、P= 0. 259、P=0. 392)。
BAFF水平比较
pSS患者(n=41)血浆BAFF为(1. 18±0. 72)ng /ml, 较正常对照者(n=27)的(0. 43 ±0. 19) ng /ml明显升高, 两组比较差异有极显著统计学意义(P=0. 0005)。而pSS患者(n=7)与其一级亲属(n=7)比较, BAFF水平明显升高, 分别为(1. 29 ±0. 46)和(0. 56 ±0. 11) ng /ml, 两者比较差异有统计学意义(P= 0. 015)。
BAFF与临床资料的相关性
pSS患者血浆BAFF与CD19 +CD27 +B细胞数目均无相关性(P=0. 624)。
pSS患者血浆BAFF与患者相关临床指标进行相关性分析结果表明:BAFF血浆浓度与IgG、IgA、IgM、补体C3、补体C4、5-min未刺激唾液量、灶性指数、眼科角结膜评分均无相关关系(表 2)。
表 2 BAF F血浆水平与临床资料的相关性根据口干、眼干、腮腺肿大及Schirmer试验分组对BAFF水平进行比较, 结果BAFF血浆浓度在有眼干组和无眼干组、有口干组和无口干组、有腮腺肿大组和无腮腺肿大组、双眼Schimer试验任意一只眼≤5mm组和双眼Schimer试验均>5 mm组间差异均无显著统计学意义(分别P=0. 154、P=0. 142、P=0. 789、P= 0. 691)。
讨论
干燥综合征被公认是B细胞活化的疾病, 表达在B细胞表面的CD27属肿瘤坏死因子受体家族, 可与Th细胞表面的CD70结合, 是B细胞活化的辅助刺激信号[8]。CD154 +CD70 +T细胞经由CD70 CD27途径在B细胞分化成浆细胞而起作用。干燥综合征患者B细胞活化, 分泌高γ球蛋白和自身抗体的浆细胞可能是发病的重要环节[9-10], 本实验检测CD19 +CD27+B细胞, 对pSS疾病发展过程中的记忆性B细胞予以探讨。结果表明pSS患者记忆性B细胞数目较正常人显著升高, 提示B细胞增殖参与了pSS发病; 此外, pSS患者与其一级亲属记忆性B细胞数目比较, 差异无显著统计学意义, 提示B细胞在pSS疾病发生之前可能已处于激活状态, 是疾病发生过程中的关键因素, 是导致疾病发生的原因而并非结果, B细胞数目测定对pSS的诊断和治疗可能具有提示作用。pSS患者外周血B细胞亚群与其临床、血清学指标均无相关关系, 提示记忆性B细胞可能与pSS发病相关, 而与疾病轻重或活动程度无关。近来有文章提出表达CD27+B细胞可根据是否表达IgD、IgM分群, 不同亚群对于该疾病的发病机制会起到不同的作用[11]。此外, 功能性B细胞可能在疾病发展过程中由外周血向腺体组织迁移, 因此检测局部受累组织中的记忆性B细胞数可能更为重要。因此检测外周如腺体或皮肤中的功能B细胞可能对诊断该疾病有重要意义[12]。
目前认为BAFF介导B细胞的活化、增殖、成熟、分化, 具有延长B细胞寿命, 阻止其凋亡, 并且促进生发中心形成的作用[13-14]。本研究发现pSS患者BAFF水平较正常人显著升高, 与理论预期符合, 且发现pSS患者与其一级亲属的BAFF水平比较差异无明显统计学意义。BAFF水平升高与CD27+B细胞数目增加的意义不同, 后者预示患者亲属体内的炎症细胞及其细胞因子可能处在预激活阶段, 参与pSS的发生; 而BAFF更可能参与pSS发生后的一系列反应而并非直接引起疾病的原因。鉴于本研究样本数太少(n=7), 此结论还需通过大样本实验进一步验证。BAFF与临床资料相关性研究表明, BAFF水平与pSS患者症状体征及血清学指标无明确相关关系, 提示BAFF尚不足以反映pSS的严重程度, 对pSS诊断治疗的意义尚不清楚, BAFF与pSS的关系尚有待于进一步研究。近期也有相关文章指出BAFF可能在利妥昔单抗治疗后的干燥综合征患者中对于B细胞分化有重要作用[15]。
利益冲突 无 -
表 1 腹主动脉瘤腔内修补术后动脉瘤体积的变化[M(P25, P75), cm3]
分组 术后3个月 术后12个月 Z值 P值 体积增大组(n=29) 114.6(88.7,226.2) 123.4(91.8,241.5) -4.703 <0.01 体积未增大组(n=41) 127.0(97.4,196.9) 114.2(78.7,183.5) -5.417 <0.01 表 2 3种灰度矩阵纹理分析技术对腹主动脉瘤腔内修补术后动脉瘤体积变化的诊断效能
纹理分析技术 曲线下面积 准确度 灵敏度 特异度 GLCM 0.892 0.859 0.862 0.854 GLDM 0.800 0.788 0.862 0.683 GLRLM 0.888 0.859 0.828 0.902 GLCM:灰度共生矩阵;GLRLM:灰度游程矩阵;GLDM:灰度差分矩阵 -
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