IVIM不同测量方法和参数在直肠癌术前分期诊断效能的初步研究

发布时间：2018-01-14 00:24

  本文关键词：IVIM不同测量方法和参数在直肠癌术前分期诊断效能的初步研究　出处：《山东大学》2017年博士论文　论文类型：学位论文

  更多相关文章： 直肠癌 IVIM 稳定性 耦合剂 分期

【摘要】：直肠癌发病率高,死亡率高,准确诊断对于治疗方法的选择和预后非常重要。术前准确评估直肠癌的TNM分期,对于手术方法的选择非常有意义。T1-2期患者可以直接接受手术治疗,而T3-4期或淋巴结阳性的肿瘤患者理论上需要推荐新辅助放化疗,之后才可以接受手术治疗。MRI对软组织有较高的分辨能力,不仅对病灶显示清楚,还具有功能性成像方法,可以对病变进行定量的诊断。IVIM(Intravoxel Incoherent Motion)为体素内不相干运动,可以提供病变组织内水分子的弥散情况和血管灌注情况,并以定量的形式表现出来,其参数包括D、D*和f值。恶性程度高的病变由于细胞增生旺盛,细胞核增大,导致水分子弥散受限,恶性程度低的病变以及良性病变弥散受限轻或不受限,以此可以对肿瘤的恶性程度、病理分期、淋巴结的侵犯情况进行无创性定量性的诊断。直肠自然状态下肠腔闭锁,直肠占位性病变,特别是溃疡型病变与周围正常肠壁组织甚至是肠腔内容物互相靠近,使得病变边界难以区分,这使得IVIM测量在勾勒病变范围时不准确,从而影响最后数值结果的稳定性。此外,直肠腔内的残留气体在IVIM序列扫描时会产生明显的磁敏感伪影,对检查和测量结果造成严重干扰;在IVIM ROI(Region Of Interest,感兴趣区)选择时,不同的选择方法也会对最终的结果产生影响,以上因素均会导致IVIM测量参数的变异性。肿瘤组织内血管的生成情况影响肿瘤的生长速度以及对周围或邻近组织的浸润、远处转移等生物学行为,从而影响肿瘤的预后。肿瘤血管生成的定量评估包括MVD和VEGF。肿瘤内新生血管的测定,一方面可以对肿瘤术后复发和发生转移的几率进行评价,还可以为临床医生提供有助于制定治疗方案的疾病信息,确定患者是否需要辅助放化疗法。但MVD和VEGF均为术后病理学指标,无法在术前提供诊疗信息。寻找术前可以反应MVD和VEGF的影像学参数,对于提示预后和改进治疗方案非常有意义。因此,研究目的包括:1比较直肠癌在自然状态和使用耦合剂充盈后,结合不同的ROI选择方法,包括边缘勾勒法和小圆圈样本法,观察IVIM参数测量的稳定性,以得到直肠癌IVIM最佳扫描及参数测量方法。2 探索IVIM参数在直肠癌T分期之间的差异性。3 探索淋巴结转移和非转移直肠癌病灶中IVIM参数的差异性,以期获得一个定量提示淋巴结转移的影像学指标。4 探索D*和f值与MVD和VEGF的相关性,以期获得一个术前无创性可反应MVD和VEGF的影像学指标。材料和方法本研究收集自2015年10月至2016年10月在本院接受直肠癌手术治疗的患者共60例,术前均接受3.0T MR直肠序列扫描,男39例,女21例,年龄32-89岁,平均年龄57.3岁。使用GEHD750 3.0T磁共振扫描仪8通道体部专用相控阵线圈进行直肠磁共振检查。扫描所用MRI常规序列包含矢状位T2WI、轴位高清垂直病变T2WI、冠状T2WI序列、轴位T1WI序列及轴位IVIM序列。IVIM序列,选用 11 个 b 值(0,20,50,100,150,200,400,600,800,1000,1500s/mm2)。在第二次IVIM序列扫描前,使用100ml一次性针管、灌肠管和超声耦合剂匀速向直肠内充盈耦合剂,根据直肠指检、肠镜或常规矢状T2WI对病灶进行定位,以决定进管深度以及耦合剂注入量。选择进管深度分别为:低位和中位直肠癌,以肛门为界,进管约5cm,高位直肠癌,以肛门为界,进管约10cm。耦合剂量分别约为 60-70、70-80、80-100ml。扫描完成后,将IVIM序列图像传输至AW4.5 GE Medical Systems工作站,应用Functool-MADC软件进行分析,测量并记录慢速表观扩散系数D(slow apparent diffusion coefficient,Slow-ADC)值、快速表观扩散系数 D*(fast apparent diffusion coefficient,Fast-ADC)值和快速扩散所占比率f(fraction of fast-ADC,ffast)值,取两组IVIM中b=1000相位测量,ROI选择使用多层小圆圈样本法和边缘勾勒法两种方法,每种方法测量五次,去除最大值和最小值,取三次平均作为最后数值。使用圆圈法时需保证每次圆圈大小相同,而边缘法勾勒出高信号病变边缘,以病变最大层面为中心。术后将标本切片进行MVD和VEGF值测量。采用免疫组化法对切片进行处理。结果判定:(1)对于MVD:按照Weider的判断标准,微血管的定义为:任何可以被CD34抗体染棕黄色的内皮细胞或细胞团,且可与邻近组织分开。该微血管的分支,也可被认为是一个微血管计数,前提是不与主微血管相连。(2)VEGF结果判读:按照Volm的标准,细胞内胞浆颗粒或细胞膜,可以被VEGF单克隆抗体染成黄色者,即为VEGF阳性细胞。统计分析采用spss22和MedCalc软件。符合正态分布的计量资料以均数±标准差(sx)表示。(1)采用组内相关系数法(ICC)分析不同直肠状态和ROI下IVIM参数的稳定性。ICC0.4:一致性差;0.4ICC0.75:提示一致性一般到好;ICC0.75:提示有非常好的一致性,确定最稳定的直肠状态和ROI。(2)使用根据方差齐性的结果采用t检验或t'检验进行直肠癌T1+T2和T3+T4分期之间、T2和T3期之间IVIM参数(D、D*和f)的差异性分析。(3)根据方差齐性的结果采用t检验或t'检验进行有转移性淋巴结和无转移性淋巴结的直肠癌病变之间IVIM参数(D、D*和f)的差异性分析。并对上述每个有意义参数的诊断效能进行评价,评价指标选择敏感性、特异性和ROC曲线及曲线下面积(AUC)。Youden index用来确定IVIM参数的最佳阈值。(4)利用spearman秩相关分析灌注相关参数D*和f值与MVD和VEGF的相关性。P0.05为统计学差异判定标准。研究结果1 IVIM各参数在不同直肠状态和ROI选择中稳定性比较,结果如下:①对于D值,直肠充盈前+圆圈ROI、直肠充盈后+圆圈ROI、直肠充盈前+勾勒ROI、直肠充盈后+勾勒ROI的ICC分别为0.886、0.894、0.892、0.919;95%置信区间分别为0.778-0.946、0.794-0.950、0.789-0.949和0.843-0.962。②对于D*值,直肠充盈前+圆圈ROI、直肠充盈后+圆圈ROI、直肠充盈前+勾勒ROI、直肠充盈后+勾勒ROI的ICC分别为0.405、0.824、0.663和0.916;95%置信区间分别为0.156-0.719、0.657-0.917、0.345-0.841、0.836-0.960。③对于f值,直肠充盈前+圆圈ROI、直肠充盈后+圆圈ROI、直肠充盈前+勾勒ROI、直肠充盈后+勾勒ROI的ICC分别为0.682、0.684、0.808、0.835;95%置信区间分别为0.381-0.849、0.386-0.851、0.627-0.909、0.680-0.922。可见,直肠充盈后+勾勒法ROI其IVIM各参数的稳定性最好,D、D*和f值的ICC分别为0.919、0.916、0.835。2在不同T分期(TT1+T2和T3+T4)之间,D、D*和f值的差异均具有统计学意义(p0.05),对于T1+T2期和T3+T4期直肠癌之间,T3+T4期D值、f值均数小于T1+T2期,而D*值大于T1+T2期。D、D*和f值之间的差异均具有统计学意义(p0.05)。单因素方差分析结果发现,D值在T1+T2和T3+T4组中诊断效能最高,当阈值为0.877×10-3时,AUC为0.711,特异性为83.33%,敏感性为55.56%。其次为f值,当阈值为0.280时,AUC为0.704,特异性为72.22%,敏感性为64.29%。最后为D*值,当阈值为8.02×10-3时,AUC为0.631,特异性为88.89%,敏感性为47.62%。多因素logistics分析结果发现,D、D*和f值三个参数综合诊断效能最高,阈值为0.665,AUC为0.806,特异性66.67%,敏感性83.33%。3在单纯T2和T3期两组之间D、D*的差异具有统计学意义(p0.05),T3期D值均数小于T2期,而D*值大于T2期,f值在两组之间的差异不具有统计学意义(p0.05)。单因素方差分析,D值在T2和T3组中诊断效能最高,当阈值为0.862×10-3时,AUC为0.779,特异性为86.67%,敏感性为63.64%。其次为D*值,当阈值为8.02×10-3时,AUC为0.657,特异性为86.67%,敏感性为48.48%。拟合D和D*多因素logistics分析结果发现,当阈值为0.632时,AUC为0.897,特异性86.67%,敏感性81.82%。4对于有、无淋巴结转移,D值在两者之间的差异具有统计学意义(p0.05),无转移组的D值高于有转移组。D值阈值选择为0.79×10-3时,AUC为0.629,敏感性为84.85%,特异性为48.15%。5 VEGF与D*之间spearman秩相关系数为0.50466,p值等于0.0073;VEGF与f之间spearman秩相关系数为-0.39358,p值等于0.0422;相关系数假设检验有统计学意义。MVD与D*之间spearman秩相关系数为-0.03115,p值等于0.8774;MVD与f之间spearman秩相关系数为0.11634,p值等于0.5634;相关系数假设检验无统计学意义。结论1 直肠充盈耦合剂后,结合病灶边缘勾勒法选择感兴趣区域,可以获得最稳定的IVIM结果,在IVIM临床推广应用上,非常有意义。2 IVIM可以辅助诊断直肠癌T分期情况,结合HR-T2WI图像可提高T2与T3分期的准确性。3 IVIM在一定程度上可以提示直肠癌患者淋巴结转移的状态,这对治疗方案的选择和制定非常有意义。4 VEGF与D*值具有正相关性,与f值有负相关性,在一定程度上可以成为术前无创性预测VEGF的影像学指标。意义经肠道准备和充盈耦合剂后获得稳定的IVIM参数,可以应用到直肠癌常规MRI检查中,以对直肠癌进行全面综合的评价,包括进行辅助T分期、提示淋巴结状态、以及一定程度上预测VEGF来提示预后和改进治疗方案。创新性1 探索了直肠充盈耦合剂后,以及选择不同的ROI勾勒方法,对于IVIM稳定性的影响,对IVIM标准扫描方案的制定具有重要意义;2 探索了利用IVIM定量参数对直肠癌T分期情况进行诊断,在一定程度上有助于临床对于T2和T3期直肠癌的鉴别诊断;3 探索了利用病灶的IVIM参数来对淋巴结转移情况进行评价,有利于治疗方案的制定。4 探索利用无创性的影像学检查方法,来预测术后病理学结果,对疾病的评价更加准确和全面。不足1 总体样本数量不足,不同T分期间的样本不均,尤其是T1、T4期病例较少,可能会导致结果的偏倚。2 直肠充盈耦合剂会导致总体检查时间的延长,同时,部分患者可能会有排斥心理。3 直肠充盈耦合剂导致直肠腔扩张,可能会导致在判断环周切缘是否受累方面造成影响,并对病变距离肛缘位置的判断造成影响。
[Abstract]:Rectal cancer with high incidence, high mortality, accurate diagnosis and prognosis for treatment is very important. Accurate preoperative assessment of TNM staging in rectal cancer, for the choice of surgical methods have very importance in patients with stage.T1-2 can directly accept the surgical treatment, and T3-4 stage or lymph node positive patients with tumor theory need to recommend new adjuvant chemotherapy after, acceptable resolution of surgical treatment of.MRI are higher in soft tissue, not only focus on the clear display, also has the function of imaging method for diagnosis of.IVIM can be quantitatively to the lesion (Intravoxel Incoherent Motion) for intravoxel incoherent motion, can provide diffusion and perfusion of vascular lesions of the water molecule and, in a quantitative form, the parameters including D, D* and F value. The higher degree of malignant lesions due to cell proliferating cell nuclear, increased, resulting in water Sub restricted diffusion in low degree of malignant lesions and benign lesions are not limited or restricted diffusion of light, which can be the malignant degree of tumor, pathological staging, lymph node involvement for noninvasive diagnosis and quantitative. The natural state of intestinal atresia of rectum, rectal lesions, especially ulcerative lesions and the surrounding normal intestinal tissue and luminal contents close to each other, making the lesion boundary difficult to distinguish, which makes the IVIM measurement in the outline of lesion is not accurate, thus affecting the stability of final results. In addition, the residual gas of trananal produces significant magnetic sensitive artifacts in IVIM sequences, causing serious interference to check and measure the results; in the IVIM ROI (Region Of Interest, a region of interest) choice, different methods will also affect the final result, these factors will lead to IVIM measurement. The number of variability. Tumor angiogenesis effect of tumor growth rate and the infiltration of the surrounding or adjacent tissue, the biological behavior of distant metastasis, thus affecting the prognosis of tumor angiogenesis. Quantitative evaluation including MVD and VEGF. in tumor angiogenesis, one can of tumor recurrence and to evaluate the probability of metastasis, can also provide clinicians help to formulate treatment plan of disease information, determine whether patients need adjuvant chemoradiotherapy. But MVD and VEGF were diagnosed by postoperative pathology index, provide medical information before surgery. Before surgery can find no reaction of MVD and VEGF imaging parameters. To improve the treatment and prognosis of great significance. Therefore, this study includes: 1 Comparison of rectal cancer in the natural state and using the coupling agent after filling, with different ROI selection method, Including edge outline method and small circle sample method, observe the stability of the IVIM parameter measurement, measurement method to get optimal scanning parameters of.2 and IVIM rectal cancer to explore the IVIM parameters to explore the differences of lymph node metastasis and non metastasis of rectal cancer lesions in the IVIM parameter in the.3 difference between T staging, in order to obtain a quantitative tip lymph node metastasis imaging index.4 D* and explore the correlation between F value and MVD and VEGF, in order to obtain a preoperative noninvasive response MVD and VEGF imaging index. Materials and methods this study collected from October 2015 to October 2016 in our hospital for surgical treatment of colorectal cancer patients in 60 cases, preoperative 3.0T underwent rectal MR scanning, 39 cases were male, 21 were female, aged 32-89 years old, the average age of 57.3 years. The use of GEHD750 3.0T magnetic resonance scanner 8 channel special body phased array coil for magnetic resonance imaging of the rectum The MRI routine sequence scanning. Included sagittal T2WI, axial T2WI coronary lesions HD vertical, T2WI sequence, T1WI sequence and axial axial IVIM.IVIM sequences, using 11 b (0,20,5010015020040060080010001500s/mm2). In the second IVIM sequence scan before using the 100ml disposable syringes, enema tube and ultrasonic coupling agent uniform to the rectum filling couplant, according to digital rectal examination, locate the lesion of conventional colonoscopy or sagittal T2WI, to determine the inlet pipe depth and coupling agent dose. Selection of inlet pipe depths were: low and median rectal cancer, with the anus is bounded into the tube of about 5cm, with high rectal cancer, anus circle, inlet pipe coupling dose about 10cm. 60-70,70-80,80-100ml. respectively after the scan is complete, the IVIM GE Medical AW4.5 sequence image transmitted to the Systems workstation, using Functool-MADC software to analyze, measure and record the slow Rate of apparent diffusion coefficient D (slow apparent diffusion coefficient, Slow-ADC), fast apparent diffusion coefficient D* (fast apparent diffusion coefficient, Fast-ADC) and fast diffusion ratio of F (fraction of fast-ADC, ffast), b=1000 phase measurement of two sets of IVIM, ROI chose to use multilayer small circle sample method and edge outline two methods, each method of measurement five times, the removal of the maximum and minimum values, take three times the average as the final value. Use the circle method to ensure each circle of the same size, and the edge method outline hyperintense lesion edge, to the maximum level as the center. The postoperative specimens MVD and VEGF measurements. Immunohistochemical method was used to treat biopsy. Results: (1) for MVD: according to the standard of Weider, microvascular can be defined as any CD34 antibody staining of endothelial cells or brown The cell group, and can be separated from the surrounding tissue. The vascular branches can also be considered as a microvessel count, the premise is not with the main micro blood vessel connected. (2) VEGF: the interpretation of the results according to Volm standard, intracellular particles or cell membrane, can be dyed with VEGF monoclonal antibody yellow, which is VEGF positive cells. Statistical analysis using spss22 and MedCalc software. With normal distribution measurement data to mean + standard deviation (SX). (1) using intraclass correlation coefficient method (ICC) stability of.ICC0.4: consistency analysis of various parameters of IVIM and ROI under the condition of rectum; 0.4ICC0.75: that consistency generally good; ICC0.75: indicates a very good agreement, to determine the most stable state of the rectum and ROI. (2) used according to variance results using the t test or t'test T1+T2 and T3+T4 rectal cancer staging, IVIM parameters T2 and T3 phase (D, D* and F). Poor Specific analysis. (3) according to variance results by t test or t'test for metastatic lymph nodes and non metastatic lymph node lesions of colorectal cancer IVIM parameters (D, D* and F) analysis of differences. To evaluate the diagnostic efficacy and significance of each of these parameters, the selection of evaluation index the sensitivity, specificity and the area under the curve and the curve of ROC (AUC).Youden index to the optimal threshold to determine the parameters of IVIM. (4) using Spearman rank correlation analysis of perfusion related parameters of D* and f.P0.05 correlated with MVD and VEGF criteria for statistical difference. The results of the 1 IVIM parameters in different condition and stability of rectum ROI in comparison, results were as follows: 1. The D value of rectal fullness before ROI + circle, rectum filling circle + ROI, ROI + anterior rectal filling outline, rectum filling + ROI ICC outline were 0.886,0.894,0.892,0.919; 95% confidence interval Were 0.778-0.946,0.794-0.950,0.789-0.949 and 0.843-0.962. for the D* value of rectal fullness before ROI + circle, rectum filling + circle ROI, rectum filling before + outline ROI, rectum filling after ROI ICC outline + 0.405,0.824,0.663 and 0.916 respectively; 95% confidence intervals were 0.156-0.719,0.657-0.917,0.345-0.841,0.836-0.960. for F, ROI + circle before filling the rectum, rectum after filling the circle of ROI +, ROI + anterior rectal filling outline, rectum filling + ROI ICC outline were 0.682,0.684,0.808,0.835; 95% confidence intervals were 0.381-0.849,0.386-0.851,0.627-0.909,0.680-0.922. visible, the stability of rectum after filling method ROI the IVIM + outline the parameters of the best, D, D* and F values of ICC were 0.919,0.916,0.835.2 in different T stages (TT1+T2, D, and T3+T4) between D* and F values were statistically significant (P0.05), for T1+T2 and T3+T4 鐩磋偁鐧屼箣闂，

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