發(fā)布時間：2018-01-14 00:24

  本文關(guān)鍵詞：IVIM不同測量方法和參數(shù)在直腸癌術(shù)前分期診斷效能的初步研究　出處：《山東大學(xué)》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 直腸癌 IVIM 穩(wěn)定性 耦合劑 分期

【摘要】：直腸癌發(fā)病率高,死亡率高,準(zhǔn)確診斷對于治療方法的選擇和預(yù)后非常重要。術(shù)前準(zhǔn)確評估直腸癌的TNM分期,對于手術(shù)方法的選擇非常有意義。T1-2期患者可以直接接受手術(shù)治療,而T3-4期或淋巴結(jié)陽性的腫瘤患者理論上需要推薦新輔助放化療,之后才可以接受手術(shù)治療。MRI對軟組織有較高的分辨能力,不僅對病灶顯示清楚,還具有功能性成像方法,可以對病變進行定量的診斷。IVIM(Intravoxel Incoherent Motion)為體素內(nèi)不相干運動,可以提供病變組織內(nèi)水分子的彌散情況和血管灌注情況,并以定量的形式表現(xiàn)出來,其參數(shù)包括D、D*和f值。惡性程度高的病變由于細胞增生旺盛,細胞核增大,導(dǎo)致水分子彌散受限,惡性程度低的病變以及良性病變彌散受限輕或不受限,以此可以對腫瘤的惡性程度、病理分期、淋巴結(jié)的侵犯情況進行無創(chuàng)性定量性的診斷。直腸自然狀態(tài)下腸腔閉鎖,直腸占位性病變,特別是潰瘍型病變與周圍正常腸壁組織甚至是腸腔內(nèi)容物互相靠近,使得病變邊界難以區(qū)分,這使得IVIM測量在勾勒病變范圍時不準(zhǔn)確,從而影響最后數(shù)值結(jié)果的穩(wěn)定性。此外,直腸腔內(nèi)的殘留氣體在IVIM序列掃描時會產(chǎn)生明顯的磁敏感偽影,對檢查和測量結(jié)果造成嚴重干擾;在IVIM ROI(Region Of Interest,感興趣區(qū))選擇時,不同的選擇方法也會對最終的結(jié)果產(chǎn)生影響,以上因素均會導(dǎo)致IVIM測量參數(shù)的變異性。腫瘤組織內(nèi)血管的生成情況影響腫瘤的生長速度以及對周圍或鄰近組織的浸潤、遠處轉(zhuǎn)移等生物學(xué)行為,從而影響腫瘤的預(yù)后。腫瘤血管生成的定量評估包括MVD和VEGF。腫瘤內(nèi)新生血管的測定,一方面可以對腫瘤術(shù)后復(fù)發(fā)和發(fā)生轉(zhuǎn)移的幾率進行評價,還可以為臨床醫(yī)生提供有助于制定治療方案的疾病信息,確定患者是否需要輔助放化療法。但MVD和VEGF均為術(shù)后病理學(xué)指標(biāo),無法在術(shù)前提供診療信息。尋找術(shù)前可以反應(yīng)MVD和VEGF的影像學(xué)參數(shù),對于提示預(yù)后和改進治療方案非常有意義。因此,研究目的包括:1比較直腸癌在自然狀態(tài)和使用耦合劑充盈后,結(jié)合不同的ROI選擇方法,包括邊緣勾勒法和小圓圈樣本法,觀察IVIM參數(shù)測量的穩(wěn)定性,以得到直腸癌IVIM最佳掃描及參數(shù)測量方法。2 探索IVIM參數(shù)在直腸癌T分期之間的差異性。3 探索淋巴結(jié)轉(zhuǎn)移和非轉(zhuǎn)移直腸癌病灶中IVIM參數(shù)的差異性,以期獲得一個定量提示淋巴結(jié)轉(zhuǎn)移的影像學(xué)指標(biāo)。4 探索D*和f值與MVD和VEGF的相關(guān)性,以期獲得一個術(shù)前無創(chuàng)性可反應(yīng)MVD和VEGF的影像學(xué)指標(biāo)。材料和方法本研究收集自2015年10月至2016年10月在本院接受直腸癌手術(shù)治療的患者共60例,術(shù)前均接受3.0T MR直腸序列掃描,男39例,女21例,年齡32-89歲,平均年齡57.3歲。使用GEHD750 3.0T磁共振掃描儀8通道體部專用相控陣線圈進行直腸磁共振檢查。掃描所用MRI常規(guī)序列包含矢狀位T2WI、軸位高清垂直病變T2WI、冠狀T2WI序列、軸位T1WI序列及軸位IVIM序列。IVIM序列,選用 11 個 b 值(0,20,50,100,150,200,400,600,800,1000,1500s/mm2)。在第二次IVIM序列掃描前,使用100ml一次性針管、灌腸管和超聲耦合劑勻速向直腸內(nèi)充盈耦合劑,根據(jù)直腸指檢、腸鏡或常規(guī)矢狀T2WI對病灶進行定位,以決定進管深度以及耦合劑注入量。選擇進管深度分別為:低位和中位直腸癌,以肛門為界,進管約5cm,高位直腸癌,以肛門為界,進管約10cm。耦合劑量分別約為 60-70、70-80、80-100ml。掃描完成后,將IVIM序列圖像傳輸至AW4.5 GE Medical Systems工作站,應(yīng)用Functool-MADC軟件進行分析,測量并記錄慢速表觀擴散系數(shù)D(slow apparent diffusion coefficient,Slow-ADC)值、快速表觀擴散系數(shù) D*(fast apparent diffusion coefficient,Fast-ADC)值和快速擴散所占比率f(fraction of fast-ADC,ffast)值,取兩組IVIM中b=1000相位測量,ROI選擇使用多層小圓圈樣本法和邊緣勾勒法兩種方法,每種方法測量五次,去除最大值和最小值,取三次平均作為最后數(shù)值。使用圓圈法時需保證每次圓圈大小相同,而邊緣法勾勒出高信號病變邊緣,以病變最大層面為中心。術(shù)后將標(biāo)本切片進行MVD和VEGF值測量。采用免疫組化法對切片進行處理。結(jié)果判定:(1)對于MVD:按照Weider的判斷標(biāo)準(zhǔn),微血管的定義為:任何可以被CD34抗體染棕黃色的內(nèi)皮細胞或細胞團,且可與鄰近組織分開。該微血管的分支,也可被認為是一個微血管計數(shù),前提是不與主微血管相連。(2)VEGF結(jié)果判讀:按照Volm的標(biāo)準(zhǔn),細胞內(nèi)胞漿顆�；蚣毎�膜,可以被VEGF單克隆抗體染成黃色者,即為VEGF陽性細胞。統(tǒng)計分析采用spss22和MedCalc軟件。符合正態(tài)分布的計量資料以均數(shù)±標(biāo)準(zhǔn)差(sx)表示。(1)采用組內(nèi)相關(guān)系數(shù)法(ICC)分析不同直腸狀態(tài)和ROI下IVIM參數(shù)的穩(wěn)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,確定最穩(wěn)定的直腸狀態(tài)和ROI。(2)使用根據(jù)方差齊性的結(jié)果采用t檢驗或t'檢驗進行直腸癌T1+T2和T3+T4分期之間、T2和T3期之間IVIM參數(shù)(D、D*和f)的差異性分析。(3)根據(jù)方差齊性的結(jié)果采用t檢驗或t'檢驗進行有轉(zhuǎn)移性淋巴結(jié)和無轉(zhuǎn)移性淋巴結(jié)的直腸癌病變之間IVIM參數(shù)(D、D*和f)的差異性分析。并對上述每個有意義參數(shù)的診斷效能進行評價,評價指標(biāo)選擇敏感性、特異性和ROC曲線及曲線下面積(AUC)。Youden index用來確定IVIM參數(shù)的最佳閾值。(4)利用spearman秩相關(guān)分析灌注相關(guān)參數(shù)D*和f值與MVD和VEGF的相關(guān)性。P0.05為統(tǒng)計學(xué)差異判定標(biāo)準(zhǔn)。研究結(jié)果1 IVIM各參數(shù)在不同直腸狀態(tài)和ROI選擇中穩(wěn)定性比較,結(jié)果如下:①對于D值,直腸充盈前+圓圈ROI、直腸充盈后+圓圈ROI、直腸充盈前+勾勒ROI、直腸充盈后+勾勒ROI的ICC分別為0.886、0.894、0.892、0.919;95%置信區(qū)間分別為0.778-0.946、0.794-0.950、0.789-0.949和0.843-0.962。②對于D*值,直腸充盈前+圓圈ROI、直腸充盈后+圓圈ROI、直腸充盈前+勾勒ROI、直腸充盈后+勾勒ROI的ICC分別為0.405、0.824、0.663和0.916;95%置信區(qū)間分別為0.156-0.719、0.657-0.917、0.345-0.841、0.836-0.960。③對于f值,直腸充盈前+圓圈ROI、直腸充盈后+圓圈ROI、直腸充盈前+勾勒ROI、直腸充盈后+勾勒ROI的ICC分別為0.682、0.684、0.808、0.835;95%置信區(qū)間分別為0.381-0.849、0.386-0.851、0.627-0.909、0.680-0.922�？梢�,直腸充盈后+勾勒法ROI其IVIM各參數(shù)的穩(wěn)定性最好,D、D*和f值的ICC分別為0.919、0.916、0.835。2在不同T分期(TT1+T2和T3+T4)之間,D、D*和f值的差異均具有統(tǒng)計學(xué)意義(p0.05),對于T1+T2期和T3+T4期直腸癌之間,T3+T4期D值、f值均數(shù)小于T1+T2期,而D*值大于T1+T2期。D、D*和f值之間的差異均具有統(tǒng)計學(xué)意義(p0.05)。單因素方差分析結(jié)果發(fā)現(xiàn),D值在T1+T2和T3+T4組中診斷效能最高,當(dāng)閾值為0.877×10-3時,AUC為0.711,特異性為83.33%,敏感性為55.56%。其次為f值,當(dāng)閾值為0.280時,AUC為0.704,特異性為72.22%,敏感性為64.29%。最后為D*值,當(dāng)閾值為8.02×10-3時,AUC為0.631,特異性為88.89%,敏感性為47.62%。多因素logistics分析結(jié)果發(fā)現(xiàn),D、D*和f值三個參數(shù)綜合診斷效能最高,閾值為0.665,AUC為0.806,特異性66.67%,敏感性83.33%。3在單純T2和T3期兩組之間D、D*的差異具有統(tǒng)計學(xué)意義(p0.05),T3期D值均數(shù)小于T2期,而D*值大于T2期,f值在兩組之間的差異不具有統(tǒng)計學(xué)意義(p0.05)。單因素方差分析,D值在T2和T3組中診斷效能最高,當(dāng)閾值為0.862×10-3時,AUC為0.779,特異性為86.67%,敏感性為63.64%。其次為D*值,當(dāng)閾值為8.02×10-3時,AUC為0.657,特異性為86.67%,敏感性為48.48%。擬合D和D*多因素logistics分析結(jié)果發(fā)現(xiàn),當(dāng)閾值為0.632時,AUC為0.897,特異性86.67%,敏感性81.82%。4對于有、無淋巴結(jié)轉(zhuǎn)移,D值在兩者之間的差異具有統(tǒng)計學(xué)意義(p0.05),無轉(zhuǎn)移組的D值高于有轉(zhuǎn)移組。D值閾值選擇為0.79×10-3時,AUC為0.629,敏感性為84.85%,特異性為48.15%。5 VEGF與D*之間spearman秩相關(guān)系數(shù)為0.50466,p值等于0.0073;VEGF與f之間spearman秩相關(guān)系數(shù)為-0.39358,p值等于0.0422;相關(guān)系數(shù)假設(shè)檢驗有統(tǒng)計學(xué)意義。MVD與D*之間spearman秩相關(guān)系數(shù)為-0.03115,p值等于0.8774;MVD與f之間spearman秩相關(guān)系數(shù)為0.11634,p值等于0.5634;相關(guān)系數(shù)假設(shè)檢驗無統(tǒng)計學(xué)意義。結(jié)論1 直腸充盈耦合劑后,結(jié)合病灶邊緣勾勒法選擇感興趣區(qū)域,可以獲得最穩(wěn)定的IVIM結(jié)果,在IVIM臨床推廣應(yīng)用上,非常有意義。2 IVIM可以輔助診斷直腸癌T分期情況,結(jié)合HR-T2WI圖像可提高T2與T3分期的準(zhǔn)確性。3 IVIM在一定程度上可以提示直腸癌患者淋巴結(jié)轉(zhuǎn)移的狀態(tài),這對治療方案的選擇和制定非常有意義。4 VEGF與D*值具有正相關(guān)性,與f值有負相關(guān)性,在一定程度上可以成為術(shù)前無創(chuàng)性預(yù)測VEGF的影像學(xué)指標(biāo)。意義經(jīng)腸道準(zhǔn)備和充盈耦合劑后獲得穩(wěn)定的IVIM參數(shù),可以應(yīng)用到直腸癌常規(guī)MRI檢查中,以對直腸癌進行全面綜合的評價,包括進行輔助T分期、提示淋巴結(jié)狀態(tài)、以及一定程度上預(yù)測VEGF來提示預(yù)后和改進治療方案。創(chuàng)新性1 探索了直腸充盈耦合劑后,以及選擇不同的ROI勾勒方法,對于IVIM穩(wěn)定性的影響,對IVIM標(biāo)準(zhǔn)掃描方案的制定具有重要意義;2 探索了利用IVIM定量參數(shù)對直腸癌T分期情況進行診斷,在一定程度上有助于臨床對于T2和T3期直腸癌的鑒別診斷;3 探索了利用病灶的IVIM參數(shù)來對淋巴結(jié)轉(zhuǎn)移情況進行評價,有利于治療方案的制定。4 探索利用無創(chuàng)性的影像學(xué)檢查方法,來預(yù)測術(shù)后病理學(xué)結(jié)果,對疾病的評價更加準(zhǔn)確和全面。不足1 總體樣本數(shù)量不足,不同T分期間的樣本不均,尤其是T1、T4期病例較少,可能會導(dǎo)致結(jié)果的偏倚。2 直腸充盈耦合劑會導(dǎo)致總體檢查時間的延長,同時,部分患者可能會有排斥心理。3 直腸充盈耦合劑導(dǎo)致直腸腔擴張,可能會導(dǎo)致在判斷環(huán)周切緣是否受累方面造成影響,并對病變距離肛緣位置的判斷造成影響。
[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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