本文選題：動物模型 + CT灌注��； 參考：《廣西醫(yī)科大學(xué)》2011年博士論文

【摘要】：目的在建立新西蘭兔VX2鼻咽癌模型的基礎(chǔ)上,對該模型進行放療后瘤灶區(qū)多層螺旋CT(MSCT)灌注成像與病理對照研究,探討借助該動物模型針對NPC放療后病灶性質(zhì)進行MSCT灌注診斷研究的病理基礎(chǔ)及其可行性,為尋求新的、適合臨床應(yīng)用于NPC放療后病灶性質(zhì)診斷的影像學(xué)手段奠定實驗研究基礎(chǔ)和相關(guān)理論基礎(chǔ)。 材料與方法在CT定位引導(dǎo)下將備置好的VX2腫瘤組織懸液注入新西蘭兔鼻咽頂后壁,建立兔VX2鼻咽癌模型；模型腫瘤放療結(jié)束1周后進行MSCT灌注成像,繼而進行病理解剖；將獲取的病灶區(qū)MSCT灌注參數(shù)等資料與相關(guān)病理資料進行對照研究。 結(jié)果22只新西蘭大白兔鼻咽部腫瘤移植成功并進入研究,接種4周后CT顯示其鼻咽部形成直徑為1.5cm-5cm之實性腫物,模型制作成功率為75.9%(22/29)。22只模型兔放療結(jié)束1周后病理檢查證實：鼻咽部腫瘤殘留組模型兔12只,無腫瘤殘留組模型兔10只；殘留組病灶MVD平均值高于非殘留組(P0.05)。CT灌注檢查顯示殘留組病灶BF、BV、PS值均數(shù)高于非殘留組(P0.05)、MTT值明顯低于非殘留組(P0.05),兩組病灶的BF、BV、PS值均與局部MVD值呈顯著的正相關(guān)性,而MTT值與MVD值均呈顯著的負相關(guān)性。 結(jié)論兔VX2動物模型腫瘤血供豐富,瘤株是低分化鱗狀細胞癌,與人類鼻咽癌的病理類型和生物學(xué)性質(zhì)有共性,故兔VX2鼻咽癌模型是人類鼻咽癌實驗研究較理想的動物模型。兔VX2鼻咽癌模型造模方法簡便易行且造模成功率高、研究中的可重復(fù)性好,動物大小及其鼻咽種植瘤等均適合于CT等影像學(xué)成像研究。兔VX2鼻咽癌模型放療后殘留組與非殘留組病灶局部的MSCT灌注參數(shù)以及MVD值均存在統(tǒng)計學(xué)差異,兩組病灶局部的MSCT灌注參數(shù)均與MVD值具有密切的相關(guān)性,故采用兔VX2鼻咽癌模型和MSCT灌注成像技術(shù)對鼻咽癌放療后病灶區(qū)的病變性質(zhì)進行鑒別診斷研究是具有可行性依據(jù)的,MSCT灌注成像極有可能成為新的、適合臨床應(yīng)用于NPC放療后病灶性質(zhì)診斷的影像學(xué)技術(shù)手段。 目的在前期動物模型研究結(jié)果的基礎(chǔ)上,利用CT灌注成像技術(shù)對人類鼻咽癌放療后病灶性質(zhì)進行前瞻性的臨床影像診斷和鑒別診斷研究,探討鼻咽癌放療后不同性質(zhì)病變的CT灌注特點及其鑒別診斷依據(jù),評價CT灌注成像技術(shù)在此臨床領(lǐng)域的應(yīng)用價值,為進一步提高鼻咽癌的總體療效尋求新的影像學(xué)技術(shù)手段。 方法對符合入組標(biāo)準(zhǔn)的174例T2-T3期鼻咽癌放療后患者進行多層螺旋CT (MSCT)灌注成像及病理檢查,將獲取的病灶區(qū)CT灌注參數(shù)等資料與相關(guān)病理資料進行對照研究,對病理證實的放療后局部殘留組(81例)和非殘留組(93例)病灶的CT灌注參數(shù)、時間密度曲線(TDC)形態(tài)及其MVD值進行組間差異性分析和灌注參數(shù)與MVD相關(guān)性分析。 結(jié)果人類鼻咽癌放療后局部殘留灶的TDC類型以“速升緩降型”和“速升速降型”為主,而非殘留灶的TDC類型以“緩升緩降型”和“平坦型”為主；局部殘留灶較非殘留灶具有更高的BF、BV、PS值及更低的MTT值,殘留灶與非殘留灶的上述CT灌注參數(shù)和TDC征象之間均存在統(tǒng)計學(xué)差異(P0.01)；人類鼻咽癌放療后局部殘留灶和非殘留灶的CT灌注值與病灶MVD的相關(guān)性研究結(jié)果類似于動物模型研究結(jié)果,即放療后病灶區(qū)的BF、BV、PS值亦均與MVD呈正相關(guān),MTT值亦與腫瘤MVD呈負相關(guān)。 結(jié)論①人類鼻咽癌與模型兔VX2鼻咽癌的CT灌注特點相類似,其放療后腫瘤殘留灶與非腫瘤殘留灶的CT灌注參數(shù)和TDC形態(tài)等均各具特點,且均存在統(tǒng)計學(xué)差異性,故采用CT灌注成像技術(shù)鑒別診斷人類鼻咽癌放療后病灶區(qū)的病變性質(zhì)是具備可行性依據(jù)的。②人類鼻咽癌放療后局部殘留灶TDC類型以“速升緩降型”和“速升速降型”為主,而非殘留灶的TDC類型以“緩升緩降型”和“平坦型”為主；局部殘留灶較非殘留灶具有更高的BF、BV、PS值及更低的MTT值；鑒于局部殘留灶與非殘留灶的上述CT灌注參數(shù)和TDC征象之間均存在統(tǒng)計學(xué)差異,故其可作為人類鼻咽癌放療后腫瘤殘留灶與非腫瘤殘留灶重要的CT灌注鑒別診斷依據(jù)。③人類鼻咽癌放療后局部殘留灶和非殘留灶的CT灌注值與病灶MVD的相關(guān)性研究結(jié)果類似于動物模型研究結(jié)果,即放療后病灶區(qū)的BF、BV、PS值亦均與MVD呈正相關(guān),MTT值亦與腫瘤MVD呈負相關(guān),故CT灌注成像技術(shù)有可能替代病理學(xué)活檢定性診斷和MVD分析,成為更適用于臨床應(yīng)用的、可較常規(guī)非功能影像學(xué)檢查更早期準(zhǔn)確地診斷鼻咽癌放療后局部病灶性質(zhì)和評估患者療效及預(yù)后的一種新的、有效和無創(chuàng)的功能影像學(xué)檢查手段。 目的研究鼻咽癌殘留病灶的CT灌注參數(shù)診斷臨界值,評價其對鼻咽癌放療后殘留病灶的診斷價值。 材料與方法本研究已獲得醫(yī)院和學(xué)校道德倫理審查委員會同意,所有病人檢查前均簽署知情同意書。研究對象為186例鼻咽癌放療后患者,其中男97例,女89例,年齡22-61歲,平均為43.2歲。186例病例按鼻咽部放療后瘤灶區(qū)活檢的病理結(jié)果分為兩組,其中殘留組87例,非殘留組99例。全部病例均采用GE 8層螺旋CT掃描機進行常規(guī)和灌注掃描；患者均采用仰臥位進行檢查；灌注分析之感興趣區(qū)均取在同一層面內(nèi)；常規(guī)平掃：掃描范圍上界為海綿竇上緣、下界為上頜骨齒槽突,層厚5 mm,重建間隔10mm,螺距0.625；灌注成像掃描：根據(jù)平掃圖像,選擇顯示腫塊(或原病灶區(qū))最大直徑的相鄰4層進行同層動態(tài)掃描；將造影劑首過前的圖像作為基準(zhǔn)圖像；掃描參數(shù)：80KV/80mAs,矩陣512×512,視野320mm×320mm,每層層厚設(shè)定為5mm,4層共掃描2cm厚度,注射速率4.5ml/s,延遲8s開始掃描,掃描速度4層/0.65s,共掃描55.65s。所有患者進行CT灌注掃描后,按病理結(jié)果分為兩組進行灌注參數(shù)分析研究,即殘留組(n=87)和非殘留組(n=99)。利用兩樣本t檢驗對兩組CT灌注值進行統(tǒng)計分析；在ROC曲線指導(dǎo)下,將有統(tǒng)計學(xué)有意義的CT灌注參數(shù)制成ROC曲線,確定診斷腫瘤殘留病灶的最佳診斷臨界值,計算該臨界值對腫瘤殘留病灶的診斷靈敏度、特異度以及ROC曲線下面積(AUC)。 結(jié)果鼻咽癌放療后殘留組和非殘留組之間的灌注參數(shù)BF、BV、PS值均數(shù)之間差異有統(tǒng)計學(xué)意義(P0.05),MTT值均數(shù)之間亦有統(tǒng)計學(xué)差異(P0.05)；BF、BV、PS參數(shù)診斷腫瘤殘留的最佳診斷臨界值分別為337.20(ml/100g/min)/10.18(100g/min)和17.34(ml/100g/min),其診斷腫瘤殘留的靈敏度分別為92.6%、96.3%和81.5%,特異度分別為76.2%、81%和61.9%,ROC曲線下面積分別為：0.891,0.938和0.780。雖然兩組MTT值均數(shù)之間有統(tǒng)計學(xué)差異,但兩組MTT值重疊多、無法獲得最佳診斷臨界值。 結(jié)論CT灌注成像參數(shù)可量化反映鼻咽癌放療后局部病灶區(qū)不同性質(zhì)組織或病變的血流動力學(xué)特征等功能信息；采用通過ROC曲線確定的鼻咽癌殘留病灶的CT灌注參數(shù)診斷臨界值作為量化診斷指標(biāo),能較準(zhǔn)確地對鼻咽癌放療后殘留病灶作出診斷和鑒別診斷。
[Abstract]:Objective to establish a New Zealand rabbit model of VX2 nasopharyngeal carcinoma (nasopharyngeal carcinoma), and to study the multislice spiral CT (MSCT) perfusion imaging and pathology of the tumor area after radiotherapy, and explore the pathological basis and feasibility of the MSCT perfusion diagnosis for the lesion properties of NPC after NPC radiotherapy, and to seek new and suitable clinical application. The imaging methods of lesion diagnosis after NPC radiotherapy laid the foundation for experimental research and related theoretical basis.
Materials and methods the VX2 tumor tissue suspension was injected into the posterior wall of the nasopharynx of New Zealand rabbits under the guidance of CT, and the rabbit VX2 nasopharyngeal carcinoma model was established. After 1 weeks of radiotherapy, the MSCT perfusion imaging was performed, and then the pathological anatomy was carried out. The data of the MSCT perfusion parameters in the lesion area were compared with the related pathological data. Study.
Results the nasopharyngeal tumor transplantation in 22 New Zealand rabbits was successful and entered the study. After 4 weeks of inoculation, CT showed that the nasopharynx was a solid tumor with a diameter of 1.5cm-5cm. The success rate of the model was 75.9% (22/29).22 model rabbit after 1 weeks of radiotherapy, and the pathological examination confirmed 12 rabbits in the nasopharyngeal tumor residual group, no tumor residual group model. The average value of MVD in the residual group was higher than that of the non residual group (P0.05).CT perfusion examination showed that the residual focus was BF, BV, PS value was higher than that of non residual group (P0.05), MTT value was significantly lower than that of non residual group (P0.05). The BF, BV, PS values were significantly positive correlation with the local values, and there was a significant negative correlation between the values and the values.
Conclusion the tumor of rabbit VX2 animal model is rich in blood supply. The tumor is a low differentiated squamous cell carcinoma. It is common to the pathological and biological characteristics of human nasopharyngeal carcinoma. Therefore, the rabbit VX2 nasopharyngeal carcinoma model is an ideal animal model for human nasopharyngeal carcinoma experimental study. The modeling method of rabbit VX2 nasopharyngeal carcinoma model is simple and easy to be used and the success rate of the model is high. Good reproducibility, animal size and nasopharyngeal implants were all suitable for CT imaging studies. There were statistical differences between the MSCT perfusion parameters and MVD values in the residual and non residual lesions of rabbit VX2 nasopharyngeal carcinoma model after radiotherapy, and the MSCT perfusion parameters in the two groups were closely related to the MVD value, so the rabbit VX2 was used in VX2. Nasopharyngeal carcinoma model and MSCT perfusion imaging are feasible for the differential diagnosis of the lesion properties of nasopharyngeal carcinoma after radiotherapy, and MSCT perfusion imaging is likely to be a new one, which is suitable for the clinical application of the imaging technique in the diagnosis of the nature of the lesion after NPC radiotherapy.
Objective based on the results of the previous animal model, CT perfusion imaging was used to make a prospective clinical imaging diagnosis and differential diagnosis of the nature of human nasopharyngeal carcinoma after radiotherapy, and to explore the characteristics of CT perfusion and the basis of differential diagnosis for different pathological changes of nasopharyngeal carcinoma after radiotherapy, and evaluate the CT perfusion imaging technique in this clinic. The application value of this field will provide new imaging techniques for further improving the overall efficacy of nasopharyngeal carcinoma.
Methods 174 cases of T2-T3 nasopharyngeal carcinoma after radiotherapy were treated with multi-slice spiral CT (MSCT) perfusion imaging and pathological examination. The data of CT perfusion parameters in the lesion area were compared with related pathological data, and the pathological confirmed local residual group (81 cases) and non residual group (93 cases) of CT perfusion parameters after radiotherapy were confirmed. The number, time density curve (TDC) shape and MVD value were used to analyze the difference among groups, and the correlation analysis between perfusion parameters and MVD.
Results the TDC types of the local residual foci in human nasopharyngeal carcinoma were mainly "speed rising and slowing down type" and "rapid descending type", while the TDC types of non residual foci were mainly "slow rise and slow down type" and "flat type", and the local residual foci had higher BF, BV, PS value and lower MTT value than non residual foci, and the residual and non residual foci above C. There were statistical differences between T perfusion parameters and TDC signs (P0.01). The correlation between CT perfusion of local residual and non residual foci after radiotherapy in human nasopharyngeal carcinoma was similar to that of animal model, that is, BF, BV, PS values were also positively correlated with MVD after radiotherapy, and MTT values were also negatively correlated with tumor MVD.
Conclusion (1) human nasopharyngeal carcinoma is similar to the CT perfusion characteristic of VX2 nasopharyngeal carcinoma in rabbit model. The CT perfusion parameters and TDC morphology of the residual tumor and non tumor residual foci after radiotherapy have different characteristics, and all have statistical differences. Therefore, CT perfusion imaging technique is used to identify the lesion properties of human nasopharyngeal carcinoma after radiotherapy. The local residual foci of TDC in human nasopharyngeal carcinoma were mainly "speed rise and slow down type" and "speed descending type", while the TDC types of non residual foci were mainly "slow rise and slow down type" and "flat type", and the local residual foci had higher BF, BV, PS value and lower MTT value than non residual foci; in view of local residue, the local residual foci were locally residual. There are statistical differences between the CT perfusion parameters and the TDC signs of the remaining and non residual foci, so it can be used as a basis for differential diagnosis of CT perfusion in the residual tumor and non tumor residual foci of human nasopharyngeal carcinoma after radiotherapy. (3) the correlation between the CT perfusion value of the local residual and non residual foci of human nasopharyngeal carcinoma after radiotherapy and the MVD of the lesion The results are similar to animal model studies, that is, BF, BV and PS values are also positively correlated with MVD, MTT values are also negatively correlated with tumor MVD, so CT perfusion imaging may be more suitable for clinical application in place of pathological biopsy and MVD analysis, which can be more early and accurate than conventional nonfunctional imaging examination. It is a new, effective and noninvasive functional imaging method for diagnosing the nature of local lesions and evaluating the curative effect and prognosis of nasopharyngeal carcinoma after radiotherapy.
Objective to study the diagnostic threshold of CT perfusion parameters for residual nasopharyngeal carcinoma (NPC) and evaluate its diagnostic value for residual lesions after radiotherapy for nasopharyngeal carcinoma.
Materials and methods have been approved by the hospital and school ethics review committee. All patients signed informed consent before the examination. The subjects were 186 cases of nasopharyngeal carcinoma after radiotherapy, including 97 males, 89 women, 22-61 years old, and an average of 43.2 years old.186 cases, divided into the pathological results of the tumor area biopsy after nasopharyngeal radiotherapy. In the two group, there were 87 cases in the residual group and 99 cases of non residual group. All cases were performed routine and perfusion scanning with GE 8 layer spiral CT scanner, and all the patients were examined in the supine position, and the region of interest in the perfusion analysis was taken at the same level; the routine scan was on the upper boundary of the cavernous sinus, the lower boundary was the maxillary alveolar process and the layer. Thickness 5 mm, reconstruction interval 10mm, spiral distance 0.625; perfusion imaging scan: according to plain scan image, select the adjacent 4 layers of the largest diameter of the mass (or the primary focus area) to perform the same layer dynamic scanning; the image before the contrast agent first is taken as the reference image; the scanning parameters: 80KV/80mAs, matrix 512 x 512, the field of vision 320mm x 320mm, each layer thickness set to 5 Mm, 4 layers were scanned with a total of 2cm thickness, injection rate 4.5ml/s, delayed 8s scan and scanning speed of 4 layers of /0.65s. After a total of 55.65s. patients were scanned by CT perfusion scan, the perfusion parameters were divided into two groups according to the pathological results, namely, the residual group (n=87) and the non residue group (n =99). The two groups of CT perfusion values were statistically divided by the two sample t test. Under the guidance of the ROC curve, a statistically meaningful CT perfusion parameter is made into a ROC curve to determine the best diagnostic critical value for the diagnosis of residual tumor, and to calculate the diagnostic sensitivity, specificity and area of the ROC curve (AUC) for the residual tumor.
Results the differences of perfusion parameters BF, BV and PS between the residual and non residual groups of nasopharyngeal carcinoma after radiotherapy were statistically significant (P0.05), and there was a statistical difference between the MTT values (P0.05). The optimal diagnostic critical values of BF, BV and PS parameters were 337.20 (ml/100g/min) /10.18 (100g/min) and 17.34, respectively, The sensitivity of the diagnosis of tumor residual was 92.6%, 96.3% and 81.5% respectively, the specificity was 76.2%, 81% and 61.9% respectively. The area under the ROC curve was respectively 0.891,0.938 and 0.780., although there were statistical differences between the two groups of MTT values, but the two groups of MTT overlapped more, and the best critical value of diagnosis could not be obtained.
Conclusion CT perfusion imaging parameters can be used to quantify the functional information of the hemodynamic characteristics of different tissues or lesions in the local lesion area of nasopharyngeal carcinoma after radiotherapy, and the critical value of CT perfusion parameters for the residual nasopharyngeal carcinoma identified by ROC curve as a quantitative diagnostic index can be more accurate for the residual focus of nasopharyngeal carcinoma after radiotherapy. Make a diagnosis and differential diagnosis.

【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R739.63

【引證文獻】

相關(guān)碩士學(xué)位論文 前1條

1 孟漢卿;磁共振成像對實驗兔鼻咽顱底結(jié)構(gòu)及其VX2癌侵犯的研究[D];廣西醫(yī)科大學(xué);2012年

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本文編號：1812381