CT灌注成像对鼻咽癌放疗后瘤灶区病变性质判断的实验和临床研究

发布时间：2018-04-27 21:20

本文选题：动物模型 + CT灌注　；参考：《广西医科大学》2011年博士论文

【摘要】：目的在建立新西兰兔VX2鼻咽癌模型的基础上,对该模型进行放疗后瘤灶区多层螺旋CT(MSCT)灌注成像与病理对照研究,探讨借助该动物模型针对NPC放疗后病灶性质进行MSCT灌注诊断研究的病理基础及其可行性,为寻求新的、适合临床应用于NPC放疗后病灶性质诊断的影像学手段奠定实验研究基础和相关理论基础。材料与方法在CT定位引导下将备置好的VX2肿瘤组织悬液注入新西兰兔鼻咽顶后壁,建立兔VX2鼻咽癌模型；模型肿瘤放疗结束1周后进行MSCT灌注成像,继而进行病理解剖；将获取的病灶区MSCT灌注参数等资料与相关病理资料进行对照研究。结果22只新西兰大白兔鼻咽部肿瘤移植成功并进入研究,接种4周后CT显示其鼻咽部形成直径为1.5cm-5cm之实性肿物,模型制作成功率为75.9%(22/29)。22只模型兔放疗结束1周后病理检查证实：鼻咽部肿瘤残留组模型兔12只,无肿瘤残留组模型兔10只；残留组病灶MVD平均值高于非残留组(P0.05)。CT灌注检查显示残留组病灶BF、BV、PS值均数高于非残留组(P0.05)、MTT值明显低于非残留组(P0.05),两组病灶的BF、BV、PS值均与局部MVD值呈显著的正相关性,而MTT值与MVD值均呈显著的负相关性。结论兔VX2动物模型肿瘤血供丰富,瘤株是低分化鳞状细胞癌,与人类鼻咽癌的病理类型和生物学性质有共性,故兔VX2鼻咽癌模型是人类鼻咽癌实验研究较理想的动物模型。兔VX2鼻咽癌模型造模方法简便易行且造模成功率高、研究中的可重复性好,动物大小及其鼻咽种植瘤等均适合于CT等影像学成像研究。兔VX2鼻咽癌模型放疗后残留组与非残留组病灶局部的MSCT灌注参数以及MVD值均存在统计学差异,两组病灶局部的MSCT灌注参数均与MVD值具有密切的相关性,故采用兔VX2鼻咽癌模型和MSCT灌注成像技术对鼻咽癌放疗后病灶区的病变性质进行鉴别诊断研究是具有可行性依据的,MSCT灌注成像极有可能成为新的、适合临床应用于NPC放疗后病灶性质诊断的影像学技术手段。目的在前期动物模型研究结果的基础上,利用CT灌注成像技术对人类鼻咽癌放疗后病灶性质进行前瞻性的临床影像诊断和鉴别诊断研究,探讨鼻咽癌放疗后不同性质病变的CT灌注特点及其鉴别诊断依据,评价CT灌注成像技术在此临床领域的应用价值,为进一步提高鼻咽癌的总体疗效寻求新的影像学技术手段。方法对符合入组标准的174例T2-T3期鼻咽癌放疗后患者进行多层螺旋CT (MSCT)灌注成像及病理检查,将获取的病灶区CT灌注参数等资料与相关病理资料进行对照研究,对病理证实的放疗后局部残留组(81例)和非残留组(93例)病灶的CT灌注参数、时间密度曲线(TDC)形态及其MVD值进行组间差异性分析和灌注参数与MVD相关性分析。结果人类鼻咽癌放疗后局部残留灶的TDC类型以“速升缓降型”和“速升速降型”为主,而非残留灶的TDC类型以“缓升缓降型”和“平坦型”为主；局部残留灶较非残留灶具有更高的BF、BV、PS值及更低的MTT值,残留灶与非残留灶的上述CT灌注参数和TDC征象之间均存在统计学差异(P0.01)；人类鼻咽癌放疗后局部残留灶和非残留灶的CT灌注值与病灶MVD的相关性研究结果类似于动物模型研究结果,即放疗后病灶区的BF、BV、PS值亦均与MVD呈正相关,MTT值亦与肿瘤MVD呈负相关。结论①人类鼻咽癌与模型兔VX2鼻咽癌的CT灌注特点相类似,其放疗后肿瘤残留灶与非肿瘤残留灶的CT灌注参数和TDC形态等均各具特点,且均存在统计学差异性,故采用CT灌注成像技术鉴别诊断人类鼻咽癌放疗后病灶区的病变性质是具备可行性依据的。②人类鼻咽癌放疗后局部残留灶TDC类型以“速升缓降型”和“速升速降型”为主,而非残留灶的TDC类型以“缓升缓降型”和“平坦型”为主；局部残留灶较非残留灶具有更高的BF、BV、PS值及更低的MTT值；鉴于局部残留灶与非残留灶的上述CT灌注参数和TDC征象之间均存在统计学差异,故其可作为人类鼻咽癌放疗后肿瘤残留灶与非肿瘤残留灶重要的CT灌注鉴别诊断依据。③人类鼻咽癌放疗后局部残留灶和非残留灶的CT灌注值与病灶MVD的相关性研究结果类似于动物模型研究结果,即放疗后病灶区的BF、BV、PS值亦均与MVD呈正相关,MTT值亦与肿瘤MVD呈负相关,故CT灌注成像技术有可能替代病理学活检定性诊断和MVD分析,成为更适用于临床应用的、可较常规非功能影像学检查更早期准确地诊断鼻咽癌放疗后局部病灶性质和评估患者疗效及预后的一种新的、有效和无创的功能影像学检查手段。目的研究鼻咽癌残留病灶的CT灌注参数诊断临界值,评价其对鼻咽癌放疗后残留病灶的诊断价值。材料与方法本研究已获得医院和学校道德伦理审查委员会同意,所有病人检查前均签署知情同意书。研究对象为186例鼻咽癌放疗后患者,其中男97例,女89例,年龄22-61岁,平均为43.2岁。186例病例按鼻咽部放疗后瘤灶区活检的病理结果分为两组,其中残留组87例,非残留组99例。全部病例均采用GE 8层螺旋CT扫描机进行常规和灌注扫描；患者均采用仰卧位进行检查；灌注分析之感兴趣区均取在同一层面内；常规平扫：扫描范围上界为海绵窦上缘、下界为上颌骨齿槽突,层厚5 mm,重建间隔10mm,螺距0.625；灌注成像扫描：根据平扫图像,选择显示肿块(或原病灶区)最大直径的相邻4层进行同层动态扫描；将造影剂首过前的图像作为基准图像；扫描参数：80KV/80mAs,矩阵512×512,视野320mm×320mm,每层层厚设定为5mm,4层共扫描2cm厚度,注射速率4.5ml/s,延迟8s开始扫描,扫描速度4层/0.65s,共扫描55.65s。所有患者进行CT灌注扫描后,按病理结果分为两组进行灌注参数分析研究,即残留组(n=87)和非残留组(n=99)。利用两样本t检验对两组CT灌注值进行统计分析；在ROC曲线指导下,将有统计学有意义的CT灌注参数制成ROC曲线,确定诊断肿瘤残留病灶的最佳诊断临界值,计算该临界值对肿瘤残留病灶的诊断灵敏度、特异度以及ROC曲线下面积(AUC)。结果鼻咽癌放疗后残留组和非残留组之间的灌注参数BF、BV、PS值均数之间差异有统计学意义(P0.05),MTT值均数之间亦有统计学差异(P0.05)；BF、BV、PS参数诊断肿瘤残留的最佳诊断临界值分别为337.20(ml/100g/min)/10.18(100g/min)和17.34(ml/100g/min),其诊断肿瘤残留的灵敏度分别为92.6%、96.3%和81.5%,特异度分别为76.2%、81%和61.9%,ROC曲线下面积分别为：0.891,0.938和0.780。虽然两组MTT值均数之间有统计学差异,但两组MTT值重叠多、无法获得最佳诊断临界值。结论CT灌注成像参数可量化反映鼻咽癌放疗后局部病灶区不同性质组织或病变的血流动力学特征等功能信息；采用通过ROC曲线确定的鼻咽癌残留病灶的CT灌注参数诊断临界值作为量化诊断指标,能较准确地对鼻咽癌放疗后残留病灶作出诊断和鉴别诊断。
[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.

【学位授予单位】：广西医科大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R739.63

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