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Establishment Of Rabbit VX2 Nasopharyngealcarcinoma Invading Skull Base And Application In MR

Posted on:2012-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:G Q JinFull Text:PDF
GTID:1114330332494500Subject:Oncology
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Objective: To evaluate the feasibility of nasopharyngeal carcinoma invading the skull base by rabbit VX2 model, investigate the pathological foundation of MR diagnosing the nasopharyngeal carcinoma invading the skull base on rabbit VX2 model, and discriminate the physiological of the nasopharyngeal carcinoma and the adjacent structures by diffusion weighted imaging.Materials and Methods: This study was approved by the animal ethics committee before study participation according to institutional and native guidelines. 26 New Zealand white rabbit were underwent for establishing models of nasopharyngeal carcinoma invading the skull base, the gender have no contradistinction of all white rabbit, the weight of white rabbits ranged 2.5kg from 3.5 kg ( mean.3.0kg). One of 26 white rabbit was injected VX2 carcinoma cell for heredity in the lateral of thigh, and the carcinoma tissues were take out for carcinoma cell suspension when the white rabbit was anesthetized after 2 weeks. The others were received the CT scans, and were punctured, and injected the carcinoma cell suspension after white rabbits were anesthetized. The rabbits were underwent MR examinations after they were injected the carcinoma cell suspension after 2 weeks and 4 weeks. The growths of VX2 carcinoma in nasophargnx of the white rabbits were assessed by MR results. The successful models of VX2 carcinoma were calculated, and received the conventional MR and diffusion weighted image examination. The size and the intensity change of the skull base were recorded in the conventional MR. The apparent diffusion coefficient on the parenchyma, necrosis of VX2 nasopharyngeal carcinoma and the adjacent muscles were measured on diffusion weighted imaging. All successful rabbit models of VX2 nasopharyngeal carcinoma were executed after the conventional MR and DWI examinations. The characters of VX2 cacinoma cell, sizes of tumor, and information on invasion of the skull base were observed on the microscopy examinations. The sizes between conventional MR and pathology measurement were compared by matched t test for dependent samples. The apparent diffusion coefficients on the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles were analyzed by analysis of variance; the means of them were multiply compared by SNK-q test.Results: One New Zealand white rabbit was died in the course of puncture. In MR examination, the 72% (18/25) rate of rabbit VX2 nasopharyngeal carcinoma invading the skull base were made successfully. In MR examination, there had 18 cases of destruction on skull base in rabbit VX2 nasopharyngeal carcinoma, included the low intensity disappearances of cortical bone and the high intensity of bone marrow (n=12), the heterogeneous intensity disappearances of cortical bone and the high intensity of bone marrow (n=6), and there had two normal skull bases in rabbit VX2 nasopharyngeal carcinoma. The size of tumor was (3.5±0.8)cm in MR measurement. In microscopy examinations, there had 16 cases with destruction of trabecula bone and bone marrow, 2 cases with fibrosis and hyperplasy, and 2 normal skull bases. The size of tumors was (3.4±0.7)cm in pathology. There was no significant difference between MR and pathology measurement in VX2 carcinoma sizes(P>0.05). 100% sensitivity and 50% specificity of MR diagnosing the rabbit VX2 nasopharyngeal carcinoma invading the skull base were calculated according to pathological criteria. The ADC mean of the apparent diffusion coefficient on the parenchyma, necrosis of VX2 carcinoma, and the adjacent muscles were (1.10±0.28)×10-3mm2/s, (1.99±0.23)×10-3mm2/s , (1.67±0.17)×10 -3mm2/s, respectively. There had significant difference among the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles by analysis of variance(P<0.05), the their mean of multiply comparisons had statistical differences by SNK-q(P<0.05).Conclusions: The rabbit model of VX2 nasopharyngeal carcinoma invading skull base have some virtues ,such as high successful rate, low harm to animal, low fatality, convenient. The model of rabbit VX2 nasopharyngeal carcinoma invading skull base is near to the idealization of animal model criteria. The size, extent of invasion, and the physiological of the nasopharyngeal carcinoma and adjacent structure were evaluated by MR, for MR examination have high agreement with pathology. Objective: To evaluate the curative effect of nasopharyngeal carcinoma invading the skull base on rabbit VX2 model with radiotherapy by conventional MR and DWI examination, and the curative effect agreement of World health organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guideline were evaluated by MR examination.Materials and Methods: This study was approved by the animal ethics committee before study participation according to institutional and native guidelines. 32 New Zealand white rabbit were underwent for establishing models of nasopharyngeal carcinoma invading the skull base, the gender have no contradistinction of all white rabbit, the weight of white rabbits ranged 2.0kg to 3.5 kg ( mean,2.8kg). All white rabbits were received the radiotherapy with dose of per 5Gy in every other day, the whole time of radiotherapy was 4 week. Conventional MR and diffusion weighted imaging in white rabbit VX2 nasopharyngeal carcinoma invading the skull base were practiced pre-, post-radiotherapy. Sizes and areas of the rabbit VX2 tumor were recorded in the conventional MR before and after radiotherapy. The apparent diffusion coefficient on the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles were measured on diffusion weighted imaging before and after radiotherapy. The effective rates of CR, PR, SD, and PD of MR evaluation were calculated according the WHO and RECIST criteria.The sizes and area of rabbit VX2 carcinoma before and after radiotherapy on conventional MR were compared by matched t test for dependent samples. The apparent diffusion coefficients on the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles were analyzed by analysis of variance; the means of them were multiply compared by SNK-q test. The effective rates were compared by R×C X2 test. The curative effect agreement of WHO and RECIST criteria was assessed Kappa values.Results: 26 New Zealand white rabbits VX2 nasopharyngeal carcinoma were received conventional MR and DWI examination before and after radiotherapy. The mean diameter(2.79±0.71cm) of rabbit VX2 nasopharyngeal carcinoma invading skull base before radiotherapy was significant larger than that(1.01±0.92cm) after radiotherapy(P<0.05). The mean area(6.97±3.68cm2) of rabbit VX2 nasopharyngeal carcinoma invading skull base before radiotherapy was significant larger than that(1.54±0.94cm2) after radiotherapy(P<0.05). The ADC mean of the apparent diffusion coefficient on the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles before and after radiotherapy were (1.10±0.18)×10-3mm2/s versus(1.57±0.35)×10-3mm2/s(P<0.05), (2.1±0.36)×10-3mm2/s versus(2.3±0.51)×10-3mm2/s(P>0.05), (1.79±0.22)×10-3mm2/s versus(1.67±0.17)×10-3mm2/s(P>0.05), respectively. There had significant difference among the parenchyma, necrosis of VX2 carcinoma and the adjacent muscles before and after radiotherapy by analysis of variance(P<0.05), only mean of the parenchyma of VX2 carcinoma between pre and post therapy had statistical differences by SNK-q(P<0.05). The rates of CR, PR, SD, and PD according WHO and RECIST criteria were CR 26.9 % (7/26) vs CR 26.9% ( 7/26 ), PR 53.9% (14 /26)vs61.5 %(16 /26) , SD% 15.4 ( 4/26 )vs7.7 % ( 2/26 ),PD 3.8%( 1/26)vs 3.8%( 1/26), respectively. The effective rates of WHO(80.8%) was lower that of RECIST(88.4%), but there was no differenceo on curative effect between WHO and RECIST criteria(P>0.05). The Kappa values in agreement between WHO and RECIST criteria was 0.7.Conclusions: conventional MR do well in evaluating the change of rabbit VX2 nasopharyngeal carcinoma invading skull base with radiotherapy; the curative effect outcome between WHO and RECIST criteria has a good agreement by conventional MR examination. The DWI can reflect the pathological alteration on rabbit VX2 nasopharyngeal carcinoma invading the skull base, may be a new instrument for evaluation of nasopharyngeal carcinoma effective rate. Objective: To research the feasibility values of curative effect on New Zealand white rabbit VX2 nasopharyngeal carcinoma invading the skull base by CT perfusion examination, and explore the correlation between CT perfusion parameters and micro-vessel density on rabbit VX2 nasopharyngeal carcinoma invading the skull base with pre-,post-radiotherapy. Materials and Methods: This study was approved by the animal ethics committee before study participation according to institutional and native guidelines. 26 New Zealand white rabbit had established models of VX2 nasopharyngeal carcinoma invading the skull base, the gender have no contradistinction of all white rabbit, the weight of white rabbits ranged 2.0kg to 3.5kg ( mean, 2.8kg). All white rabbits were received the radiotherapy with dose of per 5Gy in every other day, the whole time of radiotherapy was 4 weeks. CT perfusion scans and pathological examination in white rabbit VX2 nasopharyngeal carcinoma invading the skull base were practiced pre-, post-radiotherapy. The CT perfusion parameters, such BF, BV, PS, and MTT were generated. Numbers of micro-vessel density were calculated in all white rabbits. The effective rates of all CT perfusion parameters in all white rabbits were evaluated according to 30% change of CT perfusion parameters from pre- to post-radiotherapy. The mean of CT perfusion parameters of all white rabbit with pre-, post-radiotherapy were compared by two sample t test for independent samples. The effective rates were compared by R×C X2 test. Correlation between the CT perfusion parameters and micro-vessel density were compared linear correlation.Results: The BF values of all New Zealand white rabbits VX2 nasopharyngeal carcinoma invading the skull base ranged 45.3 to 845.1(ml/100g/min )(mean 493.5±117.7) before radiotherapy, ranged 10.8 to 483.6(ml/100g/min)(mean 123.5±53.8) after radiotherapy; The BV values ranged 11.2 to 62.5 (100g/min)(mean 36.8±17.6) before radiotherapy, ranged 4.2 to 22.3( 100g/min) (mean 9.4±2.9) after radiotherapy; The PS values ranged 16.8 to 93.6(ml/100g/min)(mean 55.4±24.3) before radiotherapy, ranged 3.5 to 29.3(ml/100g/min)(mean 14.9±4.7) after radiotherapy; The MTT values ranged 1.3 to 7.5sec(mean 3.4±1.1) before radiotherapy, ranged 2.2 to 13.2(sec) (mean4.6±2.0) after radiotherapy; The effective rates of all CT perfusion parameters (BF, BV, PS, and MTT) evluation were 88.5%, 80.8%, 92.3%, and 84.6%, respectively. There had significant differences on CT perfusion parameter BF, BV, PS, and MTT of rabbits between pre- and post-radiotherapy(P<0.05). There was no statistical difference among all effective rates of CT perfusion parameters BF, BV, PS, and MTT evaluation(P>0.05). Coefficient of product moment correlation between BF, BV, PS, and MTT and micro-vessel density before and after radiotherapy were 0.87,0.90, 0.83 , -0.78, and 0.85 , 0.82 , 0.81 , -0.79, respectively.Conclusion: There had positive correlation between BF, BV, and PS and micro-vessel density, and negative correlation between MTT and micro-vessel density. CT perfusion may mirror the structure change of rabbit VX2 nasopharyngeal carcinoma invading the skull base with radiotherapy, will be a new measurement for evaluation of nasopharyngeal carcinoma effective rate.
Keywords/Search Tags:animal model, VX2, nasopharyngeal carcinoma, magnetic resonance, diffusion weighted imaging, VX2 animal model, solid tumor, nasopharyngeal carcinoma effective rate, CT perfusion, micro-vessel density
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