【作者】 兰为顺；

【导师】 胡道予；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2013， 博士

【摘要】 第一部分：兔软组织VX2肿瘤模型的建立及MR介导的无水乙醇瘤内注射消融治疗目的：建立兔软组织VX2肿瘤模型,并在MR介导下行无水乙醇瘤内注射消融治疗,为后期功能性MRI评价疗效打下基础。方法：15只健康新西兰大白兔,雌雄不限,体重2.5-3kg,在其右侧后大腿内侧肌肉内注入准备好的VX2肿瘤细胞悬浮液各约0.2ml,在种植肿瘤后的第14天行常规磁共振扫描,观察肿瘤种植的成功率及肿瘤的形态、大小、信号特点等。扫描后的第二天再在MR介导下行无水乙醇瘤内注射消融治疗。利用T2WI作为导引及监测手段,将带侧孔的MR兼容穿刺针刺入病灶中心,按肿瘤直径1ml/cm的量向瘤内缓慢注射无水乙醇,对肿瘤进行消融治疗。T2WI监测无水乙醇在病灶内的弥散和分布。术后10天,处死所有实验兔,剥离肿瘤组织进行病理检查。结果：15只兔右侧后大腿内侧种植肿瘤均成功,成功率为100%。常规磁共振扫描右侧后大腿内侧的肿块呈类圆形,直径约3-4cm,T1WI月中瘤呈等信号或稍低信号,肿瘤中心可见更低信号的坏死区。T2WI肿瘤呈高信号,中心坏死区为更高信号。肿瘤周边见高信号的水肿带；15只兔均成功进行了MR介导下的无水乙醇瘤内注射消融术,术中注射无水乙醇平均3.5ml。T2WI能清晰的监测无水乙醇在瘤内的弥散和分布。病理检查示：术前肿块周边肿瘤细胞密集,排列呈巢状,肿瘤细胞核大而深染,部分可见核分裂像。肿块中心可见少许黄白色豆腐渣样坏死组织。术后10天肿块周边肿瘤组织大部分凝固性坏死崩解,肿瘤坏死率约85-90%,仅见少数残存的肿瘤细胞,肿块中心坏死范围较术前明显增大。结论：兔软组织VX2肿瘤模型的建立操作简单,成瘤率高,是适合用作评价肿瘤疗效的动物模型；MR介导下行无水乙醇瘤内注射具有良好的肿瘤消融疗效,磁共振T2WI可以清晰的监测无水乙醇在瘤内的弥散和分布,是一种好的导引和监测肿瘤消融治疗的影像学方法。第二部分：磁共振弥散加权成像评价无水乙醇消融治疗兔软组织VX2肿瘤疗效的实验研究目的：利用磁共振弥散加权成像(DWI)来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效。材料和方法：15只新西兰大白兔,雌雄不限,体重2.5-3kg,在其右侧大腿内侧注射VX2肿瘤组织悬浮液各约0.2ml,制备成荷瘤兔,于肿瘤组织接种后第14天行常规磁共振扫描及多个b值(300、500、700、900s/mm2)的DWI扫描,扫描后第2天在磁共振导引及监视下行无水乙醇瘤内注射消融治疗。消融治疗后分别于第1、7、10天再行常规磁共振扫描及多个b值的DWI扫描,扫描参数与术前一致。观察术前与术后肿瘤信号特点的变化,术前肿瘤实质、正常肌肉组织、坏死组织之间ADC值的对比；术后与术前各组织之间ADC值的变化。结果：术前肿瘤组织T1WI呈等信号或稍低信号,T2WI呈明显的高信号,DWI图肿瘤呈高信号；相同b值ADC(肿瘤实质)<ADC(正常肌肉组织)<ADC(坏死组织)(p<0.05)：而随着b值的增大,各组织的ADC值减小；术后肿瘤组织DWI仍呈高信号,但较术前为低；术后第1、7、10天肿瘤实质的ADC值均较术前增高(p<0.05),且ADC(术后1天)<ADC(术后10天)(p<0.05)。结论：磁共振弥散加权成像用来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效有意义,治疗早期灭活的肿瘤实质的ADC值即出现变化。第三部分T2*首过灌注加权成像评价无水乙醇消融治疗兔软组织VX2肿瘤疗效的实验研究目的：利用磁共振灌注加权成像(PWI)来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效。材料和方法：15只新西兰大白兔,雌雄不限,体重2.5-3kg,在其右侧大腿内侧注射VX2肿瘤组织悬浮液各约0.2ml,制备成荷瘤兔,于肿瘤组织接种后第14天行常规磁共振扫描,再经耳缘静脉注入Gd-DTPA (0.2ml/kg),注射速率为1.5ml/s。行GRE-EPI序列的T2*MR灌注扫描,扫描后第2天在磁共振导引及监视下行无水乙醇瘤内注射消融治疗。消融治疗后分别于第7、10天再行常规磁共振扫描及PWI扫描,扫描参数与术前一致。观察术前与术后肿瘤信号特点的变化,术前肿瘤实质与正常肌肉组织时间信号曲线的变化；灌注参数值：负性增强分数(NEI)和最大下降斜率(MSD)的对比；术后7天、10天肿瘤中心灭活组织与术前肿瘤实质时间信号曲线的对比；灌注参数值的对比。结果：术前肿瘤组织T1WI呈等信号或稍低信号,T2WI呈明显的高信号,时间信号曲线图(time in tensity curve,TIC)显示肿瘤组织的信号强度在对比剂首过时迅速降低。正常肌肉组织的TIC则变化较平缓。PEI术后第7、10天,肿瘤中心的灭活组织的TIC显示信号强度在对比剂首过时缓慢降低,但比正常肌肉组织下降明显。术前肿瘤组织的NEI及MSD(1145.53士69.79,536.69士17.69)较正常肌肉(763.26士72.57,355.24±25.58)大(P<0.05),术后7天、10天肿瘤中心灭活组织的NEI及MSD较术前均降低,差异有统计学意义(P<0.05)。结论：磁共振灌注加权成像用来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效有意义,治疗早期肿瘤实质的灌注参数就出现变化。第四部分：磁共振氢质子波谱评价无水乙醇消融治疗兔软组织VX2肿瘤疗效的实验研究目的：利用磁共振氢质子波谱(1H-MRS)来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效。材料和方法：15只新西兰大白兔,雌雄不限,体重2.5-3kg,在其右侧大腿内侧注射VX2肿瘤组织悬浮液各约0.2ml,制备成荷瘤兔,于肿瘤组织接种后第14天行常规磁共振扫描,及氢质子波谱成像扫描,采用单体素(SVS)点分辨表面定位序列(PRESS)扫描,TR/TE:1500/144, NEX:8次。扫描后第2天在磁共振导引及监视下行无水乙醇注射消融治疗。消融治疗后分别于第7、10天再行常规磁共振扫描及MRS扫描,扫描参数与术前一致。观察磁共振常规扫描术前与术后肿瘤信号特点的变化；术前与术后MRS波谱扫描谱线的质量、特点分析；比较术前与术后Cho/Lipid峰高值和峰下面积的比值,将扫描所得的数据利用机器自带的functool功能软件在磁共振扫描仪上进行分析,利用SPSS17.0软件包进行统计分析。结果：术前肿瘤组织呈等信号或稍低信号(T1WI)和明显的高信号(T2WI),术前肿瘤组织Cho峰为第一高峰,Lipid峰为第二高峰,Cr峰为最小峰；而术后消融坏死的肿瘤组织Lipid峰变为第一高峰,Cho峰较术前明显下降而成为第二高峰,Cr峰还是最小峰；术前Cho/Lipid峰高值的比值为1.2539±0.3537,峰下面积的比值为1.1357±0.2684;术后7天和10天Cho/Lipid峰高值的比值分别为0.3027±0.1132,0.3125±0.1087；峰下面积的比值分别为0.2589±0.1086,0.2673±0.1145。术后Cho/Lipid峰高值和峰下面积的比值较术前均明显降低,两者比较差异有统计学意义(P<0.05)。结论：磁共振氢质子波谱用来评价无水乙醇消融治疗兔软组织VX2肿瘤的疗效有意义,治疗早期肿瘤实质的Cho峰较术前明显下降,Cho/Lipid峰高值和峰下面积的比值较术前明显降低。更多还原

【Abstract】 Part Ⅰ Establishment of Rabbit VX2Soft Tissue Tumor Model and Treatment with Percutaneous Ethanol Injection under the Guidance of Magnetic Resonance ImagingObjective:Establish rabbit VX2soft tissue tumor model,and treat it with percutaneous ethanol injection under the guidance of magnetic resonance imaging.To make ready for the therapeutic evaluation with functional magnetic resonance imaging.Methods and Materials:Fifteen healthy New Zealand white rabbits were included in this study.0.2ml tumor tissue suspensions were injected into the proximate of rabbit posterior limb.14days later, all the rabbits underwent conventional MRI examination.Percutaneous ethanol injection were performed to all the tumors under the guidance of MR in the next day of the examination.T2WI was used as guidance and monitoring means. MR compatible puncture needle with lateral hole was stabed into the lesion center, and injected anhydrous ethanol according to the volume of1ml/cm tumor diameter slowly. To observe the tumors signal characteristics, morphological feature and pathological feature pre-operation and post-operation. Results:All of the15rabbits were established soft tissue tumor model successfully, the success rate is100%. The tumors were oval or round,3-4cm in diam. MRI scanning showed a low signal of the tumor on T1WI and a high signal of the tumor on T2WI before PEI. Percutaneous ethanol injection were performed to all the tumors under the guidance of MR successfully with3.5ml ethanol injected into the tumors.T2WI could monitor the ethanol in dispersion and distribution within the tumors clearly.Histologically, tumors were composed of large, uniform, oval/round cells arranged in solid nests which was intensive in the periphery of tumors. Necrosis was apparent in the center of the tumors.10days after operation, most tissue in the periphery of tumors was coagulative necrosis, only a few tumor cells were residual. Necrosis range in the tumors center were obviously increased compared with preoperative.Conclusion:Rabbit VX2tumor of soft tissue model is suitable for the therapeutic evaluation of tumor.It is an animal model of operation simple and high rate of successful. MR T2WI can monitor the ethanol in dispersion and distribution within the tumors clearly. It is a good guidance and monitoring imaging methods of tumor ablation. Part II The Experimental Study on Diffusion-Weighted Imaging in The Evaluation of Percutaneous Ethanol Injection Therapy Response of Rabbit Soft Tissue VX2TumorObjective:To evaluate the therapy value of percutaneous ethanol injection inVX2soft tissue tumor in the posterior limb of rabbit with Diffusion-Weighted Imaging.Methods and Materials:Fifteen healthy New Zealand white rabbits were included in this study.0.2ml tumor tissue suspensions were injected into the proximate of rabbit posterior limb.All the rabbits underwent conventional MRI and DWI examination after2weeks, with the b values at300,500,700,900s/mm2. Percutaneous ethanol injection were performed to all the tumors under the guidance of MR in the next day of the examination. Conventional MRI and DWI examination were performed to all the rabbits after1、7、10days of PEI. To observe the tumors signal characteristics pre-operation and post-operation, and the ADC values change of the tumor essence, necrotic tissue and normal muscle tissue.Results:MRI scanning showed a low signal of the tumor on T1WI and a high signal of the tumor on T2WI and DWI before PEI. Along with the increased b values,the ADC values of tumor essence, necrotic tissue and normal muscle tissue decreased. There was significant difference between the ADC values of the tumor essence, necrotic tissue and normal muscle tissue under the same b value. The ADC values of tumor essence was smaller than those of the muscle and necrosis tissues. The ADC values of tumor essence had significant statistical difference between pre-PEI therapy and post-PEI therapy on the spots of one,seven and ten days. The signal of tumor essence was lower on DWI than pre-PEI on the spot of10days after therapy.Conclusion:It is possible to apply diffusion-weighted MR imaging to evaluate the PEI therapy value of VX2soft tissue tumor in the posterior limb of rabbit.The ADC values change markedly at the prophase after PEI therapy. Part III The Experimental Study on T2*First Perfusion Weighted Imaging in The Evaluation of Percutaneous Ethanol Injection Therapy Response of Rabbit Soft Tissue VX2TumorObjective:To evaluate the therapy value of percutaneous ethanol injection in VX2soft tissue tumor in the posterior limb of rabbit with T2*first perfusion weighted imaging.Methods and Materials:Fifteen healthy New Zealand white rabbits were included in this study.0.2ml tumor tissue suspensions were injected into the proximate of rabbit posterior limb. after2weeks, All the rabbits underwent conventional MRI and PWI examination with GD-DTPA injected into the rabbits’ear marginal vein(0.2ml/kg,1.5ml/s). Percutaneous ethanol injection were performed to all the tumors under the guidance of MR in the next day of the examination. Conventional MRI and PWI examinations were performed to all the rabbits after7、10days of PEI.To observe the tumors signal characteristics pre-operation and post-operation, to contrast the time in tensity curve (TIC) of tumor with normal muscle tissue preoperative and postoperative, to calculate the perfusion parameter values of pre-operation and post-operation:negative enhancement integral (NEI) and maximum slope of decrease (MSD).Results:MRI scanning showed a low signal of the tumor on T1WI and a high signal on T2WI before PEI.The tumor’s TIC shows that it’s signal was decreased quickly in the first phase,but the normal muscle tissue’s TIC is flat. After7and10days of PEI,the tumor’s TIC was changed to flat than pre-operation. The tumor’s NEI and MSD (1145.53±69.79,1145.53±17.69) were larger than normal muscle’s (763.26±72.57,763.26±25.58)(P<0.05).7and10days after operation, NEI and MSD of tumor were lower than that of before operation, the difference was statistically significant (P<0.05).ConcIusion:It is possible to apply T2*first perfusion weighted imaging to evaluate the PEI therapy value of VX2soft tissue tumor in the posterior limb of rabbit.The perfusion parameter values change markedly at the prophase after PEI therapy. Part IV The Experimental Study on1H-MRS in The Evaluation of Percutaneous Ethanol Injection Therapy Response of Rabbit Soft Tissue VX2’TumorObjective:To evaluate the therapy value of percutaneous ethanol injection in VX2soft tissue tumor in the posterior limb of rabbit with1H-MRS.Methods and Materials:Fifteen healthy New Zealand white rabbits were included in this study.0.2ml tumor tissue suspensions were injected into the proximate of rabbit posterior limb. after2weeks, All the rabbits underwent conventional MRI and1H-MRS(TR/TE:1500/144, NEX:8) examination.Percutaneous ethanol injection were performed to all the tumors under the guidance of MR in the next day of the examination. Conventional MRI and1H-MRS examinations were performed to all the rabbits after7、10days of PEI. To observe the tumors signal characteristics pre-operation and post-operation, to analysis the tumors’MRS spectrum characteristics preoperative and postoperative, to calculate the Cho/Lipid peak value before operation and after operation.Statistical analysis was used with SPSS17.Results:MRI scanning showed a low signal of the tumor on T1WI and a high signal of the tumor on T2WI before PEI. Before operation, Cho peak(3.2ppm) of the tumor was the first peak, Lipid peak(1.4ppm) was the second peak and Cr peak(3.02ppm) was minimum; However, after operation, the Lipid peak changed into the first peak, Cho peak went down and became the second peak. Cho/Lipid values of pre-operation (1.2539±0.3537,1.1357±0.2684) were higher than those of post-operation(0.3027±0.1132,0.2589±0.1086;0.3125±0.1087,0.2673±0.1145).the difference was statistically significant (P<0.05).Conclusion:It is possible to apply1H-MRS to evaluate the PEI therapy value of VX2soft tissue tumor in the posterior limb of rabbit. Cho peak decreased obviously and Cho/Lipid values were significantly lower than pre-operation at the prophase after PEI therapy.更多还原