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术后瘢痕组织和肿瘤复发模型的制备及磁共振成像研究

Preparation and MRI Research of Postsurgery Scar Tissue and Recurrent Tumor Model

【作者】 张海栋

【导师】 王仁法;

【作者基本信息】 华中科技大学 , 影像医学与核医学, 2010, 博士

【摘要】 目的建立术后瘢痕组织病理模型,探讨术后瘢痕组织病理模型的可行性,研究术后瘢痕组织病理模型的病理学表现。材料与方法9只新西兰大白兔,体重2-4kg,采用速眠新Ⅱ肌肉注射麻醉,0.2ml/kg体重。麻醉满意后,对兔子后大腿局部备皮,在无菌环境下,钝性分离并部分离断其后大腿的肌梭,植入折叠后面积大小约3x3cm2的生理盐水浸泡过的无菌纱布,常规消毒后缝合、包扎。术后5天内每天对切口消毒一次,并肌肉注射硫酸庆大霉素2mg/kg体重,防止术后感染。植入纱布后两周,麻醉,在无菌条件下,取出植入的纱布。观察3周后,取瘢痕组织进行病理学检查。对取出的瘢痕组织行大体病理学观察后,制成厚度为5umm的组织切片行H-E染色,在显微镜下观察并进行显微摄影。结果9只兔子术后瘢痕组织的病理模型均制备成功,大体病理学观察,增生斑痕组织大小在1.3-2.6cm范围,表现为以白色为主的淡红色,质地较韧。显微镜下观察,瘢痕组织形态不规则,由增生的成纤维细胞构成,胶原纤维大量沉积,呈条索状或漩涡状分布,一定数量的小血管残存,与人体组织的增生性瘢痕组织表现相似。尚有少量的炎性细胞。结论钝性分离并局部离断肌肉组织,植入无菌纱布刺激瘢痕组织增生是一种制备术后瘢痕组织模型的有效造模方法,制备的瘢痕组织在病理上与人体的增生性瘢痕结构类似。目的研究术后瘢痕组织模型的磁共振表现,对照分析术后瘢痕组织的MRI表现与病理学表现,研究它们的相关性。材料与方法20只新西兰大白兔,在无菌环境下,钝性分离并部分离断其后大腿的肌梭,植入生理盐水浸泡过折叠后面积约3×3cm2的无菌纱布。植入纱布后两周,取出植入的纱布。观察3周后,利用GE Excite 1.5T超导磁共振仪进行磁共振平扫、磁共振弥散加权成像和动态对比增强磁共振成像,扫描完成后,取瘢痕组织进行病理学检查。结果20只兔子瘢痕组织模型均制备成功。镜下观察,瘢痕组织细胞排列紊乱,形态不规则,主要由大量的成纤维细胞、胶原纤威吓一定数量的小血管构成。磁共振平扫,瘢痕组织均表现为以中等信号为主的稍短T1长T2信号,内部信号欠均匀。DWI图上,瘢痕组织呈高信号,在ADC图上,瘢痕组织表现为等信号或稍低信号。b=200s/mm2时瘢痕组织和正常肌肉组织的ADC值差异无统计学意义;在b=400s/mm2和b=600s/mm2时,瘢痕组织和正常肌肉组织的ADC值的差异有统计学意义(P<0.05)。随着b值增加,ADC值有所减小。动态增强扫描,时间-信号强度曲线12例呈缓慢上升型,8例曲线升支较陡直,升至峰值后持续在相对较高水平。瘢痕组织和正常肌肉组织的时间-信号强度曲线有显著性差异。结论术后瘢痕组织的磁共振表现具有良性病变的一些表现,瘢痕组织的磁共振表现在一定程度上可以反应其病理特点。目的制备术后瘢痕组织和肿瘤复发的模型,研究术后瘢痕组织和肿瘤复发的氢质子磁共振波谱表现。材料与方法20只新西兰大白兔,采用速眠新Ⅱ肌肉注射麻醉。麻醉后,取兔子的右后大腿,在无菌环境下,钝性分离并部分离断其后大腿的肌梭,植入折叠后面积大小约3×3cm2的两块生理盐水浸泡过的无菌纱布。在同次手术中,将VX2肿瘤组织混悬液1ml,接种于兔子左后大腿肌肉的肌梭内。术后对切口消毒,并肌肉注射抗生素,以防感染。两周后,在无菌条件下,取出植入的纱布。同次手术中,将肿瘤切除,局部保留少许肿瘤包膜,术后抗感染。取出纱布3周后可触及明显的软组织肿块,后进行磁共振平扫和利用PRESS序列进行单体素1H-MRS采集。磁共振扫描仪采用GE 1.5T Excite磁共振扫描仪,扫描线圈用头线圈或3英寸表面线圈。结果20只兔子术后瘢痕组织和肿瘤复发模型的制备均成功。瘢痕组织形态不规则,大量的成纤维细胞聚集,胶原纤维沉积,一定数量的小血管残存,有少量的炎性细胞浸润。复发的肿瘤组织,瘤细胞呈巢状或不规则弥漫性分布,细胞核大而染色深,异形性明显,瘤间质有大量不成熟的毛细血管和纤维组织。所有兔子正常肌肉组织1H-MRS均表现为Cho峰最小,位于3.2ppm处;Lipid峰最高,位于1.4-1.6ppm处;Cr峰较高,位于3.02ppm处。瘢痕组织中有17例1H-MRS采集成功,表现为在1.4-1.6ppm处均有高大的脂质峰,其中5例在3.2ppm处有小的Cho峰和3.02ppm处有小的Cr峰,12例未见Cho峰和Cr峰。3例扫描不成功。复发的VX2肿瘤在1H-MRS均表现为:Cho峰增高,明显高于肌肉组织;Lipid峰较低,低于正常肌肉组织;Cr峰较低,在谱线上不易辨认或者与Cho峰融合。结论兔子正常肌肉、复发的VX2肿瘤组织和术后增生的瘢痕组织之间的1H-MRS存在一定的差异,这种差异是术后瘢痕组织和复发的肿瘤之间代谢差异的反映,JH-MRS有望用于进行术后瘢痕组织和肿瘤复发的鉴别诊断。目的研究术后瘢痕组织和肿瘤复发模型的磁共振灌注表现,对照分析其磁共振灌注表现和病理学表现,探讨磁共振灌注成像鉴别术后瘢痕组织和肿瘤复发的价值。材料与方法20只新西兰大白兔,体重2-4kg,麻醉后,取兔子的右后大腿,在无菌环境下,钝性分离并部分离断其后大腿的肌梭,植入折叠后面积大小约3×3cm2的两块生理盐水浸泡过的无菌纱布。在同次手术中,将VX2肿瘤组织混悬液1ml,接种于兔子左后大腿的肌梭内。术后注射抗生素防感染。两周后,在无菌条件下,取出植入的纱布。同次手术中,将肿瘤切除,局部保留少许肿瘤包膜,术后抗感染。取出纱布3周后可触及明显的软组织肿块。采用GEExicitel.5T超导磁共振仪,利用3D-FSPGR序列进行动态对比增强磁共振灌注成像。对比剂采用GD-DTPA,比较术后瘢痕组织和复发肿瘤的灌注曲线,计算两者的Emax值和Es值,比较两者的差异。结果20只兔子术后瘢痕组织和肿瘤复发模型均制备成功。瘢痕组织内成纤维细胞聚集,胶原纤维沉积,有一定数量的管壁完整的小血管残存。复发的肿瘤组织,瘤细胞丰富密集,表现为巢状或不规则弥漫性分布,细胞核大染色深,异形性明显,间质内含有大量不成熟的毛细血管和一定量的纤维组织。动态增强扫描11例瘢痕组织的强化曲线呈缓慢上升型,9例瘢痕组织的强化曲线升支快速上升,到达峰值后呈相对平坦的曲线。复发的肿瘤组织的强化曲线7例呈快速上升后又快速下降的曲线,13例呈快速上升后缓慢下降的曲线。瘢痕组织的Emax值为57.63±15.02,Es值为0.62±0.35;肿瘤组织的Emax值为125.26±27.61,Es值为1.38±0.47。两者差异具有统计学意义(p<0.05)。结论术后瘢痕组织和复发的肿瘤MRI灌注曲线有统计学意义的差异,这种差异是两者病理学差异的反映。MRI灌注是鉴别术后瘢痕组织和肿瘤复发的较好方法。

【Abstract】 Objective:To prepare the postoperative scar models and research it’s pathology findings.Methods:Postoperative scar models were made in the hind thigh of 9 New Zealand white rabbits. After anesthetize with Su Mian XinⅡby intramuscular injection, In the sterile environment, we blunt dissected and partly mutilate the hind thigh muscles. Then we folded and packed a asepsis saline sooked gauze of 3cm2 between the muscle bellies. The gentamicin sulfate was used to prevent infection after operation. Two weeks later, the gauze was surgically removed in aseptic conditions. After 3 weeks of observation, we took the scar tissue to do pathology examination and make microphotograph under the microscope.Results:All the 9 postoperative scar models were successful. The size of the scar tissue was about 1.3-2.6cm, The main color was white. Under the microscope, a lot fibroblasts were hyperplasia and collagen fibrils deposited in the scar tissue. In the scar, there was some small vessels remnant and some phlegmasia cells infiltrated. Conclusion:To blunt dissected the muscles and packed gauze between the muscle bellies is a good method to make the postoperative scar models. The pathology appearances of the models were similar to the hyperplastic scar. Objective:To establish experimental animal models of postoperative scar tissue and determine whether MRI and pathology of postoperative scar are associated. Materialand Methods:Postoperative scar models were made in the hind thigh of 20 New Zealand white rabbits. In the sterile environment, we blunt dissected and partly mutilate the post thigh muscles after anesthetize. Then we folded and packed a asepsis saline sooked gauze of 3cm2 between the muscle bellies. The gentamicin sulfate was used to prevent infection after operation. Two weeks later, the gauze was surgically removed in aseptic conditions. After 3 weeks of observation, we used Ge Excite 1.5T superconducting MR device to made plain MRI scanning、DWI and DCE-MRI. We took the scar tissue to do pathology examination after scanning. Results:All the 20 postoperative scar models were successful. Under the microscope, a lot fibroblasts were hyperplasia and collagen fibrils deposited in the scar tissue. In the scar, there was some small vessels remnant. The scar tissue appeared middling T1 and long T2 signal in the plain scanning. On DWI, the scar tissue appeared high signal. On ADC imaging, the scar tissue appeared middle or slightly low signal. When we used b=200s/mm2, the difference of ADC were not statistically significant between the scar and muscle. But at b=400s/mm2 and b=600s/mm2, the difference of ADC were statistically significant between the scar and muscle. On DCE-MRI, the time-signal intensity curve was ascended slowly in 12 cases. In the other 8 cases, the time-signal intensity curve was keeping a relative high level after ascended the maximum intensity. The difference of the time-signal intensity curve was statistically significant between the scar and muscle. Conclusion:The.findings of post operative scar tissue were similar to some benign lesions on MRI. The appearances of post operative scar tissue on MRI were the reflection of their pathology. Objective:Our purpose is to establish experimental animal models of postoperative scar and recurrent tumor, and to investigate in vivo proton magnetic resonance spectroscopy (1H MRS) features of the models. Material and Methods:We used 20 New Zealand white rabbits to establish the models. In the sterile environment, we blunt dissected and partly mutilate the post right thigh muscles of the rabbits after anesthetize. Then we folded and packed two asepsis saline sooked gauzes of 3cm2 between the muscle bellies. At the same time, we implanted with 1ml VX2 tumor tissue suspension in the left proximal thighs. The gentamicin sulfate was used to prevent infection after operation. Two weeks later, the gauzes and the tumor was surgically removed in aseptic conditions. But the peplos of the tumor was remained partly. After 3 weeks of observation, We performed MRI and 1H MRS and analyzed the 1H MRS features of postoperative scar tissue and recurrent VX2 tumors in all rabbits. Results:Twenty models were all successful. A lot fibroblasts were hyperplasia and collagen fibrils deposited in the scar tissue. In the scar, there was some small vessels remnant. In the recurrent tumors, the tumor cells were distributed diffusion or like nests. The nuclear of the recurrent tumor was obviously heteromorphy. Among the interstitial substances of the recurrent tumor, there was a lot of immature vascular hyperplasia. Cho, Cr and lipid peak were seen in the in vivo 1H MRS of normal muscle. The Lip peak was the highest, the Cr was higher, and the Cho was low. The 1H MRS of 17 cases was successfully acquired in the 20 postoperative scar models. Five had the very low Cho and Cr peak of the 17 cases. There were no Cho and Cr in the other 12 cases. The Lip and the Cho peak of all the recurrent tumors were obviously high. But the Cr was low. The Lip was lower than the muscle and the Cho was higher than the muscle. Conclusion:The postoperative scar and recurrent VX2 tumor of rabbits showed great difference in 1H MRS. In vivo 1H MRS may reveal the difference of metabolism information in the postoperative scar and recurrent tumor. Maybe 1H MRS can be used to the differential diagnosis between the postoperative scar tissue and the recurrent tumor. Objective:To study the DCE-MRI findings of the postoperative scar tissue and the recurrent tumor models. Correlate the DCE-MRI findings and the pathology findings of the postoperative scar tissue and recurrent tumor to analysis their associativity. To investigate the differentiation diagnosis value of DCE-MRI in postoperative scar and recurrent tumor.Material and Methods:20 New Zealand white rabbits were used to establish the models. In the sterile environment, we blunt dissected and partly mutilate the post right thigh muscles of the rabbits after anesthetize. Then we folded and packed two asepsis saline sooked gauzes of 3cm2 between the muscle bellies. At the same time, we implanted with lml VX2 tumor tissue suspension in the left proximal thighs. The gentamicin sulfate was used to prevent infection after operation. Two weeks later, the gauzes and the tumor was surgically removed in aseptic conditions. But the capsule of the tumor was remained partly. After 3 weeks of observation, We performed DCE-MRI used 3D-FSPGR series and analyzed the DCE-MRI features of postoperative scar tissue and recurrent VX2 tumors in all rabbits. We used GD-DTPA as the contrast media. To compare the time-signal intensity curve and the Emax, Es value between the postoperative scar tissue and the recurrent tumor.Results:Twenty models were all successful. A lot fibroblasts were hyperplasia and collagen fibrils deposited in the scar tissue. In the scar, there was some small vessels remnant. In the recurrent tumors, the tumor cells were distributed diffusion or like nests. The nuclear of the recurrent tumor was obviously heteromorphy. Among the interstitial substances of the recurrent, there was a lot of immature vascular hyperplasia. The time-intensity curve of scar tissue in 11 rabbits ascended slowly but descended not obvious. In 9 rabbits, The time-signal intensity curve of scar tissue ascended quickly and keep a relative high level after reaching the peak value. The time-signal ntensity curve of recurrent tumor ascended suddenly and descended slowly after reaching the peak value in 13 rabbits. In 7 rabbits, The time-signal intensity curve of recurrent tumor ascended and descended quickly. The Emax and Es value of postoperative scar respectively were 57.63±15.02 and 0.62±0.35. The Emax and Es value of recurrent tumor respectively were 125.26±27.61 and 1.38±0.47.Their difference was statistically significant (p<0.05). Conclusion:The difference of the maximum percentage of enhancement (Emax) and enhancement slope(Es) between postoperative scar tissue and recurrent tumor are all significant. The difference is the reflection of their pathology. MR perfusion weighted imaging may be efficacious method to distinguish postoperative scar tissue and recurrence tumor.

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