同步辐射技术检测肝细胞癌新生血管的实验研究
发布时间：2018-07-17 06:24
【摘要】：第一部分 同步辐射成像技术应用于裸鼠肝细胞癌新生血管的实验研究 目的：应用同步辐射微血管造影技术进行裸鼠离体肝细胞癌肿瘤新生血管的形态学研究。 方法：建立高转移人肝癌细胞HCCLM3-RFP裸鼠肝脏移植瘤模型。肝脏移植瘤模型建立第1、2、3、4周,各取模型数3只,经腹腔内注射戊巴比妥钠麻醉后开腹,经下腔静脉留置管,手动推注生理盐水,置换肝脏血液,结扎肝脏的血管和胆管后切除肝脏。第4周,取模型鼠3只,经腹腔内注射戊巴比妥钠麻醉后开腹,经下腔静脉留置管,手动推注硫酸钡悬浮液,直至肝脏及肝肿瘤表面血管呈白色,结扎肝脏的血管和胆管后切除肝脏。所有标本均浸泡在福尔马林溶液里,准备成像。离体裸鼠肝癌新生血管成像在上海光源(SSRF)X射线成像与生物医学应用光束线站(BL13W)进行。 结果：同步辐射微血管造影结合显微断层成像(CT)获得了高质量的肿瘤新生血管图像。图像显示正常肝血管结构被迅速生长的肿瘤组织取代,可以清晰观察到肿瘤新生血管的形态特征及生长状况能清楚反映肿瘤新生血管的分布和形态,其特征为：分布杂乱无章；形态无规则,局部可见树枝状分支；个别血管异常弯曲,构成成簇的细小血管网络结构；可见大量无血管区域。能分辨肿瘤内部最细的血管直径约20μm左右。从血管密度统计结果分析,第2周时肿瘤微血管密度达到最大,约4.58%,以后肿瘤体积增速明显升高,达到最大增速,但微血管密度明显下降。 结论：采用生理盐水、硫酸钡作为造影剂,利用同步辐射微血管造影技术显示裸鼠肝肿瘤新生血管的方法可行。 第二部分 同步辐射类同轴相位衬度成像技术检测人肝细胞癌新生血管的实验研究 目的：通过同步辐射类同轴相衬成像(in-line phase contrast imaging,IL-PCI)技术进行离体人肝细胞癌(hepatocellular carcinoma,HCC)标本新生血管的形态学初步研究。 方法：选用2011年6月至2011年10月复旦大学附属中山医院肝外科手术切除的HCC标本4例。术前肝脏未注射任何造影剂,术后离体肝癌标本浸泡在福尔马林溶液里,准备成像。离体人HCC新生血管成像在上海光源(SSRF)X射线成像与生物医学应用光束线站(BL13W)进行。 结果：IL-PCI结合显微CT获得了高质量的肿瘤新生血管图像,可以清楚观察到肿瘤边界和肿瘤新生血管,能分辨血管的最小直径约10μm。重建后得到的三维立体图像更清晰,能清楚反映肿瘤新生血管的分布和形态,其特征为：分布杂乱无章；形态无规则,局部可见树枝状分支；个别血管异常弯曲,构成成簇的细小血管网络结构；可见大量无血管区域。 结论：通过IL-PCI技术可以成功获得无造影剂条件下人HCC标本肿瘤新生血管显像图像。 第三部分 同步辐射衍射增强成像技术检测人肝细胞癌新生血管的实验研究 目的：通过同步辐射衍射增强成像技术(diffraction enhanced imaging,DEI)进行离体人肝细胞癌(hepatocellular carcinoma,HCC)标本新生血管的形态学初步研究。 方法：选用2011年6月至2011年10月复旦大学附属中山医院肝外科手术切除的HCC标本4例。术前肝脏未注射任何造影剂,术后离体肝癌标本浸泡在福尔马林溶液里,准备成像。离体人HCC新生血管成像在试验在北京高能物理研究所同步辐射国家试验室(BSRF)的形貌站(4W1A)进行。 结果：DEI获得了高质量的肿瘤新生血管图像,可以清楚观察到肿瘤边界、肿瘤新生血管和癌巢结节样结构。肿瘤新生血管分布杂乱无章,形态无规则,能分辨肿瘤血管的最小直径约25μm。 结论：通过DEI技术可以成功获得无造影剂条件下人HCC标本肿瘤新生血管显像图像。
[Abstract]:Part one
Experimental study of synchrotron radiation imaging in hepatocellular carcinoma of nude mice
Objective: To study the morphology of tumor angiogenesis in nude mice with hepatocellular carcinoma by synchrotron radiation microangiography.
Methods: the liver transplantation tumor model of high metastatic human hepatoma cell HCCLM3-RFP was established. The liver transplantation tumor model was established at week 1,2,3,4. The number of each model was 3. After intraperitoneal injection of pentobarbital sodium, the liver transplanted tumor was injected into the inferior vena cava, the normal saline was injected manually, the liver blood was replaced, the liver blood vessels and bile duct were ligated and the liver was removed. Fourth weeks, 3 rats were taken from the model rats by intraperitoneal injection of pentobarbital sodium and anaesthetized by sodium pentobarbital. The barium sulfate suspension was manually injected through the inferior vena cava, until the liver and liver tumor surfaces were white. The liver was ligated and the liver was ligated. All specimens were immersed in the formalin solution to prepare imaging. In vitro nude mice. Hepatocellular carcinoma (SSRF) X ray imaging and biomedical application beamline station (BL13W) were performed on hepatocellular carcinoma (X).
Results: high quality neovascularization images were obtained by synchrotron radiation microangiography and microtomography (CT). The images showed that the normal hepatic vascular structure was replaced by the rapidly growing tumor tissue. The morphological characteristics and growth status of the neovascularization of the tumor could be clearly observed and the distribution and shape of the neovascularization of tumor could be clearly reflected. State, characterized by disorderly distribution, irregular shape, locally visible branches of branches, abnormal curvature of individual blood vessels to form a small vascular network structure, and a large number of vascular areas, which can be seen in a large number of vascular areas. The diameter of the finest vessels within the tumor is about 20 m. The tumor microvessels are analyzed at second weeks from the statistical results of blood vessel density. The density reached the maximum, about 4.58%. After that, the tumor volume increased significantly and reached the maximum growth rate, but the microvessel density decreased significantly.
Conclusion: using normal saline and barium sulfate as contrast medium, it is feasible to use synchrotron radiation microangiography to detect neovascularization of liver tumor in nude mice.
The second part
Synchrotron radiation coaxial phase contrast imaging for detection of neovascularization in human hepatocellular carcinoma
Objective: To study the morphology of the neovascularization of the isolated human hepatocellular carcinoma (hepatocellular carcinoma, HCC) specimens by in-line phase contrast imaging (IL-PCI).
Methods: 4 HCC specimens from the liver surgery of Zhongshan Hospital Affiliated to Fudan University from June 2011 to October 2011 were selected. The liver specimens were soaked in the formalin solution before operation without any contrast medium. The imaging of the isolated human HCC neovascularization in the Shanghai light source (SSRF) X ray imaging and biomedical application The beam line station (BL13W) is carried out.
Results: IL-PCI combined with microscopical CT to obtain high quality neovascularization images of tumor, which can clearly observe the tumor boundary and neovascularization, and can distinguish the minimum diameter of the vessel with the minimum diameter of about 10 u M., which can clearly reflect the distribution and morphology of the neovascularization of the tumor. There are irregular branches, partial branches of branches, abnormal curved vessels, and clusters of tiny vascular network structures.
Conclusion: tumor angiogenesis images of human HCC specimens without contrast agent can be successfully obtained by IL-PCI technology.
The third part
Detection of neovascularization in human hepatocellular carcinoma by synchrotron radiation diffraction enhanced imaging
Objective: To study the morphology of the neovascularization of the isolated human hepatocellular carcinoma (hepatocellular carcinoma, HCC) specimens by synchrotron radiation diffraction enhanced imaging (diffraction enhanced imaging, DEI).
Methods: 4 HCC specimens from the liver surgery of Zhongshan Hospital Affiliated to Fudan University from June 2011 to October 2011 were selected. The liver specimens were soaked in formalin solution and prepared for imaging before operation. The imaging of isolated human HCC neovascularization was performed at the synchronous radiation country of Beijing High Energy Institute of physics. The morphology station (4W1A) of the home test room (BSRF) was carried out.
Results: DEI obtained a high quality neovascular image of neovascularization. It can clearly observe the tumor boundary, neovascularization and nodular structure of the tumor nest. The neovascularization of the tumor is irregular and irregular in shape, and can distinguish the minimum diameter of the tumor vessel about 25 u m..
Conclusion: tumor angiogenesis images of human HCC specimens without contrast agent can be successfully obtained by DEI technology.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R735.7;R730.44
本文编号：2129389
[Abstract]:Part one
Experimental study of synchrotron radiation imaging in hepatocellular carcinoma of nude mice
Objective: To study the morphology of tumor angiogenesis in nude mice with hepatocellular carcinoma by synchrotron radiation microangiography.
Methods: the liver transplantation tumor model of high metastatic human hepatoma cell HCCLM3-RFP was established. The liver transplantation tumor model was established at week 1,2,3,4. The number of each model was 3. After intraperitoneal injection of pentobarbital sodium, the liver transplanted tumor was injected into the inferior vena cava, the normal saline was injected manually, the liver blood was replaced, the liver blood vessels and bile duct were ligated and the liver was removed. Fourth weeks, 3 rats were taken from the model rats by intraperitoneal injection of pentobarbital sodium and anaesthetized by sodium pentobarbital. The barium sulfate suspension was manually injected through the inferior vena cava, until the liver and liver tumor surfaces were white. The liver was ligated and the liver was ligated. All specimens were immersed in the formalin solution to prepare imaging. In vitro nude mice. Hepatocellular carcinoma (SSRF) X ray imaging and biomedical application beamline station (BL13W) were performed on hepatocellular carcinoma (X).
Results: high quality neovascularization images were obtained by synchrotron radiation microangiography and microtomography (CT). The images showed that the normal hepatic vascular structure was replaced by the rapidly growing tumor tissue. The morphological characteristics and growth status of the neovascularization of the tumor could be clearly observed and the distribution and shape of the neovascularization of tumor could be clearly reflected. State, characterized by disorderly distribution, irregular shape, locally visible branches of branches, abnormal curvature of individual blood vessels to form a small vascular network structure, and a large number of vascular areas, which can be seen in a large number of vascular areas. The diameter of the finest vessels within the tumor is about 20 m. The tumor microvessels are analyzed at second weeks from the statistical results of blood vessel density. The density reached the maximum, about 4.58%. After that, the tumor volume increased significantly and reached the maximum growth rate, but the microvessel density decreased significantly.
Conclusion: using normal saline and barium sulfate as contrast medium, it is feasible to use synchrotron radiation microangiography to detect neovascularization of liver tumor in nude mice.
The second part
Synchrotron radiation coaxial phase contrast imaging for detection of neovascularization in human hepatocellular carcinoma
Objective: To study the morphology of the neovascularization of the isolated human hepatocellular carcinoma (hepatocellular carcinoma, HCC) specimens by in-line phase contrast imaging (IL-PCI).
Methods: 4 HCC specimens from the liver surgery of Zhongshan Hospital Affiliated to Fudan University from June 2011 to October 2011 were selected. The liver specimens were soaked in the formalin solution before operation without any contrast medium. The imaging of the isolated human HCC neovascularization in the Shanghai light source (SSRF) X ray imaging and biomedical application The beam line station (BL13W) is carried out.
Results: IL-PCI combined with microscopical CT to obtain high quality neovascularization images of tumor, which can clearly observe the tumor boundary and neovascularization, and can distinguish the minimum diameter of the vessel with the minimum diameter of about 10 u M., which can clearly reflect the distribution and morphology of the neovascularization of the tumor. There are irregular branches, partial branches of branches, abnormal curved vessels, and clusters of tiny vascular network structures.
Conclusion: tumor angiogenesis images of human HCC specimens without contrast agent can be successfully obtained by IL-PCI technology.
The third part
Detection of neovascularization in human hepatocellular carcinoma by synchrotron radiation diffraction enhanced imaging
Objective: To study the morphology of the neovascularization of the isolated human hepatocellular carcinoma (hepatocellular carcinoma, HCC) specimens by synchrotron radiation diffraction enhanced imaging (diffraction enhanced imaging, DEI).
Methods: 4 HCC specimens from the liver surgery of Zhongshan Hospital Affiliated to Fudan University from June 2011 to October 2011 were selected. The liver specimens were soaked in formalin solution and prepared for imaging before operation. The imaging of isolated human HCC neovascularization was performed at the synchronous radiation country of Beijing High Energy Institute of physics. The morphology station (4W1A) of the home test room (BSRF) was carried out.
Results: DEI obtained a high quality neovascular image of neovascularization. It can clearly observe the tumor boundary, neovascularization and nodular structure of the tumor nest. The neovascularization of the tumor is irregular and irregular in shape, and can distinguish the minimum diameter of the tumor vessel about 25 u m..
Conclusion: tumor angiogenesis images of human HCC specimens without contrast agent can be successfully obtained by DEI technology.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R735.7;R730.44
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