同步輻射技術檢測肝細胞癌新生血管的實驗研究
發(fā)布時間：2018-07-17 06:24
【摘要】：第一部分 同步輻射成像技術應用于裸鼠肝細胞癌新生血管的實驗研究 目的：應用同步輻射微血管造影技術進行裸鼠離體肝細胞癌腫瘤新生血管的形態(tài)學研究。 方法：建立高轉(zhuǎn)移人肝癌細胞HCCLM3-RFP裸鼠肝臟移植瘤模型。肝臟移植瘤模型建立第1、2、3、4周,各取模型數(shù)3只,經(jīng)腹腔內(nèi)注射戊巴比妥鈉麻醉后開腹,經(jīng)下腔靜脈留置管,手動推注生理鹽水,置換肝臟血液,結扎肝臟的血管和膽管后切除肝臟。第4周,取模型鼠3只,經(jīng)腹腔內(nèi)注射戊巴比妥鈉麻醉后開腹,經(jīng)下腔靜脈留置管,手動推注硫酸鋇懸浮液,直至肝臟及肝腫瘤表面血管呈白色,結扎肝臟的血管和膽管后切除肝臟。所有標本均浸泡在福爾馬林溶液里,準備成像。離體裸鼠肝癌新生血管成像在上海光源(SSRF)X射線成像與生物醫(yī)學應用光束線站(BL13W)進行。 結果：同步輻射微血管造影結合顯微斷層成像(CT)獲得了高質(zhì)量的腫瘤新生血管圖像。圖像顯示正常肝血管結構被迅速生長的腫瘤組織取代,可以清晰觀察到腫瘤新生血管的形態(tài)特征及生長狀況能清楚反映腫瘤新生血管的分布和形態(tài),其特征為：分布雜亂無章；形態(tài)無規(guī)則,局部可見樹枝狀分支；個別血管異常彎曲,構成成簇的細小血管網(wǎng)絡結構；可見大量無血管區(qū)域。能分辨腫瘤內(nèi)部最細的血管直徑約20μm左右。從血管密度統(tǒng)計結果分析,第2周時腫瘤微血管密度達到最大,約4.58%,以后腫瘤體積增速明顯升高,達到最大增速,但微血管密度明顯下降。 結論：采用生理鹽水、硫酸鋇作為造影劑,利用同步輻射微血管造影技術顯示裸鼠肝腫瘤新生血管的方法可行。 第二部分 同步輻射類同軸相位襯度成像技術檢測人肝細胞癌新生血管的實驗研究 目的：通過同步輻射類同軸相襯成像(in-line phase contrast imaging,IL-PCI)技術進行離體人肝細胞癌(hepatocellular carcinoma,HCC)標本新生血管的形態(tài)學初步研究。 方法：選用2011年6月至2011年10月復旦大學附屬中山醫(yī)院肝外科手術切除的HCC標本4例。術前肝臟未注射任何造影劑,術后離體肝癌標本浸泡在福爾馬林溶液里,準備成像。離體人HCC新生血管成像在上海光源(SSRF)X射線成像與生物醫(yī)學應用光束線站(BL13W)進行。 結果：IL-PCI結合顯微CT獲得了高質(zhì)量的腫瘤新生血管圖像,可以清楚觀察到腫瘤邊界和腫瘤新生血管,能分辨血管的最小直徑約10μm。重建后得到的三維立體圖像更清晰,能清楚反映腫瘤新生血管的分布和形態(tài),其特征為：分布雜亂無章；形態(tài)無規(guī)則,局部可見樹枝狀分支；個別血管異常彎曲,構成成簇的細小血管網(wǎng)絡結構；可見大量無血管區(qū)域。 結論：通過IL-PCI技術可以成功獲得無造影劑條件下人HCC標本腫瘤新生血管顯像圖像。 第三部分 同步輻射衍射增強成像技術檢測人肝細胞癌新生血管的實驗研究 目的：通過同步輻射衍射增強成像技術(diffraction enhanced imaging,DEI)進行離體人肝細胞癌(hepatocellular carcinoma,HCC)標本新生血管的形態(tài)學初步研究。 方法：選用2011年6月至2011年10月復旦大學附屬中山醫(yī)院肝外科手術切除的HCC標本4例。術前肝臟未注射任何造影劑,術后離體肝癌標本浸泡在福爾馬林溶液里,準備成像。離體人HCC新生血管成像在試驗在北京高能物理研究所同步輻射國家試驗室(BSRF)的形貌站(4W1A)進行。 結果：DEI獲得了高質(zhì)量的腫瘤新生血管圖像,可以清楚觀察到腫瘤邊界、腫瘤新生血管和癌巢結節(jié)樣結構。腫瘤新生血管分布雜亂無章,形態(tài)無規(guī)則,能分辨腫瘤血管的最小直徑約25μm。 結論：通過DEI技術可以成功獲得無造影劑條件下人HCC標本腫瘤新生血管顯像圖像。
[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.
【學位授予單位】：復旦大學
【學位級別】：博士
【學位授予年份】：2013
【分類號】：R735.7;R730.44
本文編號：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.
【學位授予單位】：復旦大學
【學位級別】：博士
【學位授予年份】：2013
【分類號】：R735.7;R730.44
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