基于同步輻射CT成像的乳腺癌微血管的定量研究
發(fā)布時(shí)間：2018-12-16 05:07
【摘要】：腫瘤新生血管對(duì)惡性腫瘤的發(fā)生、發(fā)展和轉(zhuǎn)移具有重要作用,腫瘤微血管網(wǎng)絡(luò)的形態(tài)結(jié)構(gòu)也反映著腫瘤的生長狀態(tài)。而目前醫(yī)療領(lǐng)域所使用的成像方法,如CT、MRI、超聲,僅能分辨100微米以上的血管,無法觀察到腫瘤新生血管,給腫瘤的早期診斷帶來了很大的困難。同步輻射光源作為新興的成像手段,有著高強(qiáng)度、高耀度等優(yōu)勢(shì),分辨率較傳統(tǒng)成像方法有了近千倍的提高。microfil作為研究微循環(huán)的常用造影劑,能夠分辨直徑20微米以下的血管(Michael Marxen et al., 2003),二者的結(jié)合解決了傳統(tǒng)影像技術(shù)分辨率不足的問題,為腫瘤新生血管結(jié)構(gòu)的精確定量提供可能。 本研究基于4T1乳腺癌的BALB/c雌鼠模型,利用microfil作為腫瘤微血管造影劑,在上海光源生物醫(yī)學(xué)成像線站13W進(jìn)行離體腫瘤樣本的CT成像,獲取不同時(shí)間點(diǎn)的腫瘤微血管數(shù)據(jù)(2GB~5GB),使用常規(guī)的濾波反投影算法進(jìn)行重建后體繪制,觀測(cè)腫瘤微血管形態(tài)的變化趨勢(shì)。另外,本文提出了針對(duì)本課題大數(shù)據(jù)量的腫瘤血管的分塊加載的雙閾值分割方法。為了研究血管生長與生長區(qū)域的關(guān)系,將腫瘤按離中心點(diǎn)的距離進(jìn)行分區(qū),由外到內(nèi)依次為外圍區(qū)域、過渡區(qū)域和中心區(qū)域。結(jié)果表明,利用同步輻射CT造影成像能夠觀察到直徑為20微米左右的腫瘤新生血管;由血管密度和分形維度的統(tǒng)計(jì)結(jié)果來看,惡性腫瘤生長演變迅速,在急劇增殖不久后便迅速壞死、轉(zhuǎn)移,且這一轉(zhuǎn)折點(diǎn)出現(xiàn)在第25天。25天以前腫瘤微血管較少,腫瘤細(xì)胞增殖速度較小;25天腫瘤微血管密度達(dá)到最大,由分形維度反映出的復(fù)雜度也最大;25天以后腫瘤體積增速明顯升高,達(dá)到最大增速,但微血管密度明顯下降,且伴有肺部和淋巴系統(tǒng)的轉(zhuǎn)移。實(shí)驗(yàn)結(jié)果反映出新生血管對(duì)于腫瘤生長、轉(zhuǎn)移的預(yù)示作用。雖然微血管密度的變化趨勢(shì)與分形維度吻合,然而由于腫瘤微血管分布的不均勻性,導(dǎo)致分區(qū)后的微血管密度的統(tǒng)計(jì)存在較大方差,使得其可信度大大降低。由此也反映出微血管密度的測(cè)定與采樣區(qū)域密切相關(guān),因此其客觀性和穩(wěn)定性不及分形維度。 研究結(jié)果表明利用同步輻射光源觀察腫瘤微血管的實(shí)驗(yàn)方法和自主設(shè)計(jì)的分塊加載的雙閾值分割方法具有可行性,分形維度對(duì)于腫瘤微血管定量研究具有重要作用。在今后的研究中,我們將進(jìn)一步優(yōu)化分區(qū),拓展分形維度在腫瘤微血管定量中的運(yùn)用。
[Abstract]:Tumor neovascularization plays an important role in the occurrence, development and metastasis of malignant tumors, and the morphological structure of tumor microvascular network also reflects the growth state of tumor. At present, the imaging methods used in the medical field, such as CT,MRI, ultrasound, can only distinguish more than 100 microns of blood vessels, and can not observe tumor neovascularization, which brings great difficulties to the early diagnosis of tumor. As a new imaging method, synchrotron radiation source has many advantages such as high intensity, high flare and so on. The resolution of synchrotron radiation light source is nearly a thousand times higher than that of traditional imaging method. Microfil is used as a contrast medium to study microcirculation. The combination of (Michael Marxen et al., 2003 with diameter less than 20 渭 m solves the problem of insufficient resolution of traditional image technology and provides the possibility for accurate quantification of tumor neovascularization. In this study, based on the BALB/c female model of 4T1 breast cancer, microfil was used as tumor microvessel contrast medium to perform CT imaging of isolated tumor samples at 13 W of Shanghai Light Source Biomedical Imaging Line Station. The tumor microvessel data (2GB~5GB) at different time points were obtained, and then reconstructed by conventional filtering back-projection algorithm, and the trend of tumor microvessel morphology was observed. In addition, this paper proposes a double threshold segmentation method for tumor vessels with large amount of data. In order to study the relationship between angiogenesis and growth region, the tumor was divided according to the distance from the center to the center, and the outer region, the transitional region and the central region were sequentially divided from outer to inner. The results showed that tumor neovascularization with diameter of 20 渭 m could be observed by synchrotron radiation (CT) imaging. According to the statistical results of vascular density and fractal dimension, malignant tumors grow rapidly, necrosis and metastasis occur soon after rapid proliferation, and this turning point appears on the 25th day. The proliferation rate of tumor cells was small; The tumor microvessel density reached the maximum at 25 days, and the complexity reflected by fractal dimension was the largest. After 25 days, the tumor volume growth rate increased significantly, reached the maximum growth rate, but the microvessel density decreased significantly, and accompanied by lung and lymphatic system metastasis. The results reflect the predictive effect of neovascularization on tumor growth and metastasis. Although the variation trend of microvessel density is consistent with fractal dimension, the statistical variance of microvessel density after partition exists because of the non-uniformity of tumor microvessel distribution, which greatly reduces the reliability of microvessel density. It also shows that the measurement of microvessel density is closely related to the sampling area, so its objectivity and stability are not as good as fractal dimension. The results show that the experimental method of using synchrotron radiation light source to observe tumor microvessels and the self-designed dual-threshold segmentation method with block loading are feasible. Fractal dimension plays an important role in quantitative study of tumor microvessels. In the future research, we will further optimize the partition and expand the application of fractal dimension in tumor microvessel quantification.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R737.9;R318
[Abstract]:Tumor neovascularization plays an important role in the occurrence, development and metastasis of malignant tumors, and the morphological structure of tumor microvascular network also reflects the growth state of tumor. At present, the imaging methods used in the medical field, such as CT,MRI, ultrasound, can only distinguish more than 100 microns of blood vessels, and can not observe tumor neovascularization, which brings great difficulties to the early diagnosis of tumor. As a new imaging method, synchrotron radiation source has many advantages such as high intensity, high flare and so on. The resolution of synchrotron radiation light source is nearly a thousand times higher than that of traditional imaging method. Microfil is used as a contrast medium to study microcirculation. The combination of (Michael Marxen et al., 2003 with diameter less than 20 渭 m solves the problem of insufficient resolution of traditional image technology and provides the possibility for accurate quantification of tumor neovascularization. In this study, based on the BALB/c female model of 4T1 breast cancer, microfil was used as tumor microvessel contrast medium to perform CT imaging of isolated tumor samples at 13 W of Shanghai Light Source Biomedical Imaging Line Station. The tumor microvessel data (2GB~5GB) at different time points were obtained, and then reconstructed by conventional filtering back-projection algorithm, and the trend of tumor microvessel morphology was observed. In addition, this paper proposes a double threshold segmentation method for tumor vessels with large amount of data. In order to study the relationship between angiogenesis and growth region, the tumor was divided according to the distance from the center to the center, and the outer region, the transitional region and the central region were sequentially divided from outer to inner. The results showed that tumor neovascularization with diameter of 20 渭 m could be observed by synchrotron radiation (CT) imaging. According to the statistical results of vascular density and fractal dimension, malignant tumors grow rapidly, necrosis and metastasis occur soon after rapid proliferation, and this turning point appears on the 25th day. The proliferation rate of tumor cells was small; The tumor microvessel density reached the maximum at 25 days, and the complexity reflected by fractal dimension was the largest. After 25 days, the tumor volume growth rate increased significantly, reached the maximum growth rate, but the microvessel density decreased significantly, and accompanied by lung and lymphatic system metastasis. The results reflect the predictive effect of neovascularization on tumor growth and metastasis. Although the variation trend of microvessel density is consistent with fractal dimension, the statistical variance of microvessel density after partition exists because of the non-uniformity of tumor microvessel distribution, which greatly reduces the reliability of microvessel density. It also shows that the measurement of microvessel density is closely related to the sampling area, so its objectivity and stability are not as good as fractal dimension. The results show that the experimental method of using synchrotron radiation light source to observe tumor microvessels and the self-designed dual-threshold segmentation method with block loading are feasible. Fractal dimension plays an important role in quantitative study of tumor microvessels. In the future research, we will further optimize the partition and expand the application of fractal dimension in tumor microvessel quantification.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R737.9;R318
【共引文獻(xiàn)】
相關(guān)期刊論文 前10條
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