A Quantitative Study Of Microvessels Of Breast Cancer Using Sychrotron Radiation

Since tumor angiogenesis has an significant impact on the initiation, development and metastasis of malignant tumors, it is supposed the morphological structure of tumor microvessel network reflects growth status of tumor. Nevertheless, conventional angiography such as CT, MRI and ultrasound cannot depict vessels with diameters of less than 100μm which means tumor angiogenesis cannot be visualized, thus it is very difficult for early diagnosis of tumor. As a promising imaging facility, synchrotron radiation owns some excellent attributes such as high intensity and high brilliance resulting in nearly a thousand-fold increase in resolution. Microfil is frequently used in microcirculation researches as contrast medium and capable of visualizing vessels with diameters of less than 20μm. Therefore, the insufficient resolution problem can be solved by combining microfil contrast medium with synchrotron radiation and it becomes possible to precisely quantify the vascular architecture of tumor.In this study, the digital data(2GB~5GB) of tumor microvessels at different time points were acquired ex vivo using synchrotron radiation CT imaging at biomedical imaging line station in Shanghai Synchrotron Radiation Facility, SSRF. Then 3D reconstructions were performed in the application of filter back projection(FBP) algorithm, followed by volume rendering allowing for observing development tendency of tumor microvessels'morphology. In addition, a double thresholds method combined with block structure loading has been developed for dealing with large quantities of tumor microvessels data. For the purpose of studying the relationship between vessel development and its location, three areas were divided according to the distance to the center, respectively named the periphery area, the transitional area and the central area from the outside to the inside. Results demonstrated vessels with diameters of around than 20μm could be clearly visualized by Synchrotron Radiation CT imaging combined with contrast agent. Judging from the statistical results of microvessel density and fractal dimension, malignant tumors grew and developed rapidly since local necrosis and metastasis happened soon after tremendous proliferation of cells and angiogenesis and the turning point was day 25. Before day 25, there were less tumor microvessels and tumor cells proliferate slower. At day 25, microvessel density reached the maximum as well as its complexity reflected from fractal dimension. After day 25, an obvious volume increase was observed and growth rate attain the maximum, but there was a noticeable decline in microvessel density, followed along with pulmonary and lymphatic system metastasis. The experiment results showed that angiogenesis was prognostic of tumor growth and metastasis. Although the trends of microvessel density and fractal dimension changes were similar, the credibility of microvessel density was greatly reduced due to large statistical variances resulted from inhomogeneity of tumor microvessels. It also reflected the quantification of microvessel density was closely related to sampling area, thus leading to a lack of objectivity and stability compared with fractal dimension.The research results showed it was feasible to observing tumor microvessels in the application of synchrotron radiation source and segmenting vessels using new designed a double thresholds method combined with block loading structure. Besides, it seemed fractal dimension had great effect on quantitative study of tumor microvessels. For the future, there is a need for better partitioning and expanding the applications of fractal dimension in quantification of tumor microvessels.