Based On Synchrotron Radiation X-ray Microvascular Imaging Studies Of Breast Cancer

Background Breast cancer is one of the most frequent female malignant tumors. Angiogenesis makes an important role in process of solid tumor. Growth and metastasis of solid tumor depends on the formation of new vessels. However, only vessels lager than200μm in diameter can be observed using conventional medical imaging system. And immunohistochemistry has been widely used to measure MVD to get the growth degree of tumor, but it has been limited in generating detailed and reproducible data. Synchrotron Radiation (SR) imaging, whose spatial resolution can reach1μm as the highest, has great advantages in imaging soft tissue structure, such as blood vessels and tumors.Objective To investigate the structures and density of microvessels in xenograft mouse models and to evaluate vascular effects of PEA3gene and therapeutic response of Avastin to microvessels in breast cancer.Methods Barium sulphate nanoparticles were injected into the left cardiac ventricle of the mice, and visualization of blood vessels was studied using Shanghai Synchrotron Radiation Facility (SSRF). Meanwhile, lung metastasis was detected clearly using in-line phase contrast imaging.Results Three-dimensional (3D) structures of microvessels were displayed with a high spatial image resolution of20-30μm using third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. The density of angiogenesis was significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. In addition, the density of smaller vessels (diameter<50μm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter>100μm) was not significantly changed. In addition,3D structures tumor angiogenesis of lung metastasis of breast cancer xenograft mouse models were displayed to evaluate lung metastasis characteristic of PEA3overexpression, and the amount of blood vessels of tumors was increased significantly in tumors expressing high levels of PEA3relative to control groups.Conclusions The above results showed the feasibility of observation of microvessels in tumor using Synchrotron Radiation. The detailed quantitative information obtained from SR-based microangiography indicates a new direction for the application of anti-angiogenic and genetic effect on vessels in basic and clinical cancer research. Thus, SR is a promising new imaging tool for early diagnosis of tumor and therapeutic drug responses.