title: Longitudinal label-free optical-resolution photoacoustic microscopy of tumor angiogenesis in vivo.
abstract: BACKGROUND
  Optical-resolution photoacoustic microscopy (OR-PAM) is a high-resolution imaging technology capable of label-free imaging of the morphology and functions of the microvasculature in vivo. Previous studies of angiogenesis by OR-PAM were carried out primarily with transgenic mice and the mouse ear model. While important findings have been generated using this approach, the application of OR-PAM to the more widely used subcutaneous dorsal tumor models remains challenging, largely due to the respiratory and cardiac motion artifacts, as well as the protruding tumor contours.
  
  
  METHODS
  A noninvasive dorsal skin-fold (N-DSF) model, along with adaptive z-scanning and a corresponding experimental protocol, is developed. Mammary carcinoma cells (4T1) were administered subcutaneously to the backs of female BALB/c mice for tumor inoculation. The mice were anesthetized using a mixture of isofluorane and oxygen.
  
  
  RESULTS
  In vivo OR-PAM of angiogenesis with subcutaneous dorsal tumor models in mice has been demonstrated. To test the performance of this method, we have monitored the growth of 4T1 mouse mammary carcinoma in BALB/c mice over a period of 9 days. The major features of tumor angiogenesis, including the change of vascular tortuosity, the dilation of vessel diameters, and the increase of blood supply, have been clearly captured with OR-PAM.
  
  
  CONCLUSIONS
  In combination with N-DSF model, OR-PAM has demonstrated outstanding capacity to provide label-free monitoring of angiogenesis in tumor. Thus, OR-PAM is of great potential to find broad biomedical applications in the pathophysiological studies of tumor and the treatments for anti-angiogenesis.
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Riqiang
authors.initials: R
authors.lastname: Lin
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Huina
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yan
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Song
keywords: Tumor angiogenesis; dorsal skin-fold (DSF); optical resolution photoacoustic microscopy (OR-PAM)