Tumor angiogenesis imaging using an integrated photoacoustic microscopy with hybrid-resolution (Conference Presentation)

Angiogenesis is a key factor for the growth and expansion of malignant tumors. Recently, non-invasive imaging techniques have been largely employed to observe the functional neovascular status of tumor progression. In this study, we present an integrated hybrid-resolution photoacoustic microscopy (PAM) capable of both optical-resolution (OR: a tightly focused beam for finer lateral resolution at shallower region) and acoustic-resolution (AR: a deeper imaging depth based on its ultrasound-dominated detection with relatively large illumination area) imaging for monitoring the progression of angiogenesis. The hybrid-resolution design is achieved by using a liquid lens to adjust the beam size for OR/AR mode selection. A multimode fiber with small core diameter is used to maintain the fine lateral resolution and deliver the laser light with higher energy for OR and AR illumination, respectively. The imaging resolutions of the proposed PAM are demonstrated by phantom experiments: the lateral resolution of OR mode is ~20 μm at a depth of 1 mm, while the resolution of AR mode is ~80 μm at depths of 2 to 3 mm. Additionally, in vivo experiments are conducted to show the capability of this PAM. Angiogenesis imaging of a subcutaneous tumor model in mice is presented using its intrinsic optical contrast (i.e., hemoglobin). Besides, information of oxygen saturation is also acquired using two wavelengths to indicate the hypoxic region of the tumor. In summary, the developed hybrid-resolution PAM is able to monitor the angiogenesis and provide hemodynamic information of tumor covering a broader depth range with high resolutions.