Abstract

Abstract Background: Tumor angiogenesis and hypoxia are associated with breast cancer growth and metastasis. Photoacoustic (PA) tomography is an optical imaging technology that visualizes distribution and oxygenation status of hemoglobin with high spatial resolution. Initially we developed a photoacoustic mammography (PAM) having a flat-shaped scanning detector that could detect breast tumors. Nevertheless, the flat-shaped detector array has the drawback of a limited view. Here we developed a novel PAM system with a hemispherical-shaped detector array (HDA), which enables us to identify microvasculatures non-invasively and allow the collection of nearly spatially isotropic three-dimensional reconstructed image of blood vessels. This non-invasive vascular imaging system may be able to characterize tumor angiogenesis and analyze the status of microcirculation. The aim of this study was to analyze the imaging findings of tumor-related vasculature in breast cancer patients. Patients and method: A PAM system with HDA has been generated in a cooperation project between Canon Inc., Japan, and Kyoto University. Twenty-two primary breast cancer patients, including 5 patients with non-invasive cancer and 17 patients with invasive cancer, diagnosed between December 2014 and December 2015 underwent the PAM imaging analysis. We also applied the breast deformation algorithm from the breast shape in a MRI image to that in a PA image in order to create a fusion image of the two modalities for the analysis. Features of peri- and intra-tumoral vasculature, and their oxygenation status were evaluated. The study protocol was approved by the institutional review board at Kyoto University Hospital (UMIN000012251). All patients provided informed consent to participate in this study. Results: The abnormal peri-tumoral vasculature was detected in 86% of all non-invasive and invasive disease cases. In invasive cancer cases, most tumor-related blood vessels were centripetally directed toward the tumor, and 93% of centripetal blood vessels appeared to be disrupted or rapidly narrowed at the tumor boundary. The centripetal blood vessel structure was frequently observed in invasive cancer compared with non-invasive cancer (61% vs 35%). PA images before and after preoperative chemotherapy were obtained in one case, where intra-tumoral blood vessels became finer after chemotherapy, reflecting normalization of intra-tumoral microcirculation induced by chemotherapy. Conclusions: A PAM system with HDA has provided a high-resolution vascular images of primary breast cancers. The morphological differences of peri-tumoral vasculature were observed between invasive disease and non-invasive disease. These results suggest the potential of PA imaging as a non-invasive tool to analyze tumor vasculature of human breast cancers and maybe be helpful for breast cancer diagnosis. (Acknowledgements) This work was partially supported by the Innovative Techno-Hub for Integrated Medical Bio-imaging Project of the Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Citation Format: Toi M, Asao Y, Takada M, Kataoka M, Endo T, Kawashima M, Yamaga I, Nakayama Y, Tokiwa M, Fakhrejahani E, Torii M, Kawaguchi-Sakita N, Kanao S, Matsumoto Y, Yagi T, Sakurai T, Togashi K, Shiina T. Development of photoacoustic vascular imaging system for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-10.

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