Abstract

Abstract Background: Functional imaging of tumor vasculature and oxygenation status is essential for monitoring the therapeutic response to the manipulation of abnormal vasculature. Moreover, it could be also applicable for the detection and risk assessment of breast lesion with borderline malignancy since hypoxia and angiogenesis is known to be associated with the malignant potential of precursor lesion of solid tumor. Photoacoustic mammography (PAM) is a novel optical imaging technology that can visualize the hemoglobin distribution and its oxygen saturation (SO2) noninvasively. We have previously reported a promising clinical result of a prototype model of PAM (Canon Inc., Tokyo, Japan) in breast cancer patients. However, the improvement of spatial resolution and the identification of signal origin are still big challenges when considering its application for clinical settings. Materials and methods: We developed the second-generation model of PAM (PAM-02). This instrument has achieved the improved spatial resolution (1.3mm) and enhanced detectability by carrying a high-sensitive detector. Moreover, it is equipped with B-mode ultrasound, which enables us to identify the tumor location in PAM images more precisely. The distribution of hemoglobin within breast tissue carrying solid tumor was evaluated by using PAM-02 under the approval of the ethics committee in Kyoto University Hospital, Japan. Contralateral breast without tumor was also evaluated as a control if possible. Calculated SO2 from photoacoustic (PA) signals were illustrated by using color scale. Results: Seventeen breast lesions from 15 patients were analyzed including 4 ductal carcinoma in situ (DCIS), 12 invasive ductal carcinoma (IDC) and one usual ductal hyperplasia. Tumor locations were successfully identified in 14 out of 17 lesions (82.3%) by B-mode ultrasound imaging. The location of 3 lesions undetectable by B-mode ultrasound imaging could be identified by comparing with corresponding MRI images. B-mode ultrasound imaging made it easy to distinguish intra-tumoral PA signals from peri-tumoral PA signals. Intra-tumoral PA signals were detectable in 68.7% of malignant lesions (11 out of 16 lesions). Peri-tumoral PA signals, which were suggested to be from feeding vessels, were detectable in 81.3% of malignant lesion (13 out of 16 lesions). In the case of benign UDH, PA signals were not detected in either intra- or peri-tumoral region. Intra-tumoral SO2 was estimated to be lower than peri-tumoral SO2 in malignant lesion. While peri-tumoral PA signals were often described as continuous vasculature, intra-tumoral PA signals often showed the spotty patterns. In addition, PA signal density was relatively higher in DCIS compared with IDC. These findings was supposed to reflect the decreased hemoglobin perfusion within solid structure of breast cancer. The minimum detectable lesion was DCIS with a diameter of 8mm. Conclusion: Improved spatial resolution and combination with B-mode ultrasound imaging facilitate the region-specific evaluation of PAM imaging. PAM-02 was supposed to be feasible for evaluating the hypoxic status within small breast tumor and its microenvironment. Citation Format: Masahiro Kawashima, Iku Yamaga, Masae Torii, Mariko Tokiwa, Fakhrejahani Elham, Masako Kataoka, Shotaro Kanao, Masahiro Takada, Yasufumi Asao, Tsuyoshi Shiina, Masakazu Toi. Evaluation of second-generation photoacoustic mammography in detecting the breast cancer vasculature and hypoxic status; a preliminary study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-01.

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