Abstract P3-01-02: Clinical, anatomical and histological characteristics of breast lesions visualized by photoacoustic mammography; first clinical study in CK project
Authors: Fakhrejahani Elham , Torii Masae , Asao Yasufumi , Yamaga Iku , Kitai Toshiyuki , Kataoka Masako , Kanao Shotaro , Takada Masahiro , Shiina Tsuyoshi , Toi Masakazu 
Published: May 2015

Abstract
Background: Photoacoustic mammography (PAM) is an optical imaging technique potentially capable of imaging breast vasculature as well as measuring hemoglobin oxygen saturation(SO2) in focal breast lesions. We presented the initial observation on first 20 cases using the first generation PAM (PAM-01) prototype made by Canon Inc.(Tokyo, Japan) (spatial resolution:2mm) in SABCS 2013. Here we report the clinico-pathological characteristics of all cases recruited in the first clinical study in CK project (Kyoto University/Canon joint research project) between Aug 2010 and March 2012.
Methods: 57 patients were recruited in IRB approved study at Kyoto University Hospital, Japan. Forty-two breast harboring lesions and when possible contralateral breasts were evaluated by PAM-01. Axial maximum intensity projection (MIP)s were obtained and signals from consecutive MIPs confirmed to be associated with the tumor location in MRI by an expert breast radiologist were considered to be the region of interest (ROI).The same depth was used for ROI in the normal breast as control. Histological sections from the widest area of the lesions were evaluated post-excisional by immunohistochemistry using anti-CD31 as endothelial marker and anti-carbonic anhydrase IX (CA IX) as hypoxia marker. Histological slides were scanned and divided into 1680 squares (0.84x0.84 mm2)(Hamamatsu Inc. Japan) for image analysis. Total vascular perimeter (TVP)-in mm- was calculated for all the histological section by using Image Pro-Plus 7.0 software (Media Cybernetics, USA). Tumor area was measured in mm2. TVP index was calculated as TVP/area.
Results: Photoacoustic signal was detected in 30 lesions out of 42 at the depth of 26.8 ± 12.8 mm from which 80% were located superior to nipple. CA IX positive cases in comparison with CA IX negative cases significantly showed higher TVP index (p-value =0.028 Mann-Whitney Test ) suggesting more angiogenic profile of hypoxic tumors. However, lesions without any detectable signal were reported to have only a bigger mass size histologically (26.6 vs. 14.8 mm, p-value 0.28, Mann-Whitney Test) regardless of their TVP index or CA IX expression level. Moreover,SO2 was calculated 70.9% for signals located inside tumors and 85.5% for signals associated with subcutaneous vessels in the same breast (p-value &lt;0.0001 Wilcoxon Test) compatible with the SO2 data from normal counterpart at tumor depth in the other breast (81.9%) (p-value 0.0001 Wilcoxon Test). Tumors bigger than 2 cm also tended to have lower SO2 (65.6%) compared with tumors smaller than 2 cm (70.1%) in accordance with higher TVP index in bigger tumors (p-value &lt;0.001 Student T-test).
Conclusion: This is the largest clinical study of PAM till today and the correlation between histological profile of hypoxia and tumor microvasculature with PAM signal visibility as well as tissue SO2 seems promising. However, the improvement of techniques and resolution is necessary to develop a more clinically applicable non-invasive functional breast imaging modality for analyzing breast tumor vasculature and hypoxia. Some of these improvements have taken place for the second generation PAM (PAM-02) which is now under a clinical evaluation study.
Citation Format: Elham Fakhrejahani, Masae Torii, Yasufumi Asao, Iku Yamaga, Toshiyuki Kitai, Masako Kataoka, Shotaro Kanao, Masahiro Takada, Tsuyoshi Shiina, Masakazu Toi. Clinical, anatomical and histological characteristics of breast lesions visualized by photoacoustic mammography; first clinical study in CK project [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 P3-01-02.