Abstract P4-03-03: Detection of the tumor vasculature and the hypoxic status of breast lesions using second-generation photoacoustic mammography: An exploratory study
Authors: Takada M , Kawashima M , Kataoka M , Kanao S , Yamaga I , Torii M , Tokiwa M , Fakhrejahani E , Sakurai T , Asao Y , Haga H , Shiina T , Togashi K , Toi M 
Published: May 2016

Abstract
Background: Tumor angiogenesis and hypoxia are associated with breast cancer growth and metastasis. Photoacoustic mammography (PAM) non-invasively visualizes hemoglobin distribution inside the breast by detecting thermoelastic waves from hemoglobin generated by the irradiation of a near-infrared laser pulse. Oxygen saturation (SO2) can be calculated using photoacoustic (PA) signals obtained by two laser pulses of different wavelengths. We further improved the spatial resolution of PAM by approximately 1 mm and enhanced detectability by using a high-sensitivity detector. This new PAM technique can obtain both PAM images and ultrasonography (US) images simultaneously. The aim of this study was to explore the clinical usefulness of this PAM technique.
Patients and methods: Women who had breast lesions were eligible for this study. The participants' lesions were measured using the new PAM technique before they began treatment. The PAM images were evaluated by 5 physicians. First, the lesions were identified using only the PAM images. Second, we used US or contrast-enhanced magnetic resonance images (CE-MRI) to identify the locations of the lesions. Next, we evaluated the photoacoustic (PA) signals based on their locations. Peri-tumoral PA signals were defined as linear signals that congregated in the peri-tumoral area, boundary PA signals were defined as peri-tumoral signals that were disrupted at the lesion's boundaries, and intra-tumoral PA signals were defined as any significant PA signals inside the tumor. SO2 was illustrated using a color scale. The study protocol was approved by the institutional review board at Kyoto University Hospital, Japan (UMIN000007464).
Results: PAM was performed on 48 breast lesions in 45 patients, including 36 invasive carcinoma lesions, 8 ductal carcinoma in situ (DCIS) lesions, and 4 benign lesions. Evaluations of PA signals according to the locations of the lesion, with confirmation from US or CE-MRI, were successfully performed for 38 lesions. Peri-tumoral PA signals were detected in 33 lesions (87%), disrupted boundary PA signals were detected in 30 lesions (79%), and intra-tumoral PA signals were detected in 25 lesions (66%). The detection rates for peri-tumoral, boundary and intra-tumoral PA signals were 94%, 87%, and 65% for invasive carcinoma, and 60%, 40%, and 80% for DCIS, respectively. Intra-tumoral PA signals tended to be weaker than peri-tumoral PA signals in invasive carcinoma lesions, and they often displayed a spotty rather than a linear shape. Intra-tumoral PA signals were observed to have lower SO2 levels than peri-tumoral PA signals in 95% of invasive carcinoma lesions and in 75% of DCIS lesions. Although peri-tumoral and boundary PA signals were also detected in a 38-mm fibroadenoma, the intra-tumoral PA signals displayed a diffuse pattern.
Conclusions: We demonstrated that high spatial resolution and use in combination with US and CE-MRI facilitate the region-specific evaluation of PAM imaging. PAM could become a useful tool for the evaluation of the hypoxic status of tumors by enhancing its sensitivity.
Citation Format: Takada M, Kawashima M, Kataoka M, Kanao S, Yamaga I, Torii M, Tokiwa M, Fakhrejahani E, Sakurai T, Asao Y, Haga H, Shiina T, Togashi K, Toi M. Detection of the tumor vasculature and the hypoxic status of breast lesions using second-generation photoacoustic mammography: An exploratory study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-03.