Multiparametric Spectroscopic Photoacoustic Imaging of Breast Cancer Development in a Transgenic Mouse Model

Objective: To evaluate the potential of multiparametric spectroscopic photoacoustic imaging using oxygen saturation, total hemoglobin, and lipid content to differentiate among four different breast histologies (normal, hyperplasia, ductal carcinoma in situ (DCIS), and invasive breast carcinoma) in a transgenic mouse model of breast cancer development. Materials and Methods: Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mammary glands (n=251) of a transgenic mouse model of breast cancer development (FVB/N-Tg(MMTV-PyMT)634Mul) were imaged using B-mode ultrasound and spectroscopic photoacoustic imaging, analyzed for oxygen saturation, total hemoglobin, and lipid content, and processed for histological analysis. Statistical analysis was performed using one-way ANOVA, two-sample t-tests, logistic regression, and ROC analysis. Results: Eighty-two normal, 12 hyperplastic, 96 DCIS, and 61 invasive breast carcinoma mammary glands were analyzed. Based on spectroscopic photoacoustic imaging, the oxygen saturation of hyperplasia (50.6%), DCIS (43.0%), and invasive carcinoma (46.2%) significantly increased compared to normal glands (35.5%, P <0.0001), while both total hemoglobin (P<0.01), and lipid content (P<0.0008) significantly decreased with advancing histology. In differentiating normal and hyperplasia from DCIS and invasive breast carcinoma, multiparametric imaging of oxygen saturation, lipid content, and raw photoacoustic signal at 750 nm provided an AUC value of 0.770. Conclusion: Multiparametric spectroscopic photoacoustic imaging is feasible and allows detection of differences in concentration of tissue chromophores among different histologies in a transgenic mouse model of breast cancer development.