FULL ARTICLE Photoacoustic imaging of breast microcalcifications: A validation study with 3-dimensional ex vivo data and spectrophotometric measurement Jeeun Kang 1 , Eun-kyung Kim 2 , Ga Ram Kim 2 , Changhan Yoon 1 , Tai-kyong Song 1 , and Jin Ho Chang * ; 1; 3; 4 1 Department of Electronic Engineering, Sogang University, Seoul 121-742, Korea 2 Department of Radiology, Research Institute of Radiological Science, Yonsei College of Medicine, Seoul 121-749, Korea 3 Sogang Institute of Advanced Technology, Sogang University, Seoul 121-742, Korea 4 Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul 121-742, Korea Received 23 June 2013, revised 18 August 2013, accepted 19 August 2013 Published online 3 September 2013 Key words: Photoacoustic imaging, breast cancer screening, microcalcifications, mammography, ultrasonography, hydroxyapatite, calcium oxalate 1. Introduction Breast microcalcifications (i.e., < 1 mm) have drawn many attentions as an early indicator of breast can- cer. The mechanism of mammary mineralization and its influence on cancerous cell proliferation have not been fully understood, but it is known that the ab- normal chemical circumstance of breast tissue, e.g., an overexpression of alkaline phosphatase (ALP) can accelerate the formation of breast microcalcifica- tions [1, 2]. Also, several studies have demonstrated that the microcalcifications is highly related to the development of breast tumor [1, 3]. Therefore, if the microcalcifications are found in abnormal breast le- sions through breast cancer screening, needle biopsy followed by histological examination is generally # 2015 by WILEY-VCH Verlag GmbH& Co. KGaA, Weinheim Journal of BIOPHOTONICS This paper investigates whether photoacoustic imaging (PAI) can provide the visualization of microcalcifications in breast tissue. For this, the geometrical correlation be- tween the 3-D PA images of breast microcalcifications within ex vivo specimens and the corresponding mammo- grams was ascertained. Also, the optical absorbance of the calcification compositions (i.e., hydroxyapatite and calcium oxalate) was measured and compared with the PA responses of the microcalcifications. The experimen- tal results demonstrated that the PA images discrimi- nated between the microcalcifications and the surround- ing tissue, and their locations in PA images reasonably meshed with those of the microcalcifications appeared in the mammograms. Also, the change in PA signal ampli- tude along the laser wavelength agreed with the absorb- ance of hydroxyapatite associated with the relatively high potential of malignant cancers, but not calcium oxa- late with only benign cases. Spectroscopic photoacoustic images and corresponding mammograms in (a, b) lateral and (c, d) axial directions, respectively. The spectroscopic PA images were overlaid on the corresponding grayscale US images. * Corresponding author: e-mail: jhchang@sogang.ac.kr J. Biophotonics 8, No. 1–2, 71–80 (2015) / DOI 10.1002/jbio.201300100