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Published May 17, 2017 | Supplemental Material + Published
Journal Article Open

Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy


The goal of breast-conserving surgery is to completely remove all of the cancer. Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen, which results in 20 to 60% of patients undergoing second surgeries to achieve clear margins. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment. We demonstrate that by taking advantage of the intrinsic optical contrast of breast tissue, photoacoustic microscopy (PAM) can achieve multilayered histology-like imaging of the tissue surface. The high correlation of the PAM images to the conventional histologic images allows rapid computations of diagnostic features such as nuclear size and packing density, potentially identifying small clusters of cancer cells. Because PAM does not require tissue processing or staining, it can be performed promptly and intraoperatively, enabling immediate directed re-excision and reducing the number of second surgeries.

Additional Information

© 2017 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. Submitted 8 September 2016; Accepted 23 March 2017; Published 17 May 2017. We thank J. Ballard for the close reading of the manuscript and J. Yao for the meaningful discussion. This work was supported by NIH grants DP1 EB016986 (NIH Director's Pioneer Award) and R01 CA186567 (NIH Director's Transformative Research Award) and by the Siteman Cancer Center (2014 Research Development Award in Breast Cancer). Author contributions: T.T.W.W., R.Z., C.Z., R.L.A., D.V.N., and L.V.W. conceived and designed the study. T.T.W.W., R.Z., C.Z., and M.A.P. constructed the imaging system. R.L.A. obtained informed consent and collected the breast cancer specimens. D.V.N. prepared the histology equivalent images. T.T.W.W. and C.Z. performed the experiments. T.T.W.W., R.Z., and D.V.N. analyzed the data. T.T.W.W. and P.H. processed the data. T.T.W.W., R.L.A., D.V.N., and L.V.W. wrote the manuscript. R.L.A., D.V.N., and L.V.W. supervised the whole study. Competing interests: L.V.W. has a financial interest in MicroPhotoAcoustics Inc., which, however, did not support this work. L.V.W. serves as chair of the Scientific Advisory Board of MicroPhotoAcoustics Inc. Washington University has a patent application related to this work, filed 7 December 2012 (PCT/US2012/068403). The rest of the authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

Attached Files

Published - e1602168.full.pdf

Supplemental Material - 1602168_MovieS1.mp4

Supplemental Material - 1602168_MovieS2.mp4

Supplemental Material - 1602168_SM.pdf


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