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

Wong, Terence T. W. and Zhang, Ruiying and Hai, Pengfei and Zhang, Chi and Pleitez, Miguel A. and Aft, Rebecca L. and Novack, Deborah V. and Wang, Lihong V. (2017) Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy. Science Advances, 3 (5). Art. No. e1602168. ISSN 2375-2548. PMCID PMC5435415. doi:10.1126/sciadv.1602168. https://resolver.caltech.edu/CaltechAUTHORS:20170516-164857493

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/sciadv.1602168DOIArticle
http://advances.sciencemag.org/content/3/5/e1602168PublisherArticle
http://advances.sciencemag.org/cgi/content/full/3/5/e1602168/DC1PublisherSupplementary Materials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435415/PubMed CentralArticle
ORCID:
AuthorORCID
Wong, Terence T. W.0000-0001-6399-758X
Zhang, Ruiying0000-0002-0092-0814
Zhang, Chi0000-0002-1324-2311
Wang, Lihong V.0000-0001-9783-4383
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.
Funders:
Funding AgencyGrant Number
NIHDP1 EB016986
NIHR01 CA186567
Siteman Cancer CenterUNSPECIFIED
Subject Keywords:Label-freemulti-layer histology; unprocessed tissue; human breast cancer; photoacoustic imaging; margin analysis
Issue or Number:5
PubMed Central ID:PMC5435415
DOI:10.1126/sciadv.1602168
Record Number:CaltechAUTHORS:20170516-164857493
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170516-164857493
Official Citation:T. T. W. Wong, R. Zhang, P. Hai, C. Zhang, M. A. Pleitez, R. L. Aft, D. V. Novack, L. V. Wang, Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy. Sci. Adv. 3, e1602168 (2017)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:77511
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:17 May 2017 18:48
Last Modified:15 Nov 2021 17:31

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