Assessment of breast pathologies using nonlinear microscopy
Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast...
| Main Authors: | , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/96899 https://orcid.org/0000-0003-4811-3429 https://orcid.org/0000-0002-0828-4357 |
| _version_ | 1826201940162248704 |
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| author | Shen, D. Sheikine, Y. Wang, H. H. Schmolze, D. B. Johnson, N. B. Brooker, J. S. Cable, Alex E. Connolly, J. L. Tao, Yuankai K. Ahsen, Osman Oguz Fujimoto, James G. |
| author2 | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science |
| author_facet | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Shen, D. Sheikine, Y. Wang, H. H. Schmolze, D. B. Johnson, N. B. Brooker, J. S. Cable, Alex E. Connolly, J. L. Tao, Yuankai K. Ahsen, Osman Oguz Fujimoto, James G. |
| author_sort | Shen, D. |
| collection | MIT |
| description | Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment. |
| first_indexed | 2024-09-23T11:59:43Z |
| format | Article |
| id | mit-1721.1/96899 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:59:43Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/968992022-09-27T23:18:08Z Assessment of breast pathologies using nonlinear microscopy Shen, D. Sheikine, Y. Wang, H. H. Schmolze, D. B. Johnson, N. B. Brooker, J. S. Cable, Alex E. Connolly, J. L. Tao, Yuankai K. Ahsen, Osman Oguz Fujimoto, James G. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Tao, Yuankai K. Ahsen, Osman Oguz Fujimoto, James G. Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment. National Institutes of Health (U.S.) (Grant R01-CA178636-01) National Institutes of Health (U.S.) (Grant R01-CA75289-16) United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551) United States. Air Force Office of Scientific Research (Grant FA9550-12-1-0499) National Institutes of Health (U.S.) (National Research Service Award Postdoctoral Fellowship F32-CA165484) 2015-05-04T16:10:47Z 2015-05-04T16:10:47Z 2014-10 2014-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/96899 Tao, Y. K., D. Shen, Y. Sheikine, O. O. Ahsen, H. H. Wang, D. B. Schmolze, N. B. Johnson, et al. “Assessment of Breast Pathologies Using Nonlinear Microscopy.” Proceedings of the National Academy of Sciences 111, no. 43 (October 13, 2014): 15304–15309. https://orcid.org/0000-0003-4811-3429 https://orcid.org/0000-0002-0828-4357 en_US http://dx.doi.org/10.1073/pnas.1416955111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Shen, D. Sheikine, Y. Wang, H. H. Schmolze, D. B. Johnson, N. B. Brooker, J. S. Cable, Alex E. Connolly, J. L. Tao, Yuankai K. Ahsen, Osman Oguz Fujimoto, James G. Assessment of breast pathologies using nonlinear microscopy |
| title | Assessment of breast pathologies using nonlinear microscopy |
| title_full | Assessment of breast pathologies using nonlinear microscopy |
| title_fullStr | Assessment of breast pathologies using nonlinear microscopy |
| title_full_unstemmed | Assessment of breast pathologies using nonlinear microscopy |
| title_short | Assessment of breast pathologies using nonlinear microscopy |
| title_sort | assessment of breast pathologies using nonlinear microscopy |
| url | http://hdl.handle.net/1721.1/96899 https://orcid.org/0000-0003-4811-3429 https://orcid.org/0000-0002-0828-4357 |
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