Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy

Tissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However,...

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Main Authors: Kong, Kenny, Rowlands, Christopher J., Varma, Sandeep, Perkins, William, Leach, Iain H., Koloydenko, Alexey A., Williams, Hywei C., Notingher, Ioan
Format: Article
Published: National Academy of Sciences 2013
Online Access:https://eprints.nottingham.ac.uk/33050/
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author Kong, Kenny
Rowlands, Christopher J.
Varma, Sandeep
Perkins, William
Leach, Iain H.
Koloydenko, Alexey A.
Williams, Hywei C.
Notingher, Ioan
author_facet Kong, Kenny
Rowlands, Christopher J.
Varma, Sandeep
Perkins, William
Leach, Iain H.
Koloydenko, Alexey A.
Williams, Hywei C.
Notingher, Ioan
author_sort Kong, Kenny
building Nottingham Research Data Repository
collection Online Access
description Tissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However, its use during tissue-conserving surgery is limited by time-consuming tissue preparation steps (1–2 h) and the diagnostic variability inherent in subjective image interpretation. Here, we demonstrate an integrated optical technique based on tissue autofluorescence imaging (high sensitivity and high speed but low specificity) and Raman scattering (high sensitivity and high specificity but low speed) that can overcome these limitations. Automated segmentation of autofluorescence images was used to select and prioritize the sampling points for Raman spectroscopy, which then was used to establish the diagnosis based on a spectral classification model (100% sensitivity, 92% specificity per spectrum). This automated sampling strategy allowed objective diagnosis of basal cell carcinoma in skin tissue samples excised during Mohs micrographic surgery faster than frozen section histopathology, and one or two orders of magnitude faster than previous techniques based on infrared or Raman microscopy. We also show that this technique can diagnose the presence or absence of tumors in unsectioned tissue layers, thus eliminating the need for tissue sectioning. This study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed.
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spelling nottingham-330502020-04-29T14:59:58Z https://eprints.nottingham.ac.uk/33050/ Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy Kong, Kenny Rowlands, Christopher J. Varma, Sandeep Perkins, William Leach, Iain H. Koloydenko, Alexey A. Williams, Hywei C. Notingher, Ioan Tissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However, its use during tissue-conserving surgery is limited by time-consuming tissue preparation steps (1–2 h) and the diagnostic variability inherent in subjective image interpretation. Here, we demonstrate an integrated optical technique based on tissue autofluorescence imaging (high sensitivity and high speed but low specificity) and Raman scattering (high sensitivity and high specificity but low speed) that can overcome these limitations. Automated segmentation of autofluorescence images was used to select and prioritize the sampling points for Raman spectroscopy, which then was used to establish the diagnosis based on a spectral classification model (100% sensitivity, 92% specificity per spectrum). This automated sampling strategy allowed objective diagnosis of basal cell carcinoma in skin tissue samples excised during Mohs micrographic surgery faster than frozen section histopathology, and one or two orders of magnitude faster than previous techniques based on infrared or Raman microscopy. We also show that this technique can diagnose the presence or absence of tumors in unsectioned tissue layers, thus eliminating the need for tissue sectioning. This study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed. National Academy of Sciences 2013-09-17 Article PeerReviewed Kong, Kenny, Rowlands, Christopher J., Varma, Sandeep, Perkins, William, Leach, Iain H., Koloydenko, Alexey A., Williams, Hywei C. and Notingher, Ioan (2013) Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy. Proceedings of the National Academy of Sciences, 110 (38). pp. 15189-15194. ISSN 0027-8424 http://dx.doi.org/10.1073/pnas.1311289110 doi:10.1073/pnas.1311289110 doi:10.1073/pnas.1311289110
spellingShingle Kong, Kenny
Rowlands, Christopher J.
Varma, Sandeep
Perkins, William
Leach, Iain H.
Koloydenko, Alexey A.
Williams, Hywei C.
Notingher, Ioan
Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title_full Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title_fullStr Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title_full_unstemmed Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title_short Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy
title_sort diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and raman scattering microscopy
url https://eprints.nottingham.ac.uk/33050/
https://eprints.nottingham.ac.uk/33050/
https://eprints.nottingham.ac.uk/33050/