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Assessment of breast pathologies using nonlinear microscopy.

Yuankai K Tao1, Dejun Shen2, Yuri Sheikine2

  • 1Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139;

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 2014
PubMed
Summary

Nonlinear microscopy (NLM) offers rapid, accurate intraoperative assessment of breast cancer margins on fresh tissue. This innovative technique shows high sensitivity and specificity, potentially reducing reexcision rates in breast-conserving surgery.

Keywords:
breast cancerimagingnonlinear microscopypathology

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Area of Science:

  • Biomedical Optics
  • Surgical Pathology
  • Medical Imaging

Background:

  • Positive or close margins in breast-conserving surgery necessitate reexcision in up to 40% of patients.
  • Accurate, rapid intraoperative margin assessment is crucial for optimizing surgical outcomes.
  • Conventional histopathology requires extensive tissue processing, delaying intraoperative decision-making.

Purpose of the Study:

  • To demonstrate nonlinear microscopy (NLM) for rapid assessment of breast pathologies in fresh surgical specimens.
  • To evaluate the diagnostic accuracy and feasibility of NLM for intraoperative margin evaluation.
  • To develop a visualization method for NLM that aids pathological interpretation.

Main Methods:

  • Nonlinear microscopy (NLM) imaging of 179 fresh breast specimens using acridine orange staining and second harmonic generation.
  • Development of a visualization technique mapping NLM signals to histopathology features.
  • Coregistration of NLM images with standard paraffin-embedded histology for paired assessment.
  • Blinded NLM readings by three pathologists.

Main Results:

  • NLM achieved 95.4% sensitivity and 93.3% specificity for identifying invasive cancer and ductal carcinoma in situ versus benign tissue.
  • High interobserver agreement (κ = 0.88) was observed for NLM readings.
  • NLM imaging was performed rapidly on unfixed specimens without fixation, embedding, or sectioning.

Conclusions:

  • Nonlinear microscopy (NLM) provides high diagnostic accuracy for intraoperative breast cancer margin assessment.
  • NLM is a rapid technique applicable to fresh, unfixed surgical specimens.
  • NLM is a promising tool to potentially reduce reexcision rates in breast cancer surgery.