Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy

Daniel A. Orringer, Balaji Pandian, Yashar S. Niknafs, Todd C. Hollon, Julianne Boyle, Spencer Lewis, Mia Garrard, Shawn L. Hervey-Jumper, Hugh J.L. Garton, Cormac O. Maher, Jason A. Heth, Oren Sagher, D. Andrew Wilkinson, Matija Snuderl, Sriram Venneti, Shakti H. Ramkissoon, Kathryn A. McFadden, Amanda Fisher-Hubbard, Andrew P. Lieberman, Timothy D. JohnsonX. Sunney Xie, Jay K. Trautman, Christian W. Freudiger, Sandra Camelo-Piragua

Research output: Contribution to journalArticlepeer-review

342 Scopus citations


Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients. We also introduce an image-processing method - stimulated Raman histology (SRH) - that leverages SRS images to create virtual haematoxylin-and-eosin-stained slides, revealing essential diagnostic features. In a simulation of intraoperative pathologic consultation in 30 patients, we found a remarkable concordance of SRH and conventional histology for predicting diagnosis (Cohen's kappa, κ > 0.89), with accuracy exceeding 92%. We also built and validated a multilayer perceptron based on quantified SRH image attributes that predicts brain-tumour subtype with 90% accuracy. Our findings provide insight into how SRH can now be used to improve the surgical care of brain-tumour patients.

Original languageEnglish (US)
Article number0027
JournalNature Biomedical Engineering
Issue number2
StatePublished - Feb 10 2017

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications


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