Macroscopic inelastic scattering imaging using a hyperspectral line-scanning system identifies invasive breast cancer in lumpectomy and mastectomy specimens.

Significance: Of patients with early-stage breast cancer, 60% to 75% undergo breast-conserving surgery. Of those, 20% or more need a second surgery because of an incomplete tumor resection only discovered days after surgery. An intraoperative imaging technology allowing cancer detection on the margins of breast specimens could reduce re-excision procedure rates and improve patient survival. Aim: We aimed to develop an experimental protocol using hyperspectral line-scanning Raman spectroscopy to image fresh breast specimens from cancer patients. Our objective was to determine whether macroscopic specimen images could be produced to distinguish invasive breast cancer from normal tissue structures. Approach: A hyperspectral inelastic scattering imaging instrument was used to interrogate eight specimens from six patients undergoing breast cancer surgery. Machine learning models trained with a different system to distinguish cancer from normal breast structures were used to produce tissue maps with a field-of-view of 1 cm 2 classifying each pixel as either cancer, adipose, or other normal tissues. The predictive model results were compared with spatially correlated histology maps of the specimens. Results: A total of eight specimens from six patients were imaged. Four of the hyperspectral images were associated with specimens containing cancer cells that were correctly identified by the new ex vivo pathology technique. The images associated with the remaining four specimens had no histologically detectable cancer cells, and this was also correctly predicted by the instrument. Conclusions: We showed the potential of hyperspectral Raman imaging as an intraoperative breast cancer margin assessment technique that could help surgeons improve cosmesis and reduce the number of repeat procedures in breast cancer surgery.

A clinical Raman spectroscopy imaging system and safety requirements for in situ intraoperative tissue characterization.

Raman spectroscopy imaging is a technique that can be adapted for intraoperative tissue characterization to be used for surgical guidance. Here we present a macroscopic line scanning Raman imaging system that has been modified to ensure suitability for intraoperative use. The imaging system has a field of view of 1 × 1 cm2 and acquires Raman fingerprint images of 40 × 42 pixels, typically in less than 5 minutes. The system is mounted on a mobile cart, it is equiped with a passive support arm and possesses a removable and sterilizable probe muzzle. The results of a proof of concept study are presented in porcine adipose and muscle tissue. Supervised machine learning models (support vector machines and random forests) were trained and they were tested on a holdout dataset consisting of 7 Raman images (10 080 spectra) acquired in different animal tissues. This led to a detection accuracy >96% and prediction confidence maps providing a quantitative detection assessment for tissue border visualization. Further testing was accomplished on a dataset acquired with the imaging probe's contact muzzle and tailored classification models showed robust classifications capabilities with specificity, sensitivity and accuracy all surpassing 95% with a support vector machine classifier. Finally, laser safety, biosafety and sterilization of the system was assest. The safety assessment showed that the system's laser can be operated safetly according to the American National Standards Institute's standard for maximum permissible exposures for eyes and skin. It was further shown that during tissue interrogation, the temperature-history in cumulative equivalent minutes at 43 °C (CEM43 °C) never exceeded a safe threshold of 5 min.