Abstract

This study evaluates the potential for fluorescence lifetime imaging (FLIm) to enhance intraoperative decisionmaking during robotic-assisted surgery of oropharyngeal cancer. Using a custom built FLIm instrument integrated with the da Vinci robotic surgical platform, we first demonstrate that cancer in epithelial tissue diagnosed by histopathology can be differentiated from surrounding healthy epithelial tissue imaged in vivo prior to cancer resection and ex vivo on the excised specimen. Second, we study the fluorescence properties of tissue imaged in vivo at surgical resection margins (tumor bed). Fluorescence lifetimes and spectral intensity ratios were calculated for three spectral channels, producing a set of six FLIm parameters. Current results from 10 patients undergoing TORS procedures demonstrate that healthy epithelium can be resolved from cancer (P < .001) for at least one FLIm parameter. We also showed that a multiparameter linear discriminant analysis approach provides superior discrimination to individual FLIm parameters for tissue imaged both in vivo and ex vivo. Overall, this study highlights the potential for FLIm to be developed into a diagnostic tool for clinical cancer applications of the oropharynx. This technique could help to circumvent the issues posed by the lack of tactile feedback associated with robotic surgical platforms to better enable cancer delineation.

Highlights

  • In the United States, oral and oropharyngeal cancer together represent 3.0% of all new cancer cases, are associated with a 65.3% survivability after 5 years from initial onset, and are expected to afflict 53 000 individuals in 2019 [1]

  • fluorescence lifetime imaging (FLIm) measurements acquired from patients (n = 10) and subsequently analyzed generated a total of 42 777 FLIm data points coregistered with histopathology. 13 765 of these data points were associated to cancer and the remaining 29 012 to healthy tissue

  • Detailed results from two case studies (“A” and “B”), a summary of the statistical significance and discriminative metrics for the entire 10-patient cohort, and a comparison of normal tissue FLIm signatures between the three imaging contexts are presented. These case studies were selected for the following reasons: (a) they highlight different levels of single parameter contrast and show how limited contrast can be overcome through a multiparameter LDA approach when necessary and (b) distinct tissue conditions are observed in the histopathology for each case

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Summary

Introduction

In the United States, oral and oropharyngeal cancer together represent 3.0% of all new cancer cases, are associated with a 65.3% survivability after 5 years from initial onset, and are expected to afflict 53 000 individuals in 2019 [1]. Over the last two decades, roboticassisted surgery has become widely utilized for the surgical resection of oropharyngeal cancers. Transoral robotic surgery (TORS) confers many advantages compared to conventional endoscopy procedures; this includes deeper access to anatomical sites which enables precise operation in tight spaces without a large open incision, improved patient functional outcomes, and improved dissection ability of lesions and neoplastic growths [3]. Adequate intraoperative delineation of cancer is the key factor for long-term survival of patients diagnosed with oral and oropharyngeal cancer [4]. This requires rapid evaluation of the extent of molecular changes (neoplastic area) of the epithelial surface (mucosa). During conventional surgical resection procedures, surgeons typically leverage all three methods, as well as other screening tests, to provide informed intraoperative diagnosis [5]

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