Fluorescence lifetime imaging for intraoperative cancer delineation in transoral robotic surgery

Abstract

This study evaluates the potential for fluorescence lifetime imaging (FLIm) to enhance intraoperative decisionmaking during roboticassisted 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.

Real-time diagnosis and visualization of tumor margins in excised breast specimens using fluorescence lifetime imaging and machine learning

“…While this study focused on excised specimens, the long-term goal is to establish FLIm as an intraoperative tool scanning the surgical bed with a fiber optic. Recent studies from our group demonstrated the applicability of FLIm for in vivo applications [17,22,41]. The transition from ex vivo to in vivo settings will involve a few adaptations of the procedure.…”

“…Recent studies have demonstrated that FLIm images can be acquired either during surgery [17][18][19] or on excised specimens [10] to characterize biochemical features and associated pathologies. In particular, FLIm has been demonstrated to identify breast tumor regions [10,20], glioma tumors [21], oropharyngeal cancer [22] and atherosclerotic lesions [18]. In a recent study, the ability to identify breast tumors was demonstrated for small regions correlated visually with histology slides [10].…”

Lasers and Robots: Recent Developments in Transoral Laser and Transoral Robotic Surgery

“…An additional technique for real-time identification of cancerous growth during transoral surgery makes use of fluorescence lifetime imaging (FLIM) observed through and intraoperative fluorescence spectroscopy. 23,24 This type of enhanced intraoperative visualization takes advantage of the autofluorescence capabilities of the tissues to distinguish malignant and premalignant tissues from surrounding tissues. Using a modified robotic arm containing a multimode fiberoptic, an excitation laser is delivered to the tissue region to induce autofluorescence of porphyrins, Nicotinamide adenine dinucleotide phosphate (NAD(P)H), and flavin adenine dinucleotide (FAD).…”

“…23,24 With this method, cancerous tissues can be identified without the application of exogenous probes and the re-sectioned sites can be intraoperatively examined for remaining tumors post-extraction. [23][24][25] Although FLIM can provide an effective means of detecting cancerous tissues based on changes in the molecular composition of cells, the study has found that several factors can affect this type of image guidance. Among the factors that could affect FLIM under TORS are tissue diversity, thickness of the epithelium, cancer cell type, removal method (leaser or electrocautery), and presence of bleeding.…”

“…Previously discussed studies on deformable CT registration and FLIM were carried out with augmented reality (AR) in mind. 20,21,23,24,30 These imaging techniques were designed to overlay visual information on the endoscopic video feed. The deformable CT imaging is integrated into TORS as a means to visualize the target tissue within the three-dimensionally mapped out the surgical site.…”