Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

"Disclosures: Edoardo Charbon holds the position of Chief Scientific Officer of Fastree3D, a company making LiDAR systems for the automotive market, and Claudio Bruschini and Edoardo Charbon are co-founders of Pi Imaging Technology. Neither company has been involved with the work of this paper. No other authors have competing interests as related to the content of this work."

"This work was funded by the National Institutes of Health [(Grant Nos. P01 CA084203 (B.W.P.) and R01 EB032337 (B.W.P.)] and Dartmouth Cancer Center development funding (P.B.)."

"To test our system in a clinical setting, two representative slices from two freshly resected head and neck tumors were imaged using the same settings as for the previous experiments (Sec. ). The patients involved were enrolled in a clinical study to examine the value of ABY-029 (an antiepithelial growth factor receptor Affibody molecule labeled with IRDye 800CW) for demarking tumor tissue (ClinicalTrials.gov Identifier: NCT03282461). All procedures followed an approved Institutional Review Board protocol at Dartmouth Hitchcock Medical Center (DHMC), Lebanon, New Hampshire, United States. Each patient in the study was administered 180 nanomoles of solubilized ABY-029 via intravenous injection 2 to 4 h prior to surgery. Surgery proceeded according to standard-of-care; no fluorescence imaging was performed intraoperatively, and fluorescence imaging results did not in any way impact clinical decision making. Resected tissues were breadloafed into sections in the gross pathology laboratory at DHMC according to standard-of-care. The final step for the ABY-029 clinical study involved fluorescence imaging of representative tissue sections using a closed-field, commercial fluorescence scanning imager (Odyssey CLx, Li-COR Biosciences, Lincoln, Nebraska, United States) for complete measurement of signal on the exposed surfaces. The large-format SPAD camera imaging for the present study was conducted in the gross pathology laboratory, prior to imaging in the closed-field scanner."