title: Quantification of tumor fluorescence during intraoperative optical cancer imaging.
abstract: Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 ± 0.6, 2.4 ± 0.3, 2.6 ± 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 ± 0.2 vs. 4.3 ± 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 ± 11.5, 5.1 ± 1.8, 4.1 ± 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 ± 3.4 vs. 2.4 ± 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth.
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Judy
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Keating
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: DeJesus
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Jack X
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Olugbenga T
authors.initials: OT
authors.lastname: Okusanya
authors.affiliation: Emory University, Departments of Biomedical Engineering and Chemistry, Atlanta, 30322, United States of America.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, Philadelphia, 19104, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Holt
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Department of Radiology, Philadelphia, 19104, United States of America.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Arlauckas
authors.affiliation: Purdue University, Department of Chemistry, West Lafayette, 47907, United States of America.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Low
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Department of Radiology, Philadelphia, 19104, United States of America.
authors.forename: E James
authors.initials: EJ
authors.lastname: Delikatny
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Department of Surgery, Philadelphia, 19104, United States of America.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005453:Fluorescence; D006801:Humans; D007432:Intraoperative Period; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000601:surgery*; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000601:surgery*; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014183:Transplantation, Heterologous