title: Trimodal color-fluorescence-polarization endoscopy aided by a tumor selective molecular probe accurately detects flat lesions in colitis-associated cancer.
abstract: Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real-time detection of these lesions. Using azoxymethane-dextran sodium sulfate (AOM-DSS) treated mice, which recapitulates human CAC and dysplasia, we show that an octapeptide labeled with a near-infrared (NIR) fluorescent dye selectively identified all precancerous and cancerous lesions. A new thermoresponsive sol-gel formulation allowed topical application of the molecular probe during endoscopy. This method yielded high contrast-to-noise ratios (CNR) between adenomatous tumors (20.6 ± 1.65) and flat lesions (12.1 ± 1.03) and surrounding uninvolved colon tissue versus CNR of inflamed tissues (1.62±0.42) Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy shows a high depolarization contrast in both adenomatous tumors and flat lesions in CAC, reflecting compromised structural integrity of these tissues. Together, the real-time polarization imaging provides real-time validation of suspicious colon tissue highlighted by molecular fluorescence endoscopy.
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United StatesbWashington University in St. Louis, Department of Biomedical Engineering, 1 Brookings Drive, St. Louis, Missouri 63110.
authors.forename: Tauseef
authors.initials: T
authors.lastname: Charanya
authors.affiliation: Washington University in St. Louis, Department of Computer Science and Engineering, 1 Brookings Drive, St. Louis, Missouri 63110, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: York
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Bloch
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United States.
authors.forename: Gail
authors.initials: G
authors.lastname: Sudlow
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United States.
authors.forename: Kexian
authors.initials: K
authors.lastname: Liang
authors.affiliation: Washington University in St. Louis, Department of Computer Science and Engineering, 1 Brookings Drive, St. Louis, Missouri 63110, United States.
authors.forename: Missael
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United States.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Akers
authors.affiliation: Washington University in St. Louis, Department of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, United States.
authors.forename: Deborah
authors.initials: D
authors.lastname: Rubin
authors.affiliation: Washington University in St. Louis, Department of Computer Science and Engineering, 1 Brookings Drive, St. Louis, Missouri 63110, United States.
authors.forename: Viktor
authors.initials: V
authors.lastname: Gruev
authors.affiliation: Washington University in St. Louis, Department of Radiology, 4525 Scott Avenue, East Building, St. Louis, Missouri 63110, United StatesbWashington University in St. Louis, Department of Biomedical Engineering, 1 Brookings Drive, St. Louis, Missouri 63110.
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D000818:Animals; D003092:Colitis / Q000473:pathology*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology*; D004724:Endoscopy / Q000379:methods*; D004867:Equipment Design; D005454:Fluorescence Polarization / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D011230:Precancerous Conditions; D019265:Spectroscopy, Near-Infrared / Q000379:methods*