title: Quantitative, spectrally-resolved intraoperative fluorescence imaging.
abstract: Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the first time. Moreover, we present images from human surgery which detect residual tumor not evident with state-of-the-art vFI. The wide-field qFI technique has broad implications for intraoperative surgical guidance because it provides near real-time quantitative assessment of multiple fluorescent biomarkers across the operative field.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. Pablo.A.Valdes@Dartmouth.edu
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Valdés
authors.forename: Frederic
authors.initials: F
authors.lastname: Leblond
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Jacobs
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000601:surgery*; D005453:Fluorescence; D005456:Fluorescent Dyes; D005910:Glioma / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D007432:Intraoperative Period; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D019047:Phantoms, Imaging; D011524:Protoporphyrins; D051381:Rats
chemical_list: D005456:Fluorescent Dyes; D011524:Protoporphyrins; C028025:protoporphyrin IX