title: Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements.
abstract: In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores' lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the αvβ 3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG-E[c(RGD f K)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG-c(RGD f K). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions.
authors.affiliation: AQUA group, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Ludwig Center of the University of Lausanne, Lausanne, Switzerland.
authors.forename: H A R
authors.initials: HA
authors.lastname: Homulle
authors.affiliation: AQUA group, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Powolny
authors.affiliation: Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: P L
authors.initials: PL
authors.lastname: Stegehuis
authors.affiliation: Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Dijkstra
authors.affiliation: LCBIM group, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: D-U
authors.initials: DU
authors.lastname: Li
authors.affiliation: University of Strathclyde, Centre for Biophotonics, Glasgow, UK.
authors.forename: K
authors.initials: K
authors.lastname: Homicsko
authors.affiliation: Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Rimoldi
authors.affiliation: Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Muehlethaler
authors.affiliation: Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: J O
authors.initials: JO
authors.lastname: Prior
authors.affiliation: Delft University of Technology (TU Delft), Delft, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Sinisi
authors.affiliation: Delft University of Technology (TU Delft), Delft, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Dubikovskaya
authors.affiliation: AQUA group, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Ludwig Center of the University of Lausanne, Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Charbon
authors.affiliation: AQUA group, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Bruschini
keywords: (030.5260) Photon counting; (170.2520) Fluorescence microscopy; (170.3650) Lifetime-based sensing; (170.3880) Medical and biological imaging; (230.5160) Photodetectors