TY - JOUR
T1 - Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements
AU - Homulle, Harald
AU - Powolny, F
AU - Stegehuis, PL
AU - Dijkstra, J
AU - Li, DU
AU - Homicsko, K
AU - Rimoldi, D.
AU - Muehlethaler, K.
AU - Prior, JO
AU - Sinisi, R
AU - Dubikovskaya, E
AU - Charbon, Edoardo
AU - Bruschini, C
PY - 2016/4/11
Y1 - 2016/4/11
N2 - 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 αvβ3 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
AB - 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 αvβ3 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
KW - Photon counting
KW - Imaging systems
KW - Fluorescence microscopy
KW - Lifetime-based sensing
KW - Medical and biological imaging
KW - Photodetectors
KW - OA-Fund TU Delft
UR - http://resolver.tudelft.nl/uuid:321c0775-8a97-4b69-aaf5-8798f1fc518a
U2 - 10.1364/BOE.7.001797
DO - 10.1364/BOE.7.001797
M3 - Article
SN - 2156-7085
VL - 7
SP - 1797
EP - 1814
JO - Biomedical Optics Express
JF - Biomedical Optics Express
IS - 5
ER -
