@inproceedings{01H40WVFZ7TSMTR4NB8ZB2RM3X,
  abstract     = {{Near-infrared (NIR) fluorescence has emerged as a safe tool in various stages of (pre-)clinical tumor imaging. Conventional systems rely on fluorescence detection by spectral filtering. However, fluorescence also exhibits a specific time-domain behavior, the fluorescence lifetime (FLT) which can be used as an additional filter. Recently, the first clinical ex vivo results [1,2] revealed that FLT can improve tumor imaging. Presented here are the first macroscale in vivo results for a novel imaging system that aims to add these FLT capabilities to fluorescence-guided surgery.

The FLT imaging system is built around the tauCAM, housing a custom fast-gated CMOS image sensor [3] and 775 nm LASER excitation with detection around 835 nm. It offers a large working area and focus between 30 and 7cm with sufficient field-of-view for imaging a full mouse. FLT images are taken with configurable time-domain resolution and analyzed in the time (least-squares fitting) and frequency domain (phasor analysis) in custom software. In vivo imaging is performed on a subcutaneous 4T1 mouse tumor-model with ICG, and a subcutaneous Fadu mouse tumor-model with an anti-EGFR Nanobody (Nb) 7D12 linked to s775z dye. Images were acquired at a height of 26 and 7cm in both ventral- and left lateral decubitus. Linearity and sensitivity are verified using a commercial reference target [4].

The capability of the tauCAM to differentiate between tumor and surrounding tissue upon FLT imaging was assessed. In mice with Fadu tumors targeted by an EGFR-targeting Nb coupled to the NIR dye s775z contrast between tumoral and surrounding tissue remains consistent over a factor of 10 of acquisition time (acquired signal) and remains consistent postmortem. Furthermore, FLT contrast was obtained in a subcutanous 4T1 mouse model between the tumor and most likely the liver as early as 1 hour after intravenous administration with ICG. It is shown that phasor processing produces FLT images with similar quality as least-squares fitting but at a fraction of the computation time. The imaging system has a demonstrated NIR fluorescence sensitivity down to 1 nM (ICG). These results are not significantly influenced by the presence of typical room lighting. Fluorescence intensity and rapid-fluorescence lifetime estimation can be overlaid on a grayscale and demonstrated at video frame rates.

This novel system is demonstrated to perform macroscale NIR fluorescence imaging with a sensitivity that is on par with conventional systems, while offering continuous simultaneous grayscale imaging without the need to turn off room lights. On top of this, the system offers time-domain capabilities which can image fluorescence lifetimes down to 300 ps. FLT microscopy (FLIM) will be performed to confirm the macroscale FLT tumor contrast.}},
  author       = {{Ingelberts, Hans and Janssen, Simone and Van Den Dries, Thomas and Lapauw, Thomas and Sahakian, Sevada and Iranian, Pooria and Kuijk, Maarten and Stroet, Marcus and Raes, Laurens and De Rooster, Hilde and Hernot, Sophie}},
  booktitle    = {{EMIM 2023, European Molecular Imaging Meeting, Abstracts}},
  language     = {{eng}},
  location     = {{Salzburg, Austria}},
  title        = {{First in vivo results for a novel macroscale time-domain fluorescence imaging system}},
  year         = {{2023}},
}