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Clinical Integration of NIR-II Fluorescence Imaging for Cancer Surgery: A Translational Evaluation of Preclinical and Intraoperative Systems
by
,
Ritesh K. Isuri
1,2,*,
Justin Williams
3,
David Rioux
4,
Paul Dorval
5,
Wendy Chung
4,
Pierre-Alix Dancer
5 and
Edward J. Delikatny
1,* 1
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Department of Physics, College of Liberal Arts and Sciences, Villanova University, Villanova, PA 19085, USA
4
Photon etc., 5795 Ave de Gaspé, #222, Montréal, QC H2S 2X3, Canada
5
Kaer Labs, 1 Rue Julien Videment, 44200 Nantes, France
*
Authors to whom correspondence should be addressed.
Cancers 2025, 17(16), 2676; https://doi.org/10.3390/cancers17162676 (registering DOI)
Submission received: 28 May 2025
/
Revised: 14 August 2025
/
Accepted: 16 August 2025
/
Published: 17 August 2025
(This article belongs to the Special Issue Application of Fluorescence Imaging in Cancer)
Simple Summary
Fluorescence imaging is increasingly being used during cancer surgery to help surgeons delineate tumors more clearly, but most current systems work in the first near-infrared (NIR-I) range, which limits how deeply light can penetrate tissue. This can make it hard to detect tumors that are just below the surface. In this study, we compared two imaging systems that operate in the second near-infrared (NIR-II) range, which allows for deeper tissue imaging with less background noise. One system is used in research labs, while the other is designed for real-time use in surgery without needing to darken the room. We tested both systems using special dye-filled models that mimic human tissue. Our findings demonstrate that the LightIR system enables NIR-II fluorescence imaging under ambient light, supporting its practical use in real-time intraoperative settings.
Abstract
Background/Objectives: Back table fluorescence imaging performed on freshly excised tissue specimens represents a critical step in fluorescence-guided surgery, enabling rapid assessment of tumor margins before final pathology. While most preclinical NIR-II imaging platforms, such as the IR VIVO (Photon, etc.), offer high-resolution and depth-sensitive imaging under controlled, enclosed conditions, they are not designed for intraoperative or point-of-care use. This study compares the IR VIVO with the LightIR system, a more compact and clinically adaptable imaging platform using the same Alizé 1.7 InGaAs detector, to evaluate whether the LightIR can offer comparable performance for back table NIR-II imaging under ambient light. Methods: Standardized QUEL phantoms containing indocyanine green (ICG) and custom agar-based tissue-mimicking phantoms loaded with IR-1048 were imaged on both systems. Imaging sensitivity, spatial resolution, and depth penetration were quantitatively assessed. LightIR was operated in pulse-mode under ambient lighting, mimicking back table or intraoperative use, while IR VIVO was operated in a fully enclosed configuration. Results: The IR VIVO system achieved high spatial resolution (~125 µm) and detected ICG concentrations as low as 30 nM in NIR-I and 300 nM in NIR-II. The LightIR system, though requiring longer exposure times, successfully resolved features down to ~250 µm and detected ICG to depths ≥4 mm. Importantly, the LightIR maintained robust NIR-II contrast under ambient lighting, aided by real-time background subtraction, and enabled clear visualization of subsurface IR-1048 targets in unshielded phantom setups, conditions relevant to back table workflows. Conclusions: LightIR offers performance comparable to the IR VIVO in terms of depth penetration and spatial resolution, while also enabling open-field NIR-II imaging without the need for a blackout enclosure. These features position the LightIR as a practical alternative for rapid, high-contrast fluorescence assessment during back table imaging. The availability of such clinical-grade systems may catalyze the development of new NIR-II fluorophores tailored for real-time surgical applications.
