Thomas Lapauw

This errata corrects the omission of a relevant reference in the main text of our recent paper [ Biomed. Opt. Express 17 , 1953 ( 2026 ) 10.1364/BOE.587556 ], clarifies a sentence in the Introduction to reflect prior work only on time-domain FLI and tumor delineation accuracy, and adds a related clarification in the Discussion. In addition, Fig. 3 has been adapted. These changes do not affect the results or conclusions of the article.

Indocyanine green (ICG) is used for tumor visualization using fluorescence-intensity imaging, but false-positive signals are common. Fluorescence-lifetime-based tumor identification may overcome this limitation by measuring the time behavior of fluorescent light. However, the optimal time point for fluorescence lifetime imaging after the intravenous administration of ICG is yet to be defined. In this paper, the in vivo time course of ICG is investigated in syngeneic tumor-bearing mice using a novel macroscopic fluorescence lifetime camera. High-dynamic-range images were generated through post-processing, investigated, and subsequently applied for time-domain intensity and lifetime image analysis. The results indicate that fluorescence lifetime imaging may provide higher accuracy in tumor identification than intensity-based imaging, but the optimal imaging time point appears to require a 24-48 hour interval after intravenous injection, similar to intensity measurements. However, earlier time points might be of interest to investigate for liver and intestinal tumors.

Correlation-Assisted Direct Time-of-Flight (CA-dToF) is demonstrated for the first time on a large 320 × 240-pixel SPAD array sensor that includes on-chip high-speed timing support circuitry. SPAD events are processed in-pixel, avoiding data communication over the array and/or storage bottlenecks. This is accomplished by sampling two orthogonal triangle waves that are synchronized with short light pulses illuminating the scene. Using small switched-capacitor circuits, exponential moving averaging (EMA) is applied to the sampled voltages, delivering two analog voltages (VQ2, VI2). These contain the phase delay, or the time of flight between the light pulse and photon’s time of arrival (ToA). Uncorrelated ambient photons and dark counts are averaged out, leaving only their associated shot noise impacting the phase precision. The QVGA camera allows for capturing depth-sense images with sub-cm precision over a 6 m range of detection, even with a small PDE of 0.7% at an 850 nm wavelength.

A 128×128-pixel current-assisted photonic sampler (CAPS) image sensor is designed for macroscale fluorescence lifetime imaging (MFLI). Current assistance is used for swift detection and time gating of the photogenerated carriers within the whole substrate. The sensor is fabricated in a commercial 350-nm CMOS process on a 15- $\mu$ m epilayer, with 19- $\mu$ m pixels and a 62% FF. The pixel features gating widths below 1 ns subject to a 42-ps standard deviation on the gate width uniformity and a 27-ps standard deviation on its temporal position. The pixel has a quantum efficiency (QE) above 40% for near-infrared (NIR) wavelengths, whereas the peak QE is 60% at 675 nm. The gate’s intrinsic decay is observed to be 280 ps, which allows for the MFLI of subnanosecond lifetime dyes. A multiexposure method has been implemented, where the pixel is nondestructively read-out multiple times—with different exposure times—after each reset. This allows for imaging with an extended dynamic range (DR) and is validated on commercial fluorescence phantoms. The MFLI capabilities are further demonstrated in a preclinical experiment.

Correlation-Assisted Direct Time-of-Flight (CA-dToF) is demonstrated for the first time with a 320×240-pixel SPAD array. SPAD triggers are processed in-pixel, avoiding data communication over the array and/or storage bottlenecks. This is accomplished by sampling two orthogonal triangle waves that are synchronized with short light pulses illuminating the scene. Using small switched-capacitor circuits, exponential-moving-averaging (EMA) is applied to the sampled voltages, delivering two analog voltages (VQ2, VI2). These contain the phase delay, or the time of flight between the light pulse and photon’s time of arrival (ToA). Uncorrelated ambient photons and dark counts are averaged out, leaving only their associated shot noise impacting the phase precision. The QVGA camera allows capturing depth-sense images with sub-cm precision over 6-m range of detection, even with a small PDE of 0.7% at 850-nm wavelength.

A video rate fluorescence lifetime (FLT) imaging system is presented featuring in-pixel lifetime calculation based on the center-of-mass of the times-of-arrival (ToA) of photons received by the single-photon avalanche diode (SPAD) of the pixel. The ToAs of photons received during a gating window placed in the decay of the returned fluorescent emission are averaged by a switched-capacitor circuit, implementing the center-of-mass method (CMM) in a compact pixel circuit. Binning of ToAs or complex time-to-digital circuits are avoided, and instead, optimal use of all received photons is achieved on a small pixel area with low communication and computational overhead. The system is validated through analytical modeling, Monte Carlo simulations, and real-world experiments using fluorophores with known lifetimes, demonstrating agreement with the analytical model and achieving accurate FLT estimations across a large range of photon counts. A dedicated QVGA (320 × 240pixel) image sensor that includes all necessary circuitry for the CMM currently reaches 10 frames per second and demonstrates the real-time FLT imaging capability of the system.

Fluorescence-guided surgery is a significant advancement in medical imaging, particularly for distinguishing malignant from healthy tissue during cancer surgery. Recent advancements in endoscopy technology and fluorescence-lifetime (FLT) imaging can provide better insight into identifying abnormal tissues during surgery than white light endoscopy imaging. Current imaging systems used in fluorescence-guided surgery are primarily designed to provide surgeons with a combined view of natural color (RGB) images and fluorescence overlays. These systems typically rely on an RGB camera, incapable of FLT imaging. Our novel approach sequentially illuminates the scene with red, green, and blue light pulses and Near Infrared (NIR) pulses, captured selectively with a single fast time-gated camera. The camera is synchronized to the pulsed illumination and positions its gate windows to capture only one of the illumination pulses; afterwards, it overlays the NIR fluorescence lifetime image on the natural color image. The VUB-ETRO team developed the tauCAMTM camera based on Current-Assisted Photonic Sampler (CAPS) image sensor technology, which intends to offer real-time FLT imaging, particularly in the NIR area. This paper presents an LED-based time-multiplexing RGB + FLT endoscopy imaging with tauCAMTM, designed to enhance visualization in real-time surgical settings. By combining RGB and FLT imaging, surgeons could receive comprehensive insights into tissue characteristics, supporting precise interventions.

In vivo fluorescence lifetime (FLT) imaging is an emerging and promising modality with the potential to provide additional biological information compared to fluorescence intensity (FI) imaging. Until now, nearly all studies evaluating the benefits of FLT imaging in vivo have been conducted using cyanine dyes. While these fluorophores are highly successful for conventional in vivo fluorescence imaging due to their unmatched brightness in the NIR-I region (700-900 nm), they might be suboptimal for FLT imaging. Indeed, NIR-I cyanines are characterized by short singlet excited-state lifetime (generally below 1 ns) making it challenging to differentiate them from tissue autofluorescence. Therefore, there is a pressing need for biocompatible fluorophores with longer FLTs. Herein, we report a novel bioconjugatable water-soluble NIR-emissive aza-BODIPY dye with extended FLT values in physiological conditions, compared to cyanine dyes (increase of 100% compared to IRDye® 800CW). The suitability of aza-BODIPY for FLT imaging when conjugated to an antibody was assessed to enhance this technology. Beyond rational design and synthesis of a long-wavelength fluorophore with attractive features for in vivo FLT imaging, this study also highlights for the first time the impact of the conjugation method on the FLT characteristics of the resulting fluorescent antibody conjugates.

This letter proposes a novel SPAD-based pixel, designed for direct time-of-flight (dToF) imaging with in-pixel averaging, which provides a promising advancement in low-power and potentially high image resolution for outdoor applications. By utilizing a laser pulse and two orthogonal sinusoidal signals, the pixel averages out the detected ambient light while accumulating the laser pulse round-trip time. A prototype pixel array was fabricated using a 180 nm CMOS process, featuring a commercial SPAD cell. By characterizing one pixel and employing a 100 klux solar emulator as an ambient light source with a fixed 40 ambient-to-signal ratio (ASR) over a 360 $^{\circ }$ phase shift, equivalent to 6 m detection range, the maximum detected accuracy error was 3.3 %, with a 5 cm precision.

There was an error in the original publication, in Equation (5)